OKPatents

Welcome to my site.
This project was developed by a former Engineer and now a patent agent assistant studding towards LLM degree. Seeing new inventions is very interesting to me. I created this site to outlines my favorite inventions along with inventions that I believe have potential.

by Watanabe, Kyoichi A.; Pankiewicz, Krzysztof W.; Krzeminski, Jacek; Nawrot, Barbara;

Several purine nucleosides containing a 2'-fluoro-2'-deoxy- .beta.-D-arabinofuranosyl moiety have been synthesized. (Watanabe et al., U.S. Pat. Nos. 4,751,221 and 4,918,179). Several nucleosides which have been synthesized have shown interesting biological activity. Specifically, 9-(2'-fluoro-2'deoxy-.beta.-D-arabinofuranosyl)-hypoxanthine (F-ara-H) has been shown to exhibit inhibitory activity against the pathogenic parasite, Leishmania tropica (Santi et al., Pharm. Res., 1985, 217). The synthetic procedure previously disclosed involved the multi-step preparation of an appropriate carbohydrate derivative which was condensed with 6-chloropurine, and the 6-purine nucleoside product was further converted after several steps into F-ara-H. This synthetic procedure was extremely laborious, time consuming, and the yield of F-ara-H was very low.

This invention discloses a superior method of preparation starting from the readily available preformed nucleosides. There has not previously been known a procedure to introduce a fluorine substituent to the C2' position of a preformed nucleoside. The procedure invented is effective not only for preparation of F-ara-H but also for 2-fluoro-arabinosyl-purine nucleosides in general in terms of steps involved, overall time required and yields of the desired nucleoside products.

SUMMARY OF THE INVENTION

The present invention provides a compound having the structure: ##STR2## wherein R.sup.1 is hydrogen, benzyl or a substituted benzyl group;

X is hydrogen, a fluoro, an amino or a substituted amino group;

Y is hydrogen, a methoxy, a methylthio, a benzylthio, an isopropyl, a chloro, an amino

Y' is an oxo or a thio group; and

Z is hydrogen, a hydroxy, a methoxy, a halogen, an amino or a substituted amino group.

The present invention also provides a process for synthesizing a compound having the structure: ##STR3## wherein R.sup.1 is hydrogen, benzyl or a substituted benzyl group;

X is hydrogen, a fluoro, an amino or a substituted amino group;

Y is hydrogen, a methoxy, a methylthio, a benzylthio, an isopropyl, a chloro, an amino or a substituted amino group;

Y' is an oxo or a thio group; and

Z is hydrogen, a hydroxy, a methoxy, a halogen, an amino or a substituted amino group;

which comprises:

(a) treating a starting compound having the structure: ##STR4## wherein R.sup.1 is hydrogen, benzyl or a substituted benzyl group;

X is hydrogen, a fluoro, an amino or a substituted amino group;

Y is hydrogen, a methoxy, a methylthio, a benzylthio, an isopropyl, a chloro, an amino or a substituted amino group;

Y' is an oxo or a thio group; and

Z is hydrogen, a hydroxy, a methoxy, a halogen, an amino or a substituted amino group;

under such conditions so as to form a compound having the structure: ##STR5## wherein R.sup.5 is triphenylmethyl, diphenyl(4-methoxyphenyl)methyl, or phenyldi(4-methoxyphenyl)methyl;

R.sup.3 and R.sup.2 are either both hydrogen or one of R.sup.3 and R.sup.2 is hydrogen and the other is triphenylmethyl, diphenyl(4-methoxyphenyl)methyl, phenyldi(4-methoxyphenyl)methyl, tetrahydropyranyl, acetyl, propanoyl, benzoyl, anisoyl, toluoyl, nitrobenzoyl, benzyl, toluyl, methoxybenzyl, or nitrobenzyl;

R.sup.1 is hydrogen, benzyl or a substituted benzyl group;

X is hydrogen, a fluoro, an amino or a substituted amino group;

Y is hydrogen, a methoxy, a methylthio, a benzylthio, an isopropyl, a chloro, an amino or a substituted amino group;

Y' is an oxo or a thio group; and

Z is hydrogen, a hydroxy, a methoxy, a halogen, an amino or a substituted amino group;

(b) treating the compound formed in step (a) under such conditions so as to form a compound having the structure: ##STR6## wherein R.sup.5 is triphenylmethyl, diphenyl(4-methoxyphenyl)methyl, or phenyldi(4-methoxyphenyl)methyl;

R.sup.3 and R.sup.2 are different wherein one of R.sup.3 and R.sup.2 is triflyl and the other is triphenylmethyl, diphenyl(4-methoxyphenyl)methyl, phenyldi(4-methoxyphenyl)methyl, tetrahydropyranyl, acetyl, propanoyl, benzoyl, anisoyl, toluoyl, nitrobenzoyl, benzyl, toluyl, methoxybenzyl, or nitrobenzyl;

R.sup.1 is hydrogen, benzyl or a substituted benzyl group;

X is hydrogen, a fluoro, an amino or a substituted amino group;

Y is hydrogen, a methoxy, a methylthio, a benzylthio, an isopropyl, a chloro, an amino or a substituted amino group;

Y' is an oxo or a thio group; and

Z is hydrogen, a hydroxy, a methoxy, a halogen, an amino or a substituted amino group;

(c) treating the compound formed in step (b) under such conditions so as to form a compound having the structure: ##STR7## wherein R.sup.5 is triphenylmethyl, diphenyl(4-methoxyphenyl)methyl, or phenyldi(4-methoxyphenyl)methyl;

R.sup.3 is triphenylmethyl, diphenyl(4-methoxyphenyl)methyl, phenyldi(4-methoxyphenyl)methyl, tetrahydropyranyl, acetyl, propanoyl, benzoyl, anisoyl, toluoyl, nitrobenzoyl, benzyl, toluyl, methoxybenzyl, or nitrobenzyl;

R.sup.1 is hydrogen, benzyl or a substituted benzyl group;

X is hydrogen, a fluoro, an amino or a substituted amino group;

Y is hydrogen, a methoxy, a methylthio, a benzylthio, an isopropyl, a chloro, an amino or a substituted amino group;

Y' is an oxo or a thio group; and

Z is hydrogen, a hydroxy, a methoxy, a halogen, an amino or a substituted amino group; and

(d) treating the compound formed in step (c) under such conditions so as to form a compound having the structure: ##STR8## wherein R.sup.1 is hydrogen, benzyl or a substituted benzyl group;

X is hydrogen, a fluoro, an amino or a substituted amino group;

Y is hydrogen, a methoxy, a methylthio, a benzylthio, an isopropyl, a chloro, an amino or a substituted amino group;

Y is an oxo or a thio group; and

Z is hydrogen, a hydroxy, a methoxy, a halogen, an amino or a substituted amino group;

The present invention also provides a compound having the structure: ##STR9## wherein R.sup.5 is triphenylmethyl, diphenyl(4-methoxyphenyl)methyl, or phenyldi(4 -methoxyphenyl)methyl;

R.sup.3 and R.sup.2 are either the same or different and are hydrogen, triflyl, triphenylmethyl, diphenyl(4-methoxyphenyl)methyl, phenyldi(4-methoxyphenyl)methyl, tetrahydropyranyl, acetyl, propanoyl, benzoyl, anisoyl, toluoyl, nitrobenzoyl, benzyl, toluyl, methoxybenzyl, or nitrobenzyl;

X is hydrogen, a fluoro, an amino or a substituted amino group;

Y is hydrogen, a methoxy, a methylthio, a benzylthio, an isopropyl, a chloro, an amino or a substituted amino group; and

Y' is an oxo of a thio group; and

Z is hydrogen, a hydroxy, a methoxy, a halogen, an amino or a substituted amino group;

The present invention also provides a compound having the structure: ##STR10## wherein R.sup.5 is triphenylmethyl, diphenyl(4-methoxyphenyl)methyl, or phenyldi(4-methoxyphenyl)methyl;

R.sup.3 is hydrogen, triflyl, triphenylmethyl, diphenyl(4-methoxyphenyl)methyl, phenyldi(4-methoxyphenyl)methyl, tetrahydropyranyl, acetyl, propanoyl, benzoyl, anisoyl, toluoyl, nitrobenzoyl, benzyl, toluyl, methoxybenzyl, or nitrobenzyl;

R.sup.1 is hydrogen, benzyl or a substituted benzyl group;

X is hydrogen, a flouro, an amino or a substituted amino;

Y is hydrogen, a methoxy, a methylthio, a benzylthio, a methylethyl, a chloro, an amino or a substituted amino;

Y' is an oxo or a thio group; and

Z is hydrogen, a hydroxy, a methoxy, a halogen, an amino or a substituted amino;

BRIEF DESCRIPTION OF THE FIGURES

FIG. 1. This figure represents a scheme of two methods of synthesis of 2'-"up" fluorinated nucleosides starting with the preformed nucleoside, 1-benzylinosine. R represents either an acetyl group (a) or a trityl group (b). The 2'-"up" fluorinated nucleosides may be synthesized by either protecting the 3' and 5' positions followed by triflylation and then fluoridation with TASF or directly treating a 3' and 5' trityl-protected nucleoside with DAST.

DETAILED DESCRIPTION OF THE INVENTION

The present invention provides a compound having the structure: ##STR11## wherein R.sup.1 is hydrogen, benzyl or a substituted benzyl group;

X is hydrogen, a fluoro, an amino or a substituted amino group;

Y is hydrogen, a methoxy, a methylthio, a benzylthio, an isopropyl, a chloro, an amino or a substituted amino group; and

Y' is an oxo or a thio group; and

Z is hydrogen, a hydroxy, a methoxy, a halogen, an amino or a substituted amino group.

Compounds having the above-identified structure, although not limited to the following compounds, may be selected from the group consisting of:

9-(2'deoxy-2-fluoro-.beta.-D-arabinofuranosyl)purine,

9-(2'deoxy-2-fluoro-.beta.-D-arabinofuranosyl)-6-chloropurine,

9-(2'deoxy-2-fluoro-.beta.-D-arabinofuranosyl)-6-thiopurine,

9-(2'deoxy-2-fluoro-.beta.-D-arabinofuranosyl)-6-methylthiopurine,

9-(2'deoxy-2-fluoro-.beta.-D-arabinofuranosyl)-6-aminomethylpurine,

9-(2'deoxy-2-fluoro-.beta.-D-arabinofuranosyl)-6-dimethylaminopurine,

9-(2'deoxy-2-fluoro-.beta.-D-arabinofuranosyl)-2-aminopurine,

9-(2'deoxy-2-fluoro-.beta.-D-arabinofuranosyl)-2-acetamidopurine,

9-(2'deoxy-2-fluoro-.beta.-D-arabinofuranosyl)-2-benzamidopurine,

9-(2'deoxy-2-fluoro-.beta.-D-arabinofuranosyl)-2-isobytanamidopurine,

9-(2'deoxy-2-fluoro-.beta.-D-arabinofuranosyl)-2,6-diaminopurine,

9-(2'deoxy-2-fluoro-.beta.-D-arabinofuranosyl)-2,6-diacetamidopurine,

9-(2'deoxy-2-fluoro-.beta.-D-arabinofuranosyl)-2,6-dibenzamidopurine,

9-(2'deoxy-2-fluoro-.beta.-D-arabinofuranosyl)-2,6-diisobutanamidopurine,

9-(2'deoxy-2-fluoro-.beta.-D-arabinofuranosyl)-2-amino-6-chloropurine,

9-(2'deoxy-2-fluoro-.beta.-D-arabinofuranosyl)-2-amino-6-thiopurine,

9-(2'deoxy-2-fluoro-.beta.-D-arabinofuranosyl)-2-amino-6-methylthiopurine,

9-(2'deoxy-2-fluoro-.beta.-D-arabinofuranosyl)-2-fluoropurine,

9-(2'deoxy-2-fluoro-.beta.-D-arabinofuranosyl)-2-fluoro-6-thiopurine,

9-(2'deoxy-2-fluoro-.beta.-D-arabinofuranosyl)-2-fluoro-6-methylthiopurine,

9-(2'deoxy-2-fluoro-.beta.-D-arabinofuranosyl)-2-fluoro-6-aminomethylpurine

9-(2'deoxy-2-fluoro-.beta.-D-arabinofuranosyl)-2-fluoro-6-dimethylaminopuri ne,

9-(2'deoxy-2-fluoro-.beta.-D-arabinofuranosyl)adenine,

9-(2'deoxy-2-fluoro-.beta.-D-arabinofuranosyl)-2-fluoroadenine,

9-(2'deoxy-2-fluoro-.beta.-D-arabinofuranosyl)-2-acetamidoadenine,

9-(2'deoxy-2-fluoro-.beta.-D-arabinofuranosyl)-2-benzamidoadenine,

9-(2'deoxy-2-fluoro-.beta.-D-arabinofuranosyl)-2-isobytanamidoadenine,

9-(2'deoxy-2-fluoro-.beta.-D-arabinofuranosyl)-N.sup.6 -trityladenine,

9-(2'deoxy-2-fluoro-.beta.-D-arabinofuranosyl)-N.sup.6 -acetyladenine,

9-(2'deoxy-2-fluoro-.beta.-D-arabinofuranosyl)-N.sup.6 -benzoyladenine,

9-(2'deoxy-2'-fluoro-.beta.-D-arabinofuranosyl)thioguanine,

9-(2'deoxy-2'-fluoro-.beta.-D-arabinofuranosyl)-2-fluorohypoxanthine,

9-(2'deoxy-2'-fluoro-.beta.-D-arabinofuranosyl)hypoxanthine, or

9-(2'deoxy-2'-fluoro-.beta.-D-arabinofuranosyl)guanine.

The present invention also provides a method for synthesizing a compound having the structure: ##STR12## wherein R.sup.1 is hydrogen, benzyl or a substituted benzyl group;

X is hydrogen, a fluoro, an amino or a substituted amino group;

Y is hydrogen, a methoxy, a methylthio, a benzylthio, an isopropyl, a chloro, an amino or a substituted amino group;

Y' is an oxo or a thio group; and

Z is hydrogen, a hydroxy, a methoxy, a halogen, an amino or a substituted amino group;

which comprises:

(a) treating a starting compound having the structure: ##STR13## wherein R.sup.1 is hydrogen, benzyl or a substituted benzyl group;

X is hydrogen, a fluoro, an amino or a substituted amino group;

Y is hydrogen, a methoxy, a methylthio, a benzylthio, an isopropyl, a chloro, an amino or a substituted amino group;

Y' is an oxo or a thio gorup; and

Z is hydrogen, a hydroxy, a methoxy, a halogen, an amino or a substituted amino group;

under such conditions so as to form a compound having the structure: ##STR14## wherein R.sup.5 is triphenylmethyl, diphenyl(4-methoxyphenyl)methyl, or phenyldi(4-methoxyphenyl)methyl;

R.sup.3 and R.sup.2 are either both hydrogen or one of R.sup.3 and R.sup.2 is hydrogen and the other is triphenylmethyl, diphenyl(4-methoxyphenyl)methyl, phenyldi(4-methoxyphenyl)methyl, tetrahydropyranyl, acetyl, propanoyl, benzoyl, anisoyl, toluoyl, nitrobenzoyl, benzyl, toluyl, methoxybenzyl, or nitrobenzyl;

R.sup.1 is hydrogen, benzyl or a substituted benzyl group;

X is hydrogen, a fluoro, an amino or a substituted amino group;

Y is hydrogen, a methoxy, a methylthio, a benzylthio, an isopropyl, a chloro, an amino or a substituted amino group;

Y' is an oxo or a thio group; and

Z is hydrogen, a hydroxy, a methoxy, a halogen, an amino or a substituted amino group;

(b) treating the compound formed in step (a) under such conditions so as to form a compound having the structure: ##STR15## wherein R.sup.5 is triphenylmethyl, diphenyl(4-methoxyphenyl)-methyl, or phenyldi(4-methoxyphenyl)methyl;

R.sup.3 and R.sup.2 are different wherein one of R.sup.3 and R.sup.2 is triflyl and the other is triphenylmethyl, diphenyl(4-methoxyphenyl)methyl, phenyldi(4-methoxyphenyl)methyl, tetrahydropyranyl, acetyl, propanoyl, benzoyl, anisoyl, toluoyl, nitrobenzoyl, benzyl, toluyl, methoxybenzyl, or nitrobenzyl;

R.sup.1 is hydrogen, benzyl or a substituted benzyl group;

X is hydrogen, a fluoro, an amino or a substituted amino group;

Y is hydrogen, a methoxy, a methylthio, a benzylthio, an isopropyl, a chloro, an amino or a substituted amino group;

Y' is an oxo or a thio group; and

Z is hydrogen, a hydroxy, a methoxy, a halogen, an amino or a substituted amino group;

(c) treating the compound formed in step (b) under such conditions so as to form a compound having the structure: ##STR16## wherein R.sup.5 is triphenylmethyl, diphenyl(4-methoxyphenyl)methyl, or phenyldi(4-methoxyphenyl)methyl;

R.sup.3 is triphenylmethyl, diphenyl (4-methoxyphenyl)methyl, phenyldi(4-methoxyphenyl)methyl, tetrahydropyranyl, acetyl, propanoyl, benzoyl, anisoyl, toluoyl, nitrobenzoyl, benzyl, toluyl, methoxybenzyl, or nitrobenzyl;

R.sup.1 is hydrogen, benzyl or a substituted benzyl group;

X is hydrogen, a fluoro, an amino or a substituted amino group;

Y is hydrogen, a methoxy, a methylthio, a benzylthio, an isopropyl, a chloro, an amino or a substituted amino group;

Y' is an oxo or a thio group; and

Z is hydrogen, a hydroxy, a methoxy, a halogen, an amino or a substituted amino group; and

(d) treating the compound formed in step (c) under such conditions so as to form a compound having the structure: ##STR17## wherein R.sup.1 is hydrogen, benzyl or a substituted benzyl group;

X is hydrogen, a fluoro, an amino or a substituted amino group;

Y is hydrogen, a methoxy, a methylthio, a benzylthio, an isopropyl, a chloro, an amino or a substituted amino group;

Y' is an oxo or a thio group; and

Z is hydrogen, a hydroxy, a methoxy, a halogen, an amino or a substituted amino group;

In one embodiment of the present invention, the treating in step (a) comprises contacting the starting compound of step (a) with a suitable amount of trityl chloride or a related protecting group in the presence of an organic solvent. ("trityl" as used herein is triphenylmethyl). The treating is performed at room temperature for an effective amount of time to promote reaction. The suitable amount of trityl chloride is enough trityl chloride to promote reaction. The preferred organic solvent is pyridine.

In another embodiment, the treating in step (a) comprises contacting the compound of step (a) with a strong organic base and a suitable amount of trityl cloride or a related protecting group in an organic solvent. In the preferred embodiment, the treating is performed at a temperature range of 70.degree. to 80.degree. C. The strong organic base is preferably 4-dimethylaminopyridine. The preferred organic solvent is pyridine. The suitable amount of trityl chloride is enough trityl chloride to promote reaction.

The treating in step (a) is not limited to contacting the starting compound of step (a) with trityl chloride. The treating may also comprise contacting the starting compound of step (a) with other protecting groups such as diphenyl(4-methoxyphenyl)methyl, phenyldi(4-methoxyphenyl)methyl, tetahydropyranyl acetyl, propanoyl, benzoyl, anisoyl, toluoyl, nitrobenzoyl, benzyl, toluyl, methoxybenzyl, or nitrobenzyl.

In one embodiment, the treating in step (b) comprises contacting the compound formed in step (a) with dibutylin oxide under heat to form a residue, contacting the residue so formed with a suitable amount of triflyl chloride or a related triflylating agent to form a solution, and treating the solution so formed with acetic anhydride. The suitable amount of triflyl chloride is enough triflyl chloride to promote reaction. ("triflyl" as used herein is trifluoromethyl-sulfonyl).

In another embodiment, the treating in step (b) comprises contacting the compound formed in step (a) with 4-dimethylaminopyridine, triethylamine in methylene chloride and a suitable amount of triflyl chloride or related triflylating agent. The suitable amount of triflyl chloride is enough triflyl chloride to promote reaction.

The treating in step (c) comprises contacting the compound formed in step (b) with a suitable amount of a fluorinating agent. The fluorinating agent may be but is not limited to the following: potassium fluoride in dimethylformamide, tetrabutyl ammonium fluoride in dimethylformamide, Amberlyst 26 (F.sup.- form) in acetone, or tris(dimethylamino)-sulfur(trimethylsilyl)-difluoride (TASF) in methylene chloride. In the above process, the preferred fluorinating agent is tris(dimethyamino)-sulfur-(trimethylsilyl)difluoride (TASF) in methylene chloride. The suitable amount of the fluorination agent is enough fluorinating agent to promote reaction. The treating is preferably performed in an argon atmosphere at a temperature of about -70.degree. C.

The treating in step (d) comprises contacting the compound formed in step (c) with a suitable amount of an acid. The preferable acid is trifluoracetic acid. The treating is preferably performed in an argon atmosphere at a temperature of about -25.degree. C. The suitable amount of acid is enough acid to promote reaction.

The present invention also provides another process for synthesizing the compound above which comprises

(a) treating a starting compound having the structure: ##STR18## wherein R.sup.1 is hydrogen, benzyl or a substituted benzyl group;

X is hydrogen, a fluoro, an amino or a substituted amino group;

Y is hydrogen, a methoxy, a methylthio, a benzylthio, an isopropyl, a chloro, an amino or a substituted amino group;

Y' is an oxo or a thio group; and

Z is hydrogen, a hydroxy, a methoxy, a halogen, an amino or a substituted amino group;

under such conditions so as to form a compound having the structure: ##STR19## wherein R.sup.5 is triphenylmethyl, diphenyl(4-methoxyphenyl)methyl, or phenyldi(4 -methoxyphenyl)methyl;

R.sup.3 and R.sup.2 are different, wherein one of R.sup.3 and R.sup.2 is hydrogen and the other is triphenylmethyl, diphenyl(4-methoxyphenyl)methyl, phenyldi(4-methoxyphenyl)methyl, tetrahydropyranyl, acetyl, propanoyl, benzoyl, anisoyl, toluoyl, nitrobenzoyl, benzyl, toluyl, methoxybenzyl, or nitrobenzyl;

R.sup.1 is hydrogen, benzyl or a substituted benzyl group;

X is hydrogen, a flouro, an amino or a substituted amino group;

Y is hydrogen, a methoxy, a methylthio, a benzylthio, a methylethyl, a chloro, an amino or a substituted amino group;

Y' is an oxo or a thio group; and

Z is hydrogen, a hydroxy, a methoxy, a halogen, an amino or a substituted amino group;

(b) treating the compound formed in step (a) under such conditions so as to form a compound having the structure: ##STR20## wherein R.sup.5 is triphenylmethyl, diphenyl(4-methoxyphenyl)methyl, or phenyldi(4-methoxyphenyl)methyl;

R.sup.3 is triphenylmethyl, diphenyl(4-methoxyphenyl)methyl, phenyldi(4-methoxyphenyl)methyl, tetrahydropyranyl, acetyl, propanoyl, benzoyl, anisoyl, toluoyl, nitrobenzoyl, benzyl, toluyl, methoxybenzyl, or nitrobenzyl;

R.sup.1 is hydrogen, benzyl or a substituted benzyl group;

X is hydrogen, a fluoro, an amino or a substituted amino group;

Y is hydrogen, a methoxy, a methylthio, a benzylthio, an isopropyl, a chloro, an amino or a substituted amino group;

Y' is an oxo or a thio group; and

Z is hydrogen, a hydroxy, a methoxy, a halogen, an amino or a substituted amino group; and

(c) treating the compound formed in step (b) under such conditions so as to form a compound having the structure: ##STR21## wherein R.sup.1 is hydrogen, benzyl or a substituted benzyl;

X is hydrogen, a flouro, an amino or a substituted amino group;

Y is hydrogen, a methoxy, a methylthio, a benzylthio, a methylethyl, a chloro, an amino or a substituted amino group;

Y' is an oxo or a thio group; and

Z is hydrogen, a hydroxy, a methoxy, a halogen, an amino or a substituted amino group;

The above process is the preferred process of synthesis.

The treating in step (a) comprises contacting the starting compound of step (a) with a strong organic base and a suitable amount of trityl cloride or a substitute derivative thereof in an organic solvent. The treating is preferable performed at a temperature range of 70.degree. to 80.degree. C. The strong organic base is preferably 4-dimethylaminopyridine and the organic solvent is preferably pyridine. The suitable amount of trityl chloride is enough trityl chloride to promote reaction.

The treating in step (b) comprises contacting the compound formed in step (a) with a suitable amount of diethylamino-sulfurtrifluoride (DAST) or a related fluorinating agent. The treating is best performed at a temperature below -50.degree. C. The suitable amount of diethylamino-sulfurtrifluoride (DAST) is enough diethylamino-sulfurtrifluoride (DAST) to promote reaction.

The treating in step (c) comprises contacting the compound formed in step (b) with a suitable amount of an acid. The acid is preferably trifluoracetic acid. The suitable amount of the acid is enough acid to promote reaction. The treating is preferably performed in an argon atmosphere at a temperature of about -25.degree. C.

The present invention also provides a compound having the structure: ##STR22## wherein R.sup.5 is triphenylmethyl, diphenyl(4-methoxyphenyl)methyl, or phenyldi(4-methoxyphenyl)methyl;

R.sup.3 and R.sup.2 are either the same or different and are hydrogen, triflyl, triphenylmethyl, diphenyl(4-methoxyphenyl)methyl, phenyldi(4-methoxyphenyl)methyl, tetrahydropyranyl, acetyl, propanoyl, benzoyl, anisoyl, toluoyl, nitrobenzoyl, benzyl, toluyl, methoxybenzyl, or nitrobenzyl;

X is hydrogen, a fluoro, an amino or a substituted amino group;

Y is hydrogen, a methoxy, a methylthio, a benzylthio, an isopropyl, a chloro, an amino or a substituted amino group; and

Y' is an oxo of a thio group; and

Z is hydrogen, a hydroxy, a methoxy, a halogen, an amino or a substituted amino group;

Compounds having the above-identified structure, although not limited to the following compounds, may be selected from the group consisting of:

9-(5'-O-trityl-.beta.-D-ribofuranosyl)purine,

9-(5'-O-trityl-.beta.-D-ribofuranosyl)-6-chloropurine,

9-(5'-O-trityl-.beta.-D-ribofuranosyl)-6-aminomethylpurine,

9-(5'-O-trityl-.beta.-D-ribofuranosyl)-2-aminopurine,

9-(5'-O-trityl-.beta.-D-ribofuranosyl)-2-acetamidopurine,

9-(5'-O-trityl-.beta.-D-ribofuranosyl)-2-benzamidopurine,

9-(5'-O-trityl-.beta.-D-ribofuranosyl)-2-isobutanamidopurine,

9-(5'-O-trityl-.beta.-D-ribofuranosyl)-2,6-diaminopurine,

9-(5'-O-trityl-.beta.-D-ribofuranosyl)-2,6-diacetamidopurine,

9-(5'-O-trityl-.beta.-D-ribofuranosyl)-2,6-diabenzamidopurine,

9-(5'-O-trityl-.beta.-D-ribofuranosyl)-2,6-diisobutanmidopurine,

9-(5'-O-trityl-.beta.-D-ribofuranosyl)-2-amino-6-chloropurine,

9-(5'-O-trityl-.beta.-D-ribofuranosyl)-2-amino-6-thiopurine,

9-(5'-O-trityl-.beta.-D-ribofuranosyl)-2-amino-6-aminomethylthiopurine,

9-(5'-O-trityl-.beta.-D-ribofuranosyl)-2-fluoropurine,

9-(5'-O-trityl-.beta.-D-ribofuranosyl)-2-fluoro-6-thiopurine,

9-(5'-O-trityl-.beta.-D-ribofuranosyl)-2-fluoro-6-methylthiopurine,

9-(5'-O-trityl-.beta.-D-ribofuranosyl)-2-fluoro-6-dimethylaminopurine,

9-(5'-O-trityl-.beta.-D-ribofuranosyl)-2-fluoroadenine,

9-(3'-O-acetyl-2'-O-triflyl-5'-O-trityl-.beta.-D-ribofuranosyl)purine,

9-(3'-O-acetyl-2'-O-triflyl-5'-O-trityl-.beta.-D-ribofuranosyl)-6-chloropur ine,

9-(3'-O-acetyl-2'-O-triflyl-5'-O-trityl-.beta.-D-ribofuranosyl)-6-thiopurin e,

9-(3'-O-acetyl-2'-O-triflyl-5'-O-trityl-.beta.-D-ribofuranosyl)-6-methylthi opurine,

9-(3'-O-acetyl-2'-O-triflyl-5'-O-trityl-.beta.-D-ribofuranosyl)-6-aminometh ylpurine,

9-(3'-O-acetyl-2'-O-triflyl-5'-O-trityl-.beta.-D-ribofuranosyl)-6-dimethyla minopurine,

9-(3'-O-acetyl-2'-O-triflyl-5'-O-trityl-.beta.-D-ribofuranosyl)-2-aminopuri ne,

9-(3'-O-acetyl-2'-O-triflyl-5'-O-trityl-.beta.-D-ribofuranosyl)-2-acetamido purine,

9-(3'-O-acetyl-2'-O-triflyl-5'-O-trityl-.beta.-D-ribofuranosyl)-2-benzamido purine,

9-(3'-O-acetyl-2'-O-triflyl-5'-O-trityl-.beta.-D-ribofuranosyl)-2-isobutana idopurine,

9-(3'-O-acetyl-2'-O-triflyl-5'-O-trityl-.beta.-D-ribofuranosyl)-2,6-diamino purine,

9-(3'-O-acetyl-2'-O-triflyl-5'-O-trityl-.beta.-D-ribofuranosyl)-2,6-diaceta midopurine,

9-(3'-O-acetyl-2'-O-triflyl-5'-O-trityl-.beta.-D-ribofuranosyl)-2,6-dibenza midopurine,

9-(3'-O-acetyl-2'-O-triflyl-5'-O-trityl-.beta.-D-ribofuranosyl)-2,6-diisobu tanamidopurine,

9-(3'-O-acetyl-2'-O-triflyl-5'-O-trityl-.beta.-D-ribofuranosyl)-2-amino-6-c hloropurine,

9-(3'-O-acetyl-2'-O-triflyl-5'-O-trityl-.beta.-D-ribofuranosyl)-2-amino-6-t hiopurine,

9-(3'-O-acetyl-2'-O-triflyl-5'-O-trityl-.beta.-D-ribofuranosyl)-2-amino-6-m ethylthiopurine,

9-(3'-O-acetyl-2'-O-triflyl-5'-O-trityl-.beta.-D-ribofuranosyl)-2-fluoropur ine,

9-(3'-O-acetyl-2'-O-triflyl-5'-O-trityl-.beta.-D-ribofuranosyl)-2-fluoro-6- thiopurine,

9-(3'-O-acetyl-2'-O-triflyl-5'-O-trityl-.beta.-D-ribofuranosyl)-2-fluoro-6- methylthiopurine,

9-(3'-O-acetyl-2'-O-triflyl-5'-O-trityl-.beta.-D-ribofuranosyl)-2-fluoro-6- aminomethylpurine,

9-(3'-O-acetyl-2'-O-triflyl-5'-O-trityl-.beta.-D-ribofuranosyl)-2-fluoro-6- dimethylaminopurine,

9-(3'-O-acetyl-2'-O-triflyl-5'-O-trityl-.beta.-D-ribofuranosyl)-N.sup.6 -acetyladenine,

9-(3'-O-acetyl-2'-O-triflyl-5'-O-trityl-.beta.-D-ribofuranosyl)-N.sup.6 -benzoyladenine,

9-(3'-O-acetyl-2'-O-triflyl-5'-O-trityl-.beta.-D-ribofuranosyl)-N.sup.6 -trityladenine,

9-(3'-O-acetyl-2'-O-triflyl-5'-O-trityl-.beta.-D-ribofuranosyl)-2-fluoroade nine,

9-(2',5'-di-O-trityl-.beta.-D-ribofuranosyl)purine,

9-(2',5'-di-O-trityl-.beta.-D-ribofuranosyl)-6-thiopurine,

9-(2',5'-di-O-trityl-.beta.-D-ribofuranosyl)-6-methylthiopurine,

9-(2',5'-di-O-trityl-.beta.-D-ribofuranosyl)-6-aminomethylpurine,

9-(2',5'-di-O-trityl-.beta.-D-ribofuranosyl)-6-dimethylaminopurine,

9-(2',5'-di-O-trityl-.beta.-D-ribofuranosyl)-2-aminopurine,

9-(2',5'-di-O-trityl-.beta.-D-ribofuranosyl)-2-acetamidopurine

9-(2',5'-di-O-trityl-.beta.-D-ribofuranosyl)-2-benzamidopurine

9-(2',5'-di-O-trityl-.beta.-D-ribofuranosyl)-2-isobutanamidopurine

9-(2',5'-di-O-trityl-.beta.-D-ribofuranosyl)-2,6-diaminopurine,

9-(2',5'-di-O-trityl-.beta.-D-ribofuranosyl)-2,6-diacetamidopurine,

9-(2',5'-di-O-trityl-.beta.-D-ribofuranosyl)-2,6-dibenzamidopurine,

9-(2',5'-di-O-trityl-.beta.-D-ribofuranosyl)-2,6-diisobutanamidopurine,

9-(2',5'-di-O-trityl-.beta.-D-ribofuranosyl)-2-amino-6-chloropurine,

9-(2',5'-di-O-trityl-.beta.-D-ribofuranosyl)-2-amino-6-thiopurine,

9-(2',5'-di-O-trityl-.beta.-D-ribofuranosyl)-2-amino-6-methylthiopurine,

9-(2',5'-di-O-trityl-.beta.-D-ribofuranosyl)-2-fluoropurine,

9-(2',5'-di-O-trityl-.beta.-D-ribofuranosyl)-2-fluoro-6-thiopurine,

9-(2',5'-di-O-trityl-.beta.-D-ribofuranosyl)-2-fluoro-6-methylthiopurine,

9-(2',5'-di-O-trityl-.beta.-D-ribofuranosyl)-2-fluoro-6-aminomethylpurine,

9-(2',5'-di-O-trityl-.beta.-D-ribofuranosyl)-2-fluoro-6-dimethylaminopurine

9-(2',5'-di-O-trityl-.beta.-D-ribofuranosyl)-N.sup.6 -triyladenine,

9-(2',5'-di-O-trityl-.beta.-D-ribofuranosyl)-N.sup.6 -acetyladenine,

9-(2',5'-di-O-trityl-.beta.-D-ribofuranosyl)-N.sup.6 -benzoyladenine,

9-(2',5'-di-O-trityl-.beta.-D-ribofuranosyl)-2-fluoroadenine,

9-(3',5'-di-O-trityl-.beta.-D-ribofuranosyl)purine,

9-(3',5'-di-O-trityl-.beta.-D-ribofuranosyl)-6-chloropurine,

9-(3',5'-di-O-trityl-.beta.-D-ribofuranosyl)-6-thiopurine,

9-(3',5'-di-O-trityl-.beta.-D-ribofuranosyl)-6-methylthiopurine,

9-(3',5'-di-O-trityl-.beta.-D-ribofuranosyl)-6-aminomethylpurine,

9-(3',5'-di-O-trityl-.beta.-D-ribofuranosyl)-6-dimethylaminopurine,

9-(3',5'-di-O-trityl-.beta.-D-ribofuranosyl)-2-aminopurine,

9-(3',5'-di-O-trityl-.beta.-D-ribofuranosyl)-2-acetamidopurine,

9-(3',5'-di-O-trityl-.beta.-D-ribofuranosyl)-2-benzamidopurine,

9-(3',5'-di-O-trityl-.beta.-D-ribofuranosyl)-2-isobutanamidopurine,

9-(3',5'-di-O-trityl-.beta.-D-ribofuranosyl)-2,6-diaminopurine,

9-(3',5'-di-O-trityl-.beta.-D-ribofuranosyl)-2,6-dibenzamidopurine,

9-(3',5'-di-O-trityl-.beta.-D-ribofuranosyl)-2,6-diisobutanamidopurine,

9-(3',5'-di-O-trityl-.beta.-D-ribofuranosyl)-2-amino-6-chloropurine,

9-(3',5'-di-O-trityl-.beta.-D-ribofuranosyl)-2-amino-6-thiopurine,

9-(3',5'-di-O-trityl-.beta.-D-ribofuranosyl)-2-amino-6-methylthiopurine,

9-(3',5'-di-O-trityl-.beta.-D-ribofuranosyl)-2-fluoropurine,

9-(3',5'-di-O-trityl-.beta.-D-ribofuranosyl)-2-fluoro-6-thiopurine,

9-(3',5'-di-O-trityl-.beta.-D-ribofuranosyl)-2-fluoro-6-methylthiopurine,

9-(3',5'-di-O-trityl-.beta.-D-ribofuranosyl)-2-fluoro-6-aminomethylpurine,

9-(3',5'-di-O-trityl-.beta.-D-ribofuranosyl)-2-fluoro-6-dimethylaminopurine

9-(3',5'-di-O-trityl-.beta.-D-ribofuranosyl)-N.sup.6 -trityladenine,

9-(3',5'-di-O-trityl-.beta.-D-ribofuranosyl)-N.sup.6 -acetyladenine,

9-(3',5'-di-O-trityl-.beta.-D-ribofuranosyl)-N.sup.6 -benzoyladenine,

9-(3',5'-di-O-trityl-.beta.-D-ribofuranosyl)-N.sup.2 -trityladenine,

9-(3',5'-di-O-trityl-.beta.-D-ribofuranosyl)-N.sup.2 -acetyladenine,

9-(3',5'-di-O-trityl-.beta.-D-ribofuranosyl)-N.sup.2 -benzoyladenine,

9-(3',5'-di-O-trityl-.beta.-D-ribofuranosyl)-2-fluoroadenine,

9-(2'-O-triflyl-3',5'-di-O-trityl-.beta.-D-ribofuranosyl)-N.sup.2 -trityl-6-thiopurine,

9-(2'-O-triflyl-3',5'-di-O-trityl-.beta.-D-ribofuranosyl)purine,

9-(2'-O-triflyl-3',5'-di-O-trityl-.beta.-D-ribofuranosyl)-6-chloropurine,

9-(2'-O-triflyl-3',5'-di-O-trityl-.beta.-D-ribofuranosyl)-6-thiopurine,

9-(2'-O-triflyl-3',5'-di-O-trityl-.beta.-D-ribofuranosyl)-6-methylthiopurin e,

9-(2'-O-triflyl-3',5'-di-O-trityl-.beta.-D-ribofuranosyl)-6-aminomethylpuri ne,

9-(2'-O-triflyl-3',5'-di-O-trityl-.beta.-D-ribofuranosyl)-6-dimethylaminopu rine,

9-(2'-O-triflyl-3',5'-di-O-trityl-.beta.-D-ribofuranosyl)-6-aminopurine,

9-(2'-O-triflyl-3',5'-di-O-trityl-.beta.-D-ribofuranosyl)-2-acetamidopurine

9-(2'-O-triflyl-3',5'-di-O-trityl-.beta.-D-ribofuranosyl)-2-benzamidopurine

9-(2'-O-triflyl-3',5'-di-O-trityl-.beta.-D-ribofuranosyl)-2-isobutanamidopu rine,

9-(2'-O-triflyl-3',5'-di-O-trityl-.beta.-D-ribofuranosyl)-2,6-diaminopurine

9-(2'-O-triflyl-3',5'-di-O-trityl-.beta.-D-ribofuranosyl)-2,6-diacetamidopu rine,

9-(2'-O-triflyl-3',5'-di-O-trityl-.beta.-D-ribofuranosyl)-2,6-dibenzamidopu rine,

9-(2'-O-triflyl-3',5'-di-O-trityl-.beta.-D-ribofuranosyl)-2,6-diisobutanami dopurine,

9-(2'-O-triflyl-3',5'-di-O-trityl-.beta.-D-ribofuranosyl)-2-amino-6-chlorop urine,

9-(2'-O-triflyl-3',5'-di-O-trityl-.beta.-D-ribofuranosyl)-2-amino-6-thiopur ine,

9-(2'-O-triflyl-3',5'-di-O-trityl-.beta.-D-ribofuranosyl)-2amino -6-methylthiopurine,

9-(2'-O-triflyl-3',5'-di-O-trityl-.beta.-D-ribofuranosyl)-2-fluoropurine,

9-(2'-O-triflyl-3',5'-di-O-trityl-.beta.-D-ribofuranosyl)-2-fluoro-6-thiopu rine,

9-(2'-O-triflyl-3',5'-di-O-trityl-.beta.-D-ribofuranosyl)-2-fluoro -6-methylthiopurine,

9-(2'-O-triflyl-3',5'-di-O-trityl-.beta.-D-ribofuranosyl)-2-fluoro -6-aminomethylpurine,

9-(2'-O-triflyl-3',5'-di-O-trityl-.beta.-D-ribofuranosyl)-2-fluoro-6-dimeth ylaminopurine,

9-(2'-O-triflyl-3',5'-di-O-trityl-.beta.-D-ribofuranosyl)-N.sup.6 -trityladenine,

9-(2'-O-triflyl-3',5'-di-O-trityl-.beta.-D-ribofuranosyl)-N.sup.6 -acetyladenine,

9-(2'-O-triflyl-3',5'-di-O-trityl-.beta.-D-ribofuranosyl)-N.sup.6 -benzoyladenine,

9-(2'-O-triflyl-3',5'-di-O-trityl-.beta.-D-ribofuranosyl)-2-fluoroadenine,

9-(3'-O-triflyl-2',5'-di-O-trityl-.beta.-D-ribofuranosyl)purine,

9-(3'-O-triflyl-2',5'-di-O-trityl-.beta.-D-ribofuranosyl)-6-chloropurine,

9-(3'-O-triflyl-2',5'-di-O-trityl-.beta.-D-ribofuranosyl)-6-thiopurine,

9-(3'-O-triflyl-2',5'-di-O-trityl-.beta.-D-ribofuranosyl)-6-methylthiopurin e,

9-(3'-O-triflyl-2',5'-di-O-trityl-.beta.-D-ribofuranosyl)-6-aminomethylpuri ne,

9-(3'-O-triflyl-2',5'-di-O-trityl-.beta.-D-ribofuranosyl)-6-dimethylaminopu rine,

9-(3'-O-triflyl-2',5'-di-O-trityl-.beta.-D-ribofuranosyl)-6-aminopurine,

9-(3'-O-triflyl-2',5'-di-O-trityl-.beta.-D-ribofuranosyl)-6-diaminopurine,

9-(3'-O-triflyl-2',5'-di-O-trityl-.beta.-D-ribofuranosyl)-2-amino-6-chlorop urine,

9-(3'-O-triflyl-2',5'-di-O-trityl-.beta.-D-ribofuranosyl)-2-amino-6-thiopur ine,

9-(3'-O-triflyl-2',5'-di-O-trityl-.beta.-D-ribofuranosyl)-2-amino-6-methylt hiopurine,

9-(3'-O-triflyl-2',5'-di-O-trityl-.beta.-D-ribofuranosyl)-2-fluoropurine,

9-(3'-O-triflyl-2',5'-di-O-trityl-.beta.-D-ribofuranosyl)-2-fluoro-6-thiopu rine,

9-(3'-O-triflyl-2',5'-di-O-trityl-.beta.-D-ribofuranosyl)-2-fluoro-6-methyl thiopurine,

9-(3'-O-triflyl-2',5'-di-O-trityl-.beta.-D-ribofuranosyl)-2-fluoro-6-aminom ethylpurine,

9-(3'-O-triflyl-2',5'-di-O-trityl-.beta.-D-ribofuranosyl)-2-fluoro-6-dimeth ylaminopurine,

9-(3'-O-triflyl-2',5'-di-O-trityl-.beta.-D-ribofuranosyl)-N.sup.6 -trityladenine,

9-(3'-O-triflyl-2',5'-di-O-trityl-.beta.-D-ribofuranosyl)-N.sup.6 -acetyladenine,

9-(3'-O-triflyl-2',5'-di-O-trityl-.beta.-D-ribofuranosyl)-N.sup.6 -benzoyladenine,

9-(3'-O-triflyl-2',5'-di-O-trityl-.beta.-D-ribofuranosyl)-2-fluoroadenine,

9-(5'-O-trityl-.beta.-D-ribofuranosyl)-1-benzylhypoxanthine,

9-(5'-O-trityl-.beta.-D-ribofuranosyl)-2-fluorohypoxanthine,

9-(3'-O-acetyl-2'-O-triflyl-5'-O-trityl-.beta.-D-ribofuranosyl)-1-benzylhyp oxanthine,

9-(3'-O-acetyl-2'-O-triflyl-5'-O-trityl-.beta.-D-ribofuranosyl)-2-acetamido guanine,

9-(3'-O-acetyl-2'-O-triflyl-5'-O-trityl-.beta.-D-ribofuranosyl)-2-benzamido guanine,

9-(3'-O-acetyl-2'-O-triflyl-5'-O-trityl-.beta.-D-ribofuranosyl)-2-isobutana midoguanine,

9-(3'-O-acetyl-2'-O-triflyl-5'-O-trityl-.beta.-D-ribofuranosyl)-2-acetamido -6-thioguanine,

9-(3'-O-acetyl-2'-O-triflyl-5'-O-trityl-.beta.-D-ribofuranosyl)-2-benzamido -6-thioguanine,

9-(3'-O-acetyl-2'-O-triflyl-5'-O-trityl-.beta.-D-ribofuranosyl)-2-isobutana mido-6-thioguanine,

9-(3'-O-acetyl-2'-O-triflyl-5'-O-trityl-.beta.-D-ribofuranosyl)-2-fluorohyp oxanthine,

9-(2',5'-di-O-trityl-.beta.-D-ribofuranosyl)-hypoxanthine,

9-(2',5'-di-O-trityl-.beta.-D-ribofuranosyl)-1-benzylhypoxanthine,

9-(2',5'-di-O-trityl-.beta.-D-ribofuranosyl)-N.sup.2 -tritylguanine,

9-(2',5'-di-O-trityl-.beta.-D-ribofuranosyl)-N.sup.2 -acetylguanine,

9-(2',5'-di-O-trityl-.beta.-D-ribofuranosyl)-N.sup.2 -benzoylguanine,

9-(2',5'-di-O-trityl-.beta.-D-ribofuranosyl)-N.sup.2 -isobutyrylguanine,

9-(2',5'-di-O-trityl-.beta.-D-ribofuranosyl)-2-fluorohypoxanthine,

9-(3',5'-di-O-trityl-.beta.-D-ribofuranosyl)-hypoxanthine,

9-(3',5'-di-O-trityl-.beta.-D-ribofuranosyl)-1-benzylhypoxanthine,

9-(3',5'-di-O-trityl-.beta.-D-ribofuranosyl)-N.sup.2 -isobutyrylguanine,

9-(3',5'-di-O-trityl-.beta.-D-ribofuranosyl)-2-fluorohypoxanthine,

9-(2'-O-trityl-3',5'-di-O-trityl-.beta.-D-ribofuranosyl)-hypoxanthine,

9-(2'-O-triflyl-3',5'-di-O-trityl-.beta.-D-ribofuranosyl)-1-benzylhypoxanth ine,

9-(2'-O-triflyl-3',5'-di-O-trityl-.beta.-D-ribofuranosyl)-2-fluorohypoxanth ine,

9-(2'-O-triflyl-3',5'-di-O-trityl-.beta.-D-ribofuranosyl)-6-thiohypoxanthin e,

9-(2'-O-triflyl-3',5'-di-O-trityl-.beta.-D-ribofuranosyl)-N6-tritylguanine,

9-(2'-O-triflyl-3',5'-di-O-trityl-.beta.-D-ribofuranosyl)-N.sup.2 -acetylguanine,

9-(2'-O-triflyl-3',5'-di-O-trityl-.beta.-D-ribofuranosyl)-N.sup.2 -benzoylguanine,

9-(2'-O-triflyl-3',5'-di-O-trityl-.beta.-D-ribofuranosyl)-N.sup.2 -isobutyrylguanine,

9-(2'-O-triflyl-3',5'-di-O-trityl-.beta.-D-ribofuranosyl)-6-thio-N.sup.2 -acetylguanine,

9-(2'-O-triflyl-3',5'-di-O-trityl-.beta.-D-ribofuranosyl)-6-thio-N.sup.2 -benzoylguanine,

9-(2'-O-triflyl-3',5'-di-O-trityl-.beta.-D-ribofuranosyl)-6-thio-N.sup.2 -isobutyrylguanine,

9-(2'-O-triflyl-3',5'-di-O-trityl-.beta.-D-ribofuranosyl)-2-fluorohypoxanth ine,

9-(3'-O-triflyl-2',5'-di-O-trityl-.beta.-D-ribofuranosyl)-hypoxanthine,

9-(3'-O-triflyl-2',5'-di-O-trityl-.beta.-D-ribofuranosyl)-1-benzyl-hypoxant hine,

9-(3'-O-triflyl-2',5'-di-O-trityl-.beta.-D-ribofuranosyl)-2-fluoro-hypoxant hine,

9-(3'-O-triflyl-2',5'-di-O-trityl-.beta.-D-ribofuranosyl)-6-thio-hypoxanthi ne,

9-(3'-O-triflyl-2',5'-di-O-trityl-.beta.-D-ribofuranosyl)-N.sup.2 -tritylguanine,

9-(3'-O-triflyl-2',5'-di-O-trityl-.beta.-D-ribofuranosyl)-N.sup.2 -acetylguanine,

9-(3'-O-triflyl-2',5'-di-O-trityl-.beta.-D-ribofuranosyl)-N.sup.2 -benzoylguanine,

9-(3'-O-triflyl-2',5'-di-O-trityl-.beta.-D-ribofuranosyl)-N.sup.2 -isobutyrylguanine,

9-(3'-O-triflyl-2',5'-di-O-trityl-.beta.-D-ribofuranosyl)-N.sup.2 -trityl-6-thioguanine,

9-(3'-O-triflyl-2',5'-di-O-trityl-.beta.-D-ribofuranosyl)-6-thio-N.sup.2 -acetylguanine,

9-(3'-O-triflyl-2',5'-di-O-trityl-.beta.-D-ribofuranosyl)-6-thio-N.sup.2 -benzoylguanine,

9-(3'-O-triflyl-2',5'-di-O-trityl-.beta.-D-ribofuranosyl)-6-thio-N.sup.2 -isobutyrlguanine, or

9-(3'-O-triflyl-2',5'-di-O-trityl-.beta.-D-ribofuranosyl)-2-fluorohypoxanth ine.

The present invention also provides a compound having the structure: ##STR23## wherein R.sup.5 is triphenylmethyl, diphenyl(4-methoxyphenyl)methyl, or phenyldi(4-methoxyphenyl)methyl;

R.sup.3 is hydrogen, triflyl, triphenylmethyl, diphenyl(4-methoxyphenyl)methyl, phenyldi(4-methoxyphenyl)methyl, tetrahydropyranyl, acetyl, propanoyl, benzoyl, anisoyl, toluoyl, nitrobenzoyl, benzyl, toluyl, methoxybenzyl, or nitrobenzyl;

R.sup.1 is hydrogen, benzyl or a substituted benzyl group;

X is hydrogen, a fluoro, an amino or a substituted amino;

Y is hydrogen, a methoxy, a methylthio, a benzylthio, an isopropyl, a chloro, an amino or a substituted amino;

Y' is an oxo or a thio group; and

Z is hydrogen, a hydroxy, a methoxy, a halogen, an amino or a substituted amino;

Compounds having the above-identified structure, although not limited to the following compounds, may be selected from the group consisting of:

9-(3'-O-acetyl-2'-deoxy-2'-fluoro-5'-O-trityl-.beta.-D-arabinofuranosyl) purine,

9-(3'-O-acetyl-2'-deoxy-2'-fluoro-5'-O-trityl-.beta.-D-arabinofuranosyl)-6- chloropurine,

9-(3'-O-acetyl-2'-deoxy-2'-fluoro-5'-O-trityl-.beta.-D-arabinofuranosyl)-6- thiopurine,

9-(3'-O-acetyl-2'-deoxy-2'-fluoro-5'-O-trityl-.beta.-D-arabinofuranosyl)-6- methylthiopurine,

9-(3'-O-acetyl-2'-deoxy-2'-fluoro-5'-O-trityl-.beta.-D-arabinofuranosyl)-6- aminomethylpurine,

9-(3'-O-acetyl-2'-deoxy-2'-fluoro-5'-O-trityl-.beta.-D-arabinofuranosyl)-6- dimethylpurine,

9-(3'-O-acetyl-2'-deoxy-2'-fluoro-5'-O-trityl-.beta.-D-arabinofuranosyl)-6- acetamidopurine,

9-(3'-O-acetyl-2'-deoxy-2'-fluoro-5'-O-trityl-.beta.-D-arabinofuranosyl)-2- benzamidopurine,

9-(3'-O-acetyl-2'-deoxy-2'-fluoro-5'-O-trityl-.beta.-D-arabinofuranosyl)-2- isobutanamidopurine,

9-(3'-O-acetyl-2'-deoxy-2'-fluoro-5'-O-trityl-.beta.-D-arabinofuranosyl)-N. sup.2 -isobutyryl-6-thiopurine,

9-(3'-O-acetyl-2'-deoxy-2'-fluoro-5'-O-trityl-.beta.-D-arabinofuranosyl)-2, 6-diacetamidopurine,

9-(3'-O-acetyl-2'-deoxy-2'-fluoro-5'-O-trityl-.beta.-D-arabinofuranosyl)-2, 6-diabenzamidopurine,

9-(3'-O-acetyl-2'-deoxy-2'-fluoro-5'-O-trityl-.beta.-D-arabinofuranosyl)-2, 6-diisobutanamidopurine,

9-(3'-O-acetyl-2'-deoxy-2'-fluoro-5'-O-trityl-.beta.-D-arabinofuranosyl)-2- acetamido-6-chloropurine,

9-(3'-O-acetyl-2'-deoxy-2'-fluoro-5'-O-trityl-.beta.-D-arabinofuranosyl)-2- acetamido-6-thiopurine,

9-(3'-O-acetyl-2'-deoxy-2'-fluoro-5'-O-trityl-.beta.-D-arabinofuranosyl)-2- acetamido-6-methylthiopurine,

9-(3'-O-acetyl-2'-deoxy-2'-fluoro-5'-O-trityl-.beta.-D-arabinofuranosyl)-2- fluoropurine,

9-(3'-O-acetyl-2'-deoxy-2'-fluoro-5'-O-trityl-.beta.-D-arabinofuranosyl)-2- fluoro-6-thiopurine,

9-(3'-O-acetyl-2'-deoxy-2'-fluoro-5'-O-trityl-.beta.-D-arabinofuranosyl)-2- fluoro-6-methylthiopurine,

9-(3'-O-acetyl-2'-deoxy-2'-fluoro-5'-O-trityl-.beta.-D-arabinofuranosyl)-2- fluoro-6-dimethylaminopurine.

9-(3'-O-acetyl-2'-deoxy-2'-fluoro-5'-O-trityl-.beta.-D-arabinofuranosyl)ade nine,

9-(3'-O-acetyl-2'-deoxy-2'-fluoro-5'-O-trityl-.beta.-D-arabinofuranosyl)-N. sup.6 -acetyladenine,

9-(3'-O-acetyl-2'-deoxy-2'-fluoro-5'-O-trityl-.beta.-D-arabinofuranosyl)-N. sup.6 -benzoyladenine,

9-(3'-O-acetyl-2'-deoxy-2'-fluoro-5'-O-trityl-.beta.-D-arabinofuranosyl)-N. sup.6 -trityladenine,

9-(3'-O-acetyl-2'-deoxy-2'-fluoro-5'-O-trityl-.beta.-D-arabinofuranosyl)-2- fluoroadenine,

9-(2'deoxy-2-fluoro-3',5'-di-O-trityl-.beta.-D-arabinofuranosyl)purine,

9-(2'deoxy-2-fluoro-3',5'-di-O-trityl-.beta.-D-arabinofuranosyl)-6-chloropu rine,

9-(2'deoxy-2-fluoro-3',5'-di-O-trityl-.beta.-D-arabinofuranosyl)-6-thiopuri ne,

9-(2'deoxy-2-fluoro-3',5'-di-O-trityl-.beta.-D-arabinofuranosyl)-6-methylth iopurine,

9-(2'deoxy-2-fluoro-3',5'-di-O-trityl-.beta.-D-arabinofuranosyl)-6-aminomet hylpurine,

9-(2'deoxy-2-fluoro-3',5'-di-O-trityl-.beta.-D-arabinofuranosyl)-6-dimethyl aminopurine,

9-(2'deoxy-2-fluoro-3',5'-di-O-trityl-.beta.-D-arabinofuranosyl)-2-aminopur ine,

9-(2'deoxy-2-fluoro-3',5'-di-O-trityl-.beta.-D-arabinofuranosyl)-2-benzamid opurine,

9-(2'deoxy-2-fluoro-3',5'-di-O-trityl-.beta.-D-arabinofuranosyl)-2-isobytan amidopurine,

9-(2'deoxy-2-fluoro-3',5'-di-O-trityl-.beta.-D-arabinofuranosyl)-2,6-diamin opurine,

9-(2'deoxy-2-fluoro-3',5'-di-O-trityl-.beta.-D-arabinofuranosyl)-2,6-diacet amidopurine,

2,3-Dihydro-3-(2-pyridinyl)-4H-1-benzopyran-4-one N-oxides	4-arylisoindole analgesics
Acrolein oxidation catalyst	Adaptable aiming support
Adhesive composition	Adhesive tape
Adjustable boat trailer step assembly	Adjustable sanding device
Alkoxycarbonylalkylphospholipids and alkylaminocarbonylalkylphospholipids	All optical needs
Angle measuring device	Animal eartag electronic transponder
Anti-fuel slosh circuit	Antiparasitic avermectin derivatives
Apparatus for decorating bowling balls	Arithmetic processor
Arrow vane	Article transferring apparatus
Artifical heart	Assay device
Auger for combine header	Austenitic stainless steel
Automatic correction for color printing	Automatic mixed drink dispensing apparatus
Automatic sewing machine	Automatic sound field correcting device
Automatically optimized combustion control	Bag with integral bottom case
Balloon catheter for photodynamic therapy	Band sawmill
Bending table	Beverage holder
Bidirectional check valve catheter	Binocular zoom microscope
Biopsy needle and surgical instrument	Blind liner for service pipes
Boot holster	Box construction
Bracketed stacking of multi-pin connectors	Braking assembly and system
Bright tin electrodeposition composition	Cable exit trough with insert
Cable reel	Camera system
Card information selecting system	Cardioprotective tocopherol analogs
Carriage moving device	Carrier for a framed canvas
Catalysts for polymerizing olefins	Catalysts of nickel and uranium
Catalytic converter	Centering clamping device
Chair bathtub	Chip mounting apparatus
Clamp calibration apparatus and method	Closed torus tire
Coaxial type starter	Combustion augmented plasma gun
Combustion monitoring	Compact navigation system and method
Complementary bipolar harmonic mixer	Connector blocks for telecommunications lines
Container closure	Control valve
Controllable vehicle strut	Corner shelf assembly
Corrugated paperboard pallet deck	Countersunk head screw
Cracking catalyst	Crib or youthbed
Curable siloxane maleimide composition	CVD diamond radiation detector
Data processing equipment and method	Data replication system and method
Data transport control apparatus	Data-reproducing device
Decorative hanging lighting apparatus	Delivery device for continuous threads
Device for detecting pericardial effusion	Device for storage of hydrogen
Dirty air filter indicator	Dishwasher
Dispensing device for medicaments	Distributed positive train control system
Dome funnel	Dough processing and conveyor system
Electric gas lighter	Electrical harness analyzer
Electrically heated tree stand	Electroacoustical transducer
Electromagnetic relay	Electronic verification machine for documents
Electronic-monetary system	Electronically programmable read only memory
Electrostatic printhead	Embroidery data editing device
Emergency fireman life-support device	Explosive plug for blocking tubes
Extendible gripper	Fatigue analysis and warning system
Feed through	Fiber-optic connector
Field/frame conversion circuit	Fingerprint detecting device and method
Fitting	Flame retardant polycarbonate composition
Flash camera	Flexible stent
Flood prevention valve	Fluid motor metering device
Fluorescent lamp light ballast system	Foot operated cutting device
Foot scrubbing and massaging device	Freight handling method
Frictionally held receptacle	Frozen foodstuffs thawing detector device
Fuel injection pumping apparatus	Fungicidally active compounds
Fusion of processor micro-operations	Gas supply and distribution center
Gene trap vectors	Getter assembly
Glue gun holder apparatus	Gumming machine
Gyratory cone crusher	Hair removal device and method
Handle for sleeve-type carrier	Handwheel disengage mechanism
Hawser chain seal assembly	Haylage/silage moisture tester
Head feed device	Heat sealing apparatus
High speed trimming shear	Hub for a bicycle
Human CCN-like growth factor	Hydraulic presses
Hydraulic vehicle brake system	Hydro-pneumatic braking device
Hydrocarbon dehydrogenation process	Hydrosoluble acrylic copolymers
Illuminating apparatus	Image processing system
Image resolution	Implantable medical power module
Inductive displacement sensor apparatus	Information reproducing system and method
Ink container refurbishment system	Ink jet printing process
Insert molded catheter tip	Inspection apparatus
Integrated reticle and detector	Interactive weather advisory system
Interlocking chemical mechanical polishing system	Ion exchange membrane for electrolysis
Ionographic image forming apparatus	Lamellar separator
Laser connector conversion adaptor	Lens apparatus
Lens mount	Lift for the handicapped
Light responsive monitoring system	Light-emitting diode arrangement
Liner with a composite upper	Liquid level sensor
Long wafer waferboard panels	Low stress die attachment
Magnetic head driving unit	Magnetically controlled obturator
Mammalian CDP-diacylglycerol synthase	Manually operated screen reeling device
Measurement of relative velocities	Meat chopper blade head
Mechanical oil can seal breaker	Memory for video signals
Memory present apparatus	Merchandise checkout work station
Method for inhibiting restenosis	Method of shaping fiber materials
Micro-strand cable with enhanced radiopacity	Microlens and long period gratings
Mine roof support	Mineral reinforced polyamides
Modified missile launcher	Modular humeral head resurfacing system
Multi-ply web former	Muntin joint
Nicotine removal process	Non-steroidal anabolic composition
Novel phosphorescent condoms	Optical calculating apparatus
Optical communication module	Optical information recording medium
Optical lens device assembly	Optical recording/reproducing apparatus
Orbital motion bearing	Pay phone
PCI riser card support	Percutaneous drug delivery system
Photochromic multifocal lenses	Photosensitive plate
Pipe pulling grip	Pneumatic control valve
Polygonal paperboard drum	Polymeric reaction products
Polymerization catalyst, production and use	Popped corn receptacle
Portable beverage dispenser	Prayer scroll
Preparation of arylphosphines	Pressure fluid actuator
Printer sharing device	Process for making bread
Process for preparing gum base	Projection exposure apparatus
Projection type display apparatus	Protective cushion
Punch unit	Radio communication system
Radiotelephone credit card data communications	Razor magnifying glass
Refilling ink jet cartridges	Reminder apparatus
Remote control mechanisms	Resin composition containing copolyphenylene ether
Reusable configuration tool	Robot crash protector
Roof ridge assemblies	Rotors for gas turbine engines
Scanning probe microscope	Screen and flow regulator assembly
Screening apparatus	Screening device
Sealing member for a container	Sealing ring having torsion ribs
Seat assembly of bicycle	Self cleaning chill roll apparatus
Self contained mechanical injector	Self-cooling water container
Self-locking devices	Self-retaining adsorbent unit
Semi-fixed type variable resistor	Semiconductor device
Semiconductor wafer transfer device	Sensing circuit with charge recycling
Separation of gases containing SF6	Shape adaptive process apparatus
Silver halide color photosensitive material	Simple pressure seal methods
Simplified fiber optic receptacle	Solar collector
Sound attenuator for pneumatic motors	Spear-blade swim fin
Spinal implant connection assembly	Splint for extremities
Stacked magnet superconducting bearing	Stratification resistant emulsions
Structure of clip container	Substituted caprolactam derivatives as antihypertensives
Substituted ureas as herbicides	Sugar cane planter
Supported catalyst	Surface mount circuit assembly
Synchronism check relay	Synthesis of N-acyl-N-alkylcarboxylates
Table attachment for arm chairs	Telecommunications management and control apparatus
Tennis training device	Test for fecal occult blood
Thermionic detector	Thermostable esterase and its gene
Thin film optical transmission device	Three-part seal construction
Thrombin inhibitor	Timer and alarm apparatus
Tobacco harverter	Toilet tank water conservation device
Toy racing game	Transaxle for a vehicle driveline
Transcutaneous galvanic electrode oxygen sensor	Transverse leaf spring type suspension
Treatment of inflammation	Treatment of traveller's diarrhea
Trench power MOSFET device	Twelve-sided polygon-shaped air bag
Underwater acoustic impedance measuring apparatus	Unsaturated polyester resin composition
Variable weight play ball	Vertical combustion furnace
Video display control apparatus	Video signal decoding circuit
VITERBI decoder	Wall hangable window simulating unit
Water-based paint useful for windshields	Wax-impregnated fire kindling sticks
Wheeled vehicle	Wire connector
Workpiece attaching and detaching apparatus	Wound dressing securement system
Zoom lens system

9-(2'deoxy-2-fluoro-3',5'-di-O-trityl-.beta.-D-arabinofuranosyl)-2,6-dibenz amidopurine,

9-(2'deoxy-2-fluoro-3',5'-di-O-trityl-.beta.-D-arabinofuranosyl)-2,6-diisob utanamidopurine,

9-(2'deoxy-2-fluoro-3',5'-di-O-trityl-.beta.-D-arabinofuranosyl)-2-amino-6- chloropurine,

9-(2'deoxy-2-fluoro-3',5'-di-O-trityl-.beta.-D-arabinofuranosyl)-2-amino-6- thiopurine,

9-(2'deoxy-2-fluoro-3',5'-di-O-trityl-.beta.-D-arabinofuranosyl)-2-amino-6- methylthiopurine,

9-(2'deoxy-2-fluoro-3',5'-di-O-trityl-.beta.-D-arabinofuranosyl)-2-fluoropu rine,

9-(2'deoxy-2-fluoro-3',5'-di-O-trityl-.beta.-D-arabinofuranosyl)-2-fluoro-6 -thiopurine,

9-(2'deoxy-2-fluoro-3',5'-di-O-trityl-.beta.-D-arabinofuranosyl)-2-fluoro-6 -methylthiopurine,

9-(2'deoxy-2-fluoro-3',5'-di-O-trityl-.beta.-D-arabinofuranosyl)-2-fluoro-6 -aminomethylpurine,

9-(2'deoxy-2-fluoro-3',5'-di-O-trityl-.beta.-D-arabinofuranosyl)-2-fluoro-6 -dimethylaminopurine,

9-(2'deoxy-2-fluoro-3',5'-di-O-trityl-.beta.-D-arabinofuranosyl)-2-fluoroad enine,

9-(2'deoxy-2-fluoro-3',5'-di-O-trityl-.beta.-D-arabinofuranosyl)-N.sup.6 -trityladenine,

9-(2'deoxy-2-fluoro-3',5'-di-O-trityl-.beta.-D-arabinofuranosyl)-N.sup.6 -acetyladenine,

9-(2'deoxy-2-fluoro-3',5'-di-O-trityl-.beta.-D-arabinofuranosyl)-N.sup.6 -benzoyladenine,

9-(2'deoxy-2-fluoro-3',5'-di-O-trityl-.beta.-D-arabinofuranosyl)-2-fluoroad enine,

9-(3'-O-acetyl-2'-deoxy-2'-fluoro-5'-O-trityl-.beta.-D-arabinofuranosyl)-N. sup.2 -acetylguanine,

9-(3'-O-acetyl-2'-deoxy-2'-fluoro-5'-O-trityl-.beta.-D-arabinofuranosyl)-N. sup.2 -benzoylguanine,

9-(3'-O-acetyl-2'-deoxy-2'-fluoro-5'-O-trityl-.beta.-D-arabinofuranosyl)-N. sup.2 -isobutyrylguanine,

9-(3'-O-acetyl-2'-deoxy-2'-fluoro-5'-O-trityl-.beta.-D-arabinofuranosyl)-N. sup.2 -acetyl-6-thioguanine,

9-(3'-O-acetyl-2'-deoxy-2'-fluoro-5'-O-trityl-.beta.-D-arabinofuranosyl)-N. sup.2 -benzoyl-6-thioguanine,

9-(3'-O-acetyl-2'-deoxy-2'-fluoro-5'-O-trityl-.beta.-D-arabinofuranosyl)-N. sup.2 -isobutyryl-6-thioguanine,

9-(3'-O-acetyl-2'-deoxy-2-fluoro-3',5'-di-O-trityl-.beta.-D-arabinofuranosy l)-thioguanine,

9-(2'deoxy-2-fluoro-3',5'-di-O-trityl-.beta.-D-arabinofuranosyl)-2-fluorohy poxanthine,

9-(2'deoxy-2-fluoro-3',5'-di-O-trityl-.beta.-D-arabinofuranosyl)-hypoxanthi ne,

9-(2'deoxy-2-fluoro-3',5'-di-O-trityl-.beta.-D-arabinofuranosyl)-guanine,

9-(2'deoxy-2-fluoro-3',5'-di-O-trityl-.beta.-D-arabinofuranosyl)-N.sup.2 -acetylguanine,

9-(2'deoxy-2-fluoro-3',5'-di-O-trityl-.beta.-D-arabinofuranosyl)-N.sup.2 -benzoylguanine,

9-(2'deoxy-2-fluoro-3',5'-di-O-trityl-.beta.-D-arabinofuranosyl)-N.sup.2 -isobutrylguanine, or

9-(2'deoxy-2-fluoro-3',5'-di-O-trityl-.beta.-D-arabinofuranosyl)-2-fluorohy poxanthine.

The following Experimental Detail Section and Examples are set forth to aid in an understanding of the invention. These sections are not intended to, and should not be construed to, limit in any way the invention set forth in the claims which follow thereafter.

EXPERIMENTAL DETAILS

Example 1

A mixture of 1-benzylinosine (3.58 g, 10 mmol) and trityl chloride (3.3 g, 12 mmol) in pyridine (50 mL is stirred overnight at room temperature. An additional amount of trityl chloride (3.3 g) is charged on the second and third days. The reaction is monitored by thin layer chromatography on silica gel plates using a mixture of chloroform and ethanol (10:1 v/v) as the developing solvent. After all the starting material is consumed, the mixture is concentrated in vacuo, and the residue coevaporated several times with toluene and ethanol, and then chromatographed on a silica column using chloroform-ethanol (19:1 v/v) as the eluent to give 5'-O-trityl-1-benzylinosine which is crystallized from ethanol: 5.40 g (90% yield), mp 208.degree.-209.degree. C. .sup.1 H NMR (Me.sub.2 SO-d.sub.6) .delta. 3.20-3.24 (2H, m, H-5',5"), 4.10-4.29 (2H, m, H-3',4'), 4.61-4.67 (1H, m, H-2', collapsed to dd upon addition of D.sub.2 O, J.sub.1',2' =5.6, J.sub.2',3' =5.0 Hz), 5.24 (2H, s, CH.sub.2 Ph), 5.21-5.27 (1H, m, OH, exchangeable), 5.57 (1H, d, OH), 5.92 (1H, d, H-1'), 7.06-7.32 (2OH, m, Tr, CH.sub.2 Ph), 8.23, 8.51 (1H each, H-2, H-8). Analyses: calculated for C.sub.26 H.sub.32 N.sub.4 O.sub.5 : C, 71.98, H, 5.37, N, 9.33. Found: C, 71.86, H, 5.44, N, 9.18.

By following the same procedure but using the corresponding nucleosides, the following 5'-O-trityl nucleosides are prepared:

9-(5'-O-trityl-.beta.-D-ribofuranosyl)purine,

9-(5'-O-trityl-.beta.-D-ribofuranosyl)-6-chloropurine,

9-(5'-O-trityl-.beta.-D-ribofuranosyl)-6-aminomethylpurine,

9-(5'-O-trityl-.beta.-D-ribofuranosyl)-2-aminopurine,

9-(5'-O-trityl-.beta.-D-ribofuranosyl)-2-acetamidopurine,

9-(5'-O-trityl-.beta.-D-ribofuranosyl)-2-benzamidopurine,

9-(5'-O-trityl-.beta.-D-ribofuranosyl)-2-isobutanamidopurine,

9-(5'-O-trityl-.beta.-D-ribofuranosyl)-2,6-diaminopurine,

9-(5'-O-trityl-.beta.-D-ribofuranosyl)-2,6-diacetamidopurine,

9-(5'-O-trityl-.beta.-D-ribofuranosyl)-2,6-dibenzamidopurine,

9-(5'-O-trityl-.beta.-D-ribofuranosyl)-2,6-diisobutanamidopurine,

9-(5'-O-trityl-.beta.-D-ribofuranosyl)-2-amino-6-chloropurine,

9-(5'-O-trityl-.beta.-D-ribofuranosyl)-2-amino-6-thiopurine,

9-(5'-O-trityl-.beta.-D-ribofuranosyl)-2-amino-6-methylthiopurine,

9-(5'-O-trityl-.beta.-D-ribofuranosyl)-2-fluropurine,

9-(5'-O-trityl-.beta.-D-ribofuranosyl)-2-fluoroadenine,

9-(5'-O-trityl-.beta.-D-ribofuranosyl)-2-fluorohypoxanthine,

9-(5'-O-trityl-.beta.-D-ribofuranosyl)-2-fluoro-6-thiopurine,

9-(5'-O-trityl-.beta.-D-ribofuranosyl)-2-fluoro-6-methylthiopurine,

9-(5'-O-trityl-.beta.-D-ribofuranosyl)-2-fluoro-6-aminomethylpurine, and

9-(5'-O-trityl-.beta.-D-ribofuranosyl)-2-fluoro-6-dimethylaminopurine.

Example 2

A mixture of 5'-O-trityladenosine (497 mg, 1 mmol) and dibutyltin oxide (249 mg, 1 mmol) in methanol (50 mL) is heated under reflux until a clear solution is obtained. The solution is concentrated in vacuo, the residue dissolved in dimethylformamide (20 mL). To the ice cooled solution is added triflyl chloride (190 mg, 1.1 mmol), and the mixture stirred for 90 minutes at room temperature, and then concentrated in vacuo. The residue is dissolved in pyridine (20 mL), and the solution treated with acetic anhydride (1.5 mL). After being stirred for 3 hours at room temperature, the mixture is concentrated in vacuo. The residue is chromatographed on a silica gel using a mixture of chloroform and ethanol (33:1 v/v) as the eluent to give 3'-O-acetyl-2'-O-triflyl-5'-O-trityladenosine (208 ) mg, 31% ) as a foam. .sup.1 H NMR (Me.sub.2 SO-d.sub.6) .delta. 2.12 (3H, s, OAc), 3.36-3.49 (2H, m, H-5'5"), 4.36-4.40 (1H, m, H-4'), 5.90-5.95 (1h, m, H-3'), 6.45-6.54 (2H, m, H-1',2'), 7.20-7.57 (17H, m, Tr, NH.sub.2), 8.06, 8.35 (1H each, s, H-2, H-8). Analyses: Calculated for C.sub.32 H.sub.28 F.sub.3 N.sub.5 O.sub.7 S: C, 71.94, H, 5.45, N, 10.24. Found: C, 71.67, H, 5.50, N, 10.27.

By following the same procedure but using the corresponding 5'-O-tritylnucleosides, the following 3'-O-acetyl-2'-O-triflyl-5'-O-tritylnucleosides are prepared:

9-(3'-O-acetyl-2'-O-triflyl-5'-O-trityl-.beta.-D-ribofuranosyl)purine,

9-(3'-O-acetyl-2'-O-triflyl-5'-O-trityl-.beta.-D-ribofuranosyl)-6-chloropur ine,

9-(3'-O-acetyl-2'-O-triflyl-5'-O-trityl-.beta.-D-ribofuranosyl)-6-thiopurin e,

9-(3'-O-acetyl-2'-O-triflyl-5'-O-trityl-.beta.-D-ribofuranosyl)-6-methylthi opurine,

9-(3'-O-acetyl-2'-O-triflyl-5'-O-trityl-.beta.-D-ribofuranosyl)-6-aminometh ylpurine,

9-(3'-O-acetyl-2'-O-triflyl-5'-O-trityl-.beta.-D-ribofuranosyl)-6-dimethyla minopurine,

9-(3'-O-acetyl-2'-O-triflyl-5'-O-trityl-.beta.-D-ribofuranosyl)-2-aminopuri ne,

9-(3'-O-acetyl-2'-O-triflyl-5'-O-trityl-.beta.-D-ribofuranosyl)-2-acetamido purine,

9-(3'-O-acetyl-2'-O-triflyl-5'-O-trityl-.beta.-D-ribofuranosyl)-2-benzamido purine,

9-(3'-O-acetyl-2'-O-triflyl-5'-O-trityl-.beta.-D-ribofuranosyl)-2-isobutana midopurine,

9-(3'-O-acetyl-2'-O-triflyl-5'-O-trityl-.beta.-D-ribofuranosyl)-2,6-diamino purine,

9-(3'-O-acetyl-2'-O-triflyl-5'-O-trityl-.beta.-D-ribofuranosyl)-2,6-diaceta midopurine,

9-(3'-O-acetyl-2'-O-triflyl-5'-O-trityl-.beta.-D-ribofuranosyl)-2,6-dibenza midopurine,

9-(3'-O-acetyl-2'-O-triflyl-5'-O-trityl-.beta.-D-ribofuranosyl)-2,6-diisobu tanamidopurine,

9-(3'-O-acetyl-2'-O-triflyl-5'-O-trityl-.beta.-D-ribofuranosyl)-2-amino-6-c hloropurine,

9-(3'-O-acetyl-2'-O-triflyl-5'-O-trityl-.beta.-D-ribofuranosyl)-2-amino-6-t hiopurine,

9-(3'-O-acetyl-2'-O-triflyl-5'-O-trityl-.beta.-D-ribofuranosyl)-2-amino-6-m ethylthiopurine,

9-(3'-O-acetyl-2'-O-triflyl-5'-O-trityl-.beta.-D-ribofuranosyl)-2-fluoropur ine,

9-(3'-O-acetyl-2'-O-triflyl-5'-O-trityl-.beta.-D-ribofuranosyl)-2-fluoro-6- thiopurine,

9-(3'-O-acetyl-2'-O-triflyl-5'-O-trityl-.beta.-D-ribofuranosyl)-2-fluoro-6- methylthiopurine,

9-(3'-O-acetyl-2'-O-triflyl-5'-O-trityl-.beta.-D-ribofuranosyl)-2-fluoro-6- aminomethylpurine,

9-(3'-O-acetyl-2'-O-triflyl-5'-O-trityl-.beta.-D-ribofuranosyl)-2-fluoro-6- dimethylaminopurine,

9-(3'-O-acetyl-2'-O-triflyl-5'-O-trityl-.beta.-D-ribofuranosyl)-N.sup.6 -acetyladenine,

9-(3'-O-acetyl-2'-O-triflyl-5'-O-trityl-.beta.-D-ribofuranosyl)-N.sup.6 -benzoyladenine,

9-(3'-O-acetyl-2'-O-triflyl-5'-O-trityl-.beta.-D-ribofuranosyl)-N.sup.6 -trityladenine,

9-(3'-O-acetyl-2'-O-triflyl-5'-O-trityl-.beta.-D-ribofuranosyl)-2-fluoroade nine,

9-(3'-O-acetyl-2'-O-triflyl-5'-O-trityl-.beta.-D-ribofuranosyl)-1-benzylhyp oxanthine,

9-(3'-O-acetyl-2'-O-triflyl-5'-O-trityl-.beta.-D-ribofuranosyl)-2-acetamido guanine,

9-(3'-O-acetyl-2'-O-triflyl-5'-O-trityl-.beta.-D-ribofuranosyl)-2-benzamido guanine,

9-(3'-O-acetyl-2'-O-triflyl-5'-O-trityl-.beta.-D-ribofuranosyl)-2-isobutana midoguanine,

9-(3'-O-acetyl-2'-O-triflyl-5'-O-trityl-.beta.-D-ribofuranosyl)-2-acetamido -6-thioguanine,

9-(3'-O-acetyl-2'-O-triflyl-5'-O-trityl-.beta.-D-ribofuranosyl)-2-benzamido -6-thioguanine,

9-(3'-O-acetyl-2'-O-triflyl-5'-O-trityl-.beta.-D-ribofuranosyl)-2-isobutana mido-6-thioguanine, and

9-(3'-O-acetyl-2'-O-triflyl-5'-O-trityl-.beta.-D-ribofuranosyl)-2-fluorohyp oxanthine.

Example 3

To a stirred solution of 3'-O-acetyl-2'-O-triflyl-5'-O-trityladenosine (1.0 g, 1.46 mmol) in dry methylene chloride (10 mL) is added a solution of TASF (1.2 g, 1.46 mmol) in methylene chloride (9 mL) in an argon atmosphere at -70.degree. C. The mixture is allowed to warm to room temperature and the stirring is continued. After 24 hours of stirring, an additional amount of TASF (1.2 g) is charged, and the stirring is continued for another 24 hours. The reaction is quenched by addition of water (15 mL). The organic layer is separated, washed with water (5 mL), dried over sodium sulfate, and then concentrated in vacuo. The residue is placed on the top of a silica gel column, which is washed successively with chloroform containing 1% of ethanol, 3% of ethanol and then 5% ethanol. 4-Acetoxy-6-O-tritylfurfurol (220 mg, 37% yield, mp 79.degree.-83.degree. C. from n-hexane-ethylether) eluted first followed by 4-hydroxy-6-O-tritylfurfurol (80 mg, 15% yield, mp 119.degree.-120.degree. C. from n-hexane-ethylether), 9-(3'-O-acetyl-2'-deoxy-2'fluoro-5'-O-trityl-.beta.-D-arabinofuranosyl)ade nine (33 mg, 4% yield), a foam, .sup.1 H NMR (Me.sub.2 SO-d.sub.6) .delta. 2.10 (3H, s, OAc), 3.38-3.40 (2H, m, H-5',5"), 4.20-4.24 (1H, m, H-4'), 5.57 (1H, dm, H-3', J.sub.3',F =16.1 Hz), 5.52 (1H, dm, H-2', J.sub.2',F =51.6 Hz), 6.49 (1H, dd, J.sub.1,2' =3.8, J.sub.1',F =17.0 Hz), 7.25-7.36 (15H, m, Tr), 8.07 (1H, d, H-8, J.sub.8,F =2.5 Hz) 8.15 (1H, s, H-2), Analyses calculated for C.sub.31 H.sub.28 F.sub.3 N.sub.5 O.sub.4 : C, 67.26, H, 5.10, N, 12.65. Found: C, 67.30, H, 5.21, N, 12.50, and 9-(2',3'-di-O-acetyl-5'-O-trityl-.beta.-D-arabinofuranosyl)-adenine (104 mg, 12% yield).

By following the same procedure but using the corresponding 3'-O-acetyl-2'-O-triflyl-5'-O-tritylnucleosides, the following 9-(3'-O-acetyl-2'-deoxy-2'-fluoro-5'-O-triyl-.beta.-D-arabinofuranosyl)-nu cleosides are prepared in 4 to 10% yield:

9-(3'-O-acetyl-2'-deoxy-2'-fluoro-5'-O-trityl-.beta.-D-arabinofuranosyl)pur ine,

9-(3'-O-acetyl-2'-deoxy-2'-fluoro-5'-O-trityl-.beta.-D-arabinofuranosyl)-6- chloropurine,

9-(3'-O-acetyl-2'-deoxy-2'-fluoro-5'-O-trityl-.beta.-D-arabinofuranosyl)-6- thiopurine,

9-(3'-O-acetyl-2'-deoxy-2'-fluoro-5'-O-trityl-.beta.-D-arabinofuranosyl)-6- methylthiopurine,

9-(3'-O-acetyl-2'-deoxy-2'-fluoro-5'-O-trityl-.beta.-D-arabinofuranosyl)-6- aminomethylpurine,

9-(3'-O-acetyl-2'-deoxy-2'-fluoro-5'-O-trityl-.beta.-D-arabinofuranosyl)-6- dimethylpurine,

9-(3'-O-acetyl-2'-deoxy-2'-fluoro-5'-O-trityl-.beta.-D-arabinofuranosyl)-2- acetamidopurine,

9-(3'-O-acetyl-2'-deoxy-2'-fluoro-5'-O-trityl-.beta.-D-arabinofuranosyl)-2- benzamidopurine,

9-(3'-O-acetyl-2'-deoxy-2'-fluoro-5'-O-trityl-.beta.-D-arabinofuranosyl)-2- isobutanamidopurine,

9-(3'-O-acetyl-2'-deoxy-2'-fluoro-5'-O-trityl-.beta.-D-arabinofuranosyl)-2, 6-diacetamidopurine,

9-(3'-O-acetyl-2'-deoxy-2'-fluoro-5'-O-trityl-.beta.-D-arabinofuranosyl)-2, 6-dibenzamidopurine,

9-(3'-O-acetyl-2'-deoxy-2'-fluoro-5'-O-trityl-.beta.-D-arabinofuranosyl)-2, 6-diisobutanamidopurine,

9-(3'-O-acetyl-2'-deoxy-2'-fluoro-5'-O-trityl-.beta.-D-arabinofuranosyl)-2- acetamido-6-chloropurine,

9-(3'-O-acetyl-2'-deoxy-2'-fluoro-5'-O-trityl-.beta.-D-arabinofuranosyl)- 2-acetamido-6-thiopurine,

9-(3'-O-acetyl-2'-deoxy-2'-fluoro-5'-O-trityl-.beta.-D-arabinofuranosyl)-2- acetamido-6-methylthiopurine,

9-(3'-O-acetyl-2'-deoxy-2'-fluoro-5'-O-trityl-.beta.-D-arabinofuranosyl)-2- fluoropurine,

9-(3'-O-acetyl-2'-deoxy-2'-fluoro-5'-O-trityl-.beta.-D-arabinofuranosyl)-2- fluoro-6-thiopurine,

9-(3'-O-acetyl-2'-deoxy-2'-fluoro-5'-O-trityl-.beta.-D-arabinofuranosyl)-2- fluoro-6-methylthiopurine,

9-(3'-O-acetyl-2'-deoxy-2'-fluoro-5'-O-trityl-.beta.-D-arabinofuranosyl)-2- fluoro-6-aminomethylpurine,

9-(3'-O-acetyl-2'-deoxy-2'-fluoro-5'-O-trityl-.beta.-D-arabinofuranosyl)-2- fluoro-6-dimethylaminopurine,

9-(3'-O-acetyl-2'-deoxy-2'-fluoro-5'-O-trityl-.beta.-D-arabinofuranosyl)-N. sup.6 -acetyladenine,

9-(3'-O-acetyl-2'-deoxy-2'-fluoro-5'-O-trityl-.beta.-D-arabinofuranosyl)-N. sup.6 -benzoyladenine,

9-(3'-O-acetyl-2'-deoxy-2'-fluoro-5'-O-trityl-.beta.-D-arabinofuranosyl)-N. sup.6 -trityladenine,

9-(3'-O-acetyl-2'-deoxy-2'-fluoro-5'-O-trityl-.beta.-D-arabinofuranosyl)-2- fluoroadenine,

9-(3'-O-acetyl-2'-deoxy-2'-fluoro-5'-O-trityl-.beta.-D-arabinofuranosyl)-N. sup.2 -acetylguanine,

9-(3'-O-acetyl-2'-deoxy-2'-fluoro-5'-O-trityl-.beta.-D-arabinofuranosyl)-N. sup.2 -benzoylguanine,

9-(3'-O-acetyl-2'-deoxy-2'-fluoro-5'-O-trityl-.beta.-D-arabinofuranosyl)-N. sup.2 -isobutyrylguanine,

9-(3'-O-acetyl-2'-deoxy-2'-fluoro-5'-O-trityl-.beta.-D-arabinofuranosyl)-N. sup.2 -acetyl-6-thioguanine,

9-(3'-O-acetyl-2'-deoxy-2'-fluoro-5'-O-trityl-.beta.-D-arabinofuranosyl)-N. sup.2 -benzoyl-6-thioguanine, and

9-(3'-O-acetyl-2'-deoxy-2'-fluoro-5'-O-trityl-.beta.-D-arabinofuranosyl)-N. sup.2 -isobutyryl-6-thioguanine.

Example 4

A mixture of 1-benzylinosine (50.0 g, 0.14 mol), 4-dimethylaminopyridine (25.3 g, 0.21 mol) and trityl chloride (97.2 g, 0.35 mol) in pyridine (550 mL) is heated at 70.degree.-80.degree. C. for 3 days. An additional amount of trityl chloride (58.3 g) and dimethylamino-pyridine (10 g) is charged after 24 hours of reaction, and another charge of trityl chloride (39 g) and dimethylaminopyridine (6.0 g) after 48 hours. The reaction mixture is filtered while hot, the filtrate is concentrated in vacuo, and the residue coevaporated with toluene (2.times.300 mL). The residue is chromatographed on a silica gel column (40.times.10 cm) using n-hexane-ethyl acetate (1:1 v/v) as the eluent followed by n-hexane-ethyl acetate (1:1 v/v) containing increasing amount of ethanol from 3% to 30%.

Fractions containing di-O-tritylnucleosides are combined, concentrated in vacuo, and the residue rechromatographed on a silica gel column using n-hexane-chloroform-ethanol (20:20:1 v/v/v) followed by n-hexane-chloroform-ethanol (10:20:1 v/v/v) as the eluents.

2',5'-di-O-trityl-1-benzlinosine, which is eluted first from the column, is obtained as colorless crystals after recrystalization from n-hexane-ethyl acetate (28.0 g, 24% yield), mp 231.degree.-233.degree.C., .sup.1 H NMR (Me.sub.2 SO-d.sub.6) .delta. 3.00-3.06 (2H, m, H-5',5"), 3.20-3.24 (1H, m, H-4'), 4.05-4.09 (1H, m, H-3'), 4.95-5.02 (1H, m, H-2'), 5.15-5.22 (1H, m, OH), 5.22 (2H, m, CH.sub.2 Ph), 5.96 (1H, d, H-1', J.sub.1'2' =6.2 Hz), 7.02-7.64 (35H, 2 x Tr and CH.sub.2 Ph), 8.08, 8.17 (1H each, s, H-2, H-8). Analyses calculated for C.sub.55 H.sub.46 N.sub.4 O.sub.5 : C, 78.36, H, 5.50, N, 6.65. Found: C, 78.17, H, 5.36, N, 6.40.

3',5'-di-O-trityl-1-benzylinosine, which is eluted from the column next, is also obtained as colorless crystals (22.0 g, 9% yield), mp 187.degree.-188.degree.C., .sup.1 H NMR (Me.sub.2 SO-d.sub.6) .delta. 2.64-2.68 (2H, m, H-5'5"), 3.09-3.11 (1H, m, H-4'), 4.12-4.14 (1H, m, H-3'), 4.70-4.77 (1H, m, H-2'), 5.25 (2H, s, CH.sub.2 Ph), 6.10 (1H, d, H-1', J.sub.1'2' =7.2 Hz), 7.19-7.40 (35H, m, 2 x Tr and CH.sub.2 Ph), 8.15, 8.42 (1H each, s, H-2, H-8). Analyses calculated for C.sub.55 H.sub.46 N.sub.4 O.sub.5 : C, 78.36, H, 5.50, N, 6.65. Found: C, 78.20, H, 5.41, N, 6.52.

By following the same procedure but using the corresponding nucleosides, the following 2',5'-di-O-trityl and 3',5'-di-O-trityl nucleosides may be prepared in 15 to 33% yield:

9-(2',5'-di-O-trityl-.beta.-D-ribofuranosyl)-hypoxanthine,

9-(2',5'-di-O-trityl-.beta.-D-ribofuranosyl)-N.sup.6 -trityladenine,

9-(2',5'-di-O-trityl-.beta.-D-ribofuranosyl)-N.sup.6 -acetyladenine,

9-(2',5'-di-O-trityl-.beta.-D-ribofuranosyl)-N.sup.6 -benzoyladenine,

9-(2',5'-di-O-trityl-.beta.-D-ribofuranosyl)-N.sup.2 -tritylguanine,

9-(2',5'-di-O-trityl-.beta.-D-ribofuranosyl)-N.sup.2 -acetylguanine,

9-(2',5'-di-O-trityl-.beta.-D-ribofuranosyl)-N.sup.2 -benzoylguanine,

9-(2',5'-di-O-trityl-.beta.-D-ribofuranosyl)-N.sup.2 -isobutyrylguanine,

9-(2',5'-di-O-trityl-.beta.-D-ribofuranosyl)purine,

9-(2',5'-di-O-trityl-.beta.-D-ribofuranosyl)-6-chloropurine,

9-(2',5'-di-O-trityl-.beta.-D-ribofuranosyl)-6-thiopurine,

9-(2',5'-di-O-trityl-.beta.-D-ribofuranosyl)-6-methylthiopurine,

9-(2',5'-di-O-trityl-.beta.-D-ribofuranosyl)-6-aminomethylpurine,

9-(2',5'-di-O-trityl-.beta.-D-ribofuranosyl)-6-dimethylaminopurine,

9-(2',5'-di-O-trityl-.beta.-D-ribofuranosyl)-2-aminopurine,

9-(2',5'-di-O-trityl-.beta.-D-ribofuranosyl)-2-acetamidopurine,

9-(2',5'-di-O-trityl-.beta.-D-ribofuranosyl)-2-benzamidopurine,

9-(2',5'-di-O-trityl-.beta.-D-ribofuranosyl)-2-isobutanamidopurine,

9-(2',5'-di-O-trityl-.beta.-D-ribofuranosyl)-2,6-diaminopurine,

9-(2',5'-di-O-trityl-.beta.-D-ribofuranosyl)-2,6-diacetamidopurine,

9-(2',5'-di-O-trityl-.beta.-D-ribofuranosyl)-2,6-dibenzamidopurine,

9-(2',5'-di-O-trityl-.beta.-D-ribofuranosyl)-2,6-diisobutanamidopurine,

9-(2',5'-di-O-trityl-.beta.-D-ribofuranosyl)-2-amino-6-chloropurine,

9-(2',5'-di-O-trityl-.beta.-D-ribofuranosyl)-2-amino-6-thiopurine,

9-(2',5'-di-O-trityl-.beta.-D-ribofuranosyl)-2-amino-6-methylthiopurine,

9-(2',5'-di-O-trityl-.beta.-D-ribofuranosyl)-2-fluoropurine,

9-(2',5'-di-O-trityl-.beta.-D-ribofuranosyl)-2-fluoroadenine,

9-(2',5'-di-O-trityl-.beta.-D-ribofuranosyl)-2-fluorohypoxanthine,

9-(2',5'-di-O-trityl-.beta.-D-ribofuranosyl)-2-fluoro-6-thiopurine,

9-(2',5'-di-O-trityl-.beta.-D-ribofuranosyl)-2-fluoro-6-methylthiopurine,

9-(2',5'-di-O-trityl-.beta.-D-ribofuranosyl)-2-fluoro-6-aminomethylpurine,

9-(2',5'-di-O-trityl-.beta.-D-ribofuranosyl)-2-fluoro-6-dimethylaminopurine .

9-(3',5'-di-O-trityl-.beta.-D-ribofuranosyl)-hypoxanthine,

9-(3',5'-di-O-trityl-.beta.-D-ribofuranosyl)-N.sup.6 -trityladenine,

9-(3',5'-di-O-trityl-.beta.-D-ribofuranosyl)-N.sup.6 -acetyladenine,

9-(3',5'-di-O-trityl-.beta.-D-ribofuranosyl)-N.sup.6 -benzoyladenine,

9-(3',5'-di-O-trityl-.beta.-D-ribofuranosyl)-N.sup.2 -tritylguanine,

9-(3',5'-di-O-trityl-.beta.-D-ribofuranosyl)-N.sup.2 -acetylguanine,

9-(3',5'-di-O-trityl-.beta.-D-ribofuranosyl)-N.sup.2 -benzoylguanine,

9-(3',5'-di-O-trityl-.beta.-D-ribofuranosyl)-N.sup.2 -isobutyrlguanine,

9-(3',5'-di-O-trityl-.beta.-D-ribofuranosyl)purine,

9-(3',5'-di-O-trityl-.beta.-D-ribofuranosyl)-6-chloropurine,

9-(3',5'-di-O-trityl-.beta.-D-ribofuranosyl)-6-thiopurine,

9-(3',5'-di-O-trityl-.beta.-D-ribofuranosyl)-6-methylthiopurine,

9-(3',5'-di-O-trityl-.beta.-D-ribofuranosyl)-6-aminomethylpurine,

9-(3',5'-di-O-trityl-.beta.-D-ribofuranosyl)-6-dimethylaminopurine,

9-(3',5'-di-O-trityl-.beta.-D-ribofuranosyl)-2-aminopurine,

9-(3',5'-di-O-trityl-.beta.-D-ribofuranosyl)-2-acetamidopurine,

9-(3',5'-di-O-trityl-.beta.-D-ribofuranosyl)-2-benzamidopurine,

9-(3',5'-di-O-trityl-.beta.-D-ribofuranosyl)-2-isobutanamidopurine,

9-(3',5'-di-O-trityl-.beta.-D-ribofuranosyl)-2,6-diaminopurine,

9-(3',5'-di-O-trityl-.beta.-D-ribofuranosyl)-2,6-diacetamidopurine,

9-(3',5'-di-O-trityl-.beta.-D-ribofuranosyl)-2,6-dibenzamidopurine,

9-(3',5'-di-O-trityl-.beta.-D-ribofuranosyl)-2,6-diisobutanamidopurine,

9-(3',5'-di-O-trityl-.beta.-D-ribofuranosyl)-2-amino-6-chloropurine,

9-(3',5'-di-O-trityl-.beta.-D-ribofuranosyl)-2-amino-6-thiopurine,

9-(3',5'-di-O-trityl-.beta.-D-ribofuranosyl)-2-amino-6-methylthiopurine,

9-(3',5'-di-O-trityl-.beta.-D-ribofuranosyl)-2-fluoropurine,

9-(3',5'-di-O-trityl-.beta.-D-ribofuranosyl)-2-fluoroadenine,

9-(3',5'-di-O-trityl-.beta.-D-ribofuranosyl)-2-fluorohypoxanthine,

9-(3',5'-di-O-trityl-.beta.-D-ribofuranosyl)-2-fluoro-6-thiopurine,

9-(3',5'-di-O-trityl-.beta.-D-ribofuranosyl)-2-fluoro-6-methylthiopurine,

9-(3',5'-di-O-trityl-.beta.-D-ribofuranosyl)-2-fluoro-6-aminomethylpurine, and

9-(3',5'-di-O-trityl-.beta.-D-ribofuranosyl)-2-fluoro-6-dimethylaminopurine .

Example 5

To a solution of 3',5'-di-O-trityl-1-benzylinosine (2.0 g, 2.4 mmol), 4-dimethylaminopyridine (290 mg, 2.4 mmol) and triethylamine (480 mg, 4.8 mmol) in methylene chloride (40 mL) is added triflyl chloride (800 mg, 4.8 mmol), and the mixture is stirred at room temperature for 1 hour, and then concentrated in vacuo. The residue is chromatographed on a silica gel column using a mixture of tetrachloromethane and ethyl acetate (5:1 v/v) as the eluent to give 3',5'-di-O-trityl-2'-O-triflyl-1-benzylinosine as a foam (1.82 g, 78% yield), .sup.1 H NMR (Me.sub.2 SO-d.sub.6) .delta. 2.92-2.96 (2H, m, H-5',5"), 3.62-3.69 (1H, m, H-4'), 4.41-4.43 (1H, m, H-3'), 5.23 (2H, s, CH.sub.2 Ph), 5.89-5.95 (1H, m, H-2'), 6.66 (1 H, d, H-1', J.sub.1',2' =6.3 Hz), 7.18-7.34 (35H, m, 2 x Tr and CH.sub.2 Ph), 8.29, 8.32 (1H each, s, H-2, H-8). Analyses calculated for C.sub.56 H.sub.45 F.sub.3 N.sub.4 O.sub.5 S: C, 68.98, H, 4.65, N, 5.63. Found: C, 68.94, H, 4.76, N, 5.63.

By following the same procedure but using the corresponding 3',5'-di-O-trityl nucleosides, the following 2'-O-triflyl-3',5'-di-O-trityl nucleosides are prepared:

9-(2'-O-triflyl-3',5'-di-O-trityl-.beta.-D-ribofuranosyl)-hypoxanthine,

9-(2'-O-triflyl-3',5'-di-O-trityl-.beta.-D-ribofuranosyl)-2-fluoro-hypoxant hine,

9-(2'-O-triflyl-3',5'-di-O-trityl-.beta.-D-ribofuranosyl)-6-thio-hypoxanthi ne,

9-(2'-O-triflyl-3',5'-di-O-trityl-.beta.-D-ribofuranosyl)-N.sup.6 -trityladenine,

9-(2'-O-triflyl-3',5'-di-O-trityl-.beta.-D-ribofuranosyl)-N.sup.6 -acetyladenine,

9-(2'-O-triflyl-3',5'-di-O-trityl-.beta.-D-ribofuranosyl)-N.sup.6 -benzoladenine,

9-(2'-O-triflyl-3',5'-di-O-trityl-.beta.-D-ribofuranosyl)-N.sup.2 -tritylguanine,

9-(2'-O-triflyl-3',5'-di-O-trityl-.beta.-D-ribofuranosyl)-N.sup.2 -acetylguanine,

9-(2'-O-triflyl-3',5'-di-O-trityl-.beta.-D-ribofuranosyl)-N.sup.2 -isobutyrylguanine,

9-(2'-O-triflyl-3',5'-di-O-trityl-.beta.-D-ribofuranosyl)-N.sup.2 -benzoylguanine,

9-(2'-O-triflyl-3',5'-di-O-trityl-.beta.-D-ribofuranosyl)-N.sup.2 -trityl-6-thioguanine,

9-(2'-O-triflyl-3',5'-di-O-trityl-.beta.-D-ribofuranosyl)-6-thio-N.sup.2 -acetylguanine,

9-(2'-O-triflyl-3',5'-di-O-trityl-.beta.-D-ribofuranosyl)-6-thio-N.sup.2 -benzoylguanine,

9-(2'-O-triflyl-3',5'-di-O-trityl-.beta.-D-ribofuranosyl)-6-thio-N.sup.2 -isobutyrylguanine,

9-(2'-O-triflyl-3',5'-di-O-trityl-.beta.-D-ribofuranosyl)-purine,

9-(2'-O-triflyl-3',5'-di-O-trityl-.beta.-D-ribofuranosyl)-6-chloropurine,

9-(2'-O-triflyl-3',5'-di-O-trityl-.beta.-D-ribofuranosyl)-6-thiopurine,

9-(2'-O-triflyl-3',5'-di-O-trityl-.beta.-D-ribofuranosyl)-6-methylthiopurin e,

9-(2'-O-triflyl-3',5'-di-O-trityl-.beta.-D-ribofuranosyl)-6-aminomethylpuri ne,

9-(2'-O-triflyl-3',5'-di-O-trityl-.beta.-D-ribofuranosyl)-6-dimethylaminopu rine,

9-(2'-O-triflyl-3',5'-di-O-trityl-.beta.-D-ribofuranosyl)-2-aminopurine,

9-(2'-O-triflyl-3',5'-di-O-trityl-.beta.-D-ribofuranosyl)-2-acetamidopurine

9-(2'-O-triflyl-3',5'-di-O-trityl-.beta.-D-ribofuranosyl)-2-benzamidopurine

9-(2'-O-triflyl-3',5'-di-O-trityl-.beta.-D-ribofuranosyl)-2-isobutanamidopu rine,

9-(2'-O-triflyl-3',5'-di-O-trityl-.beta.-D-ribofuranosyl)-2,6-diaminopurine

9-(2'-O-triflyl-3',5'-di-O-trityl-.beta.-D-ribofuranosyl)-2,6-diacetamidopu rine,

9-(2'-O-triflyl-3',5'-di-O-trityl-.beta.-D-ribofuranosyl)-2,6-dibenzamidopu rine,

9-(2'-O-triflyl-3',5'-di-O-trityl-.beta.-D-ribofuranosyl)-2,6-diisobutanami dopurine,

9-(2'-O-triflyl-3',5'-di-O-trityl-.beta.-D-ribofuranosyl)-2-amino-6-chlorop urine,

9-(2'-O-triflyl-3',5'-di-O-trityl-.beta.-D-ribofuranosyl)-2-amino-6-thiopur ine,

9-(2'-O-triflyl-3',5'-di-O-trityl-.beta.-D-ribofuranosyl)-2-amino-6-methylt hiopurine,

9-(2'-O-triflyl-3',5'-di-O-trityl-.beta.-D-ribofuranosyl)-2-fluoropurine,

9-(2'-O-triflyl-3',5'-di-O-trityl-.beta.-D-ribofuranosyl)-2-fluoroadenine,

9-(2'-O-triflyl-3',5'-di-O-trityl-.beta.-D-ribofuranosyl)-2-fluorohypoxanth ine,

9-(2'-O-triflyl-3',5'-di-O-trityl-.beta.-D-ribofuranosyl)-2-fluoro-6-thiopu rine,

9-(2'-O-triflyl-3',5'-di-O-trityl-.beta.-D-ribofuranosyl)-2-fluoro-6-methyl thiopurine,

9-(2'-O-triflyl-3',5'-di-O-trityl-.beta.-D-ribofuranosyl)-2-fluoro-6-aminom ethylpurine,

9-(2'-O-triflyl-3',5'-di-O-trityl-.beta.-D-ribofuranosyl)-2-fluoro-6-dimeth ylaminopurine,

9-(3'-O-triflyl-2',5'-di-O-trityl-.beta.-D-ribofuranosyl)-purine,

9-(3'-O-triflyl-2',5'-di-O-trityl-.beta.-D-ribofuranosyl)-hypoxanthine,

9-(3'-O-triflyl-2',5'-di-O-trityl-.beta.-D-ribofuranosyl)-2-fluoro-hypoxant hine,

9-(3'-O-triflyl-2',5'-di-O-trityl-.beta.-D-ribofuranosyl)-6-thio-hypoxanthi ne,

9-(3'-O-triflyl-2',5'-di-O-trityl-.beta.-D-ribofuranosyl)-N.sup.6 -trityladenine,

9-(3'-O-triflyl-2',5'-di-O-trityl-.beta.-D-ribofuranosyl)-N.sup.6 -acetyladenine,

9-(3'-O-triflyl-2',5'-di-O-trityl-.beta.-D-ribofuranosyl)-N.sup.6 -benzoyladenine,

9-(3'-O-triflyl-2',5'-di-O-trityl-.beta.-D-ribofuranosyl)-N.sup.2 -tritylguanine,

9-(3'-O-triflyl-2',5'-di-O-trityl-.beta.-D-ribofuranosyl)-N.sup.2 -acetylguanine,

9-(3'-O-triflyl-2',5'-di-O-trityl-.beta.-D-ribofuranosyl)-N.sup.2 -benzoylguanine,

9-(3'-O-triflyl-2',5'-di-O-trityl-.beta.-D-ribofuranosyl)-N.sup.2 -isobutyrylguanine,

9-(3'-O-triflyl-2',5'-di-O-trityl-.beta.-D-ribofuranosyl)-N.sup.2 -trityl-6-thioguanine,

9-(3'-O-triflyl-2',5'-di-O-trityl-.beta.-D-ribofuranosyl)-6-thio-N.sup.2 -acetylguanine,

9-(3'-O-triflyl-2',5'-di-O-trityl-.beta.-D-ribofuranosyl)-6-thio-N.sup.2 -benzoylguanine,

9-(3'-O-triflyl-2',5'-di-O-trityl-.beta.-D-ribofuranosyl)-6-thio-N.sup.2 -isobutyrylguanine,

9-(3'-O-triflyl-2',5'-di-O-trityl-.beta.-D-ribofuranosyl)-6-chloropurine,

9-(3'-O-triflyl-2',5'-di-O-trityl-.beta.-D-ribofuranosyl)-6-thiopurine,

9-(3'-O-triflyl-2',5'-di-O-trityl-.beta.-D-ribofuranosyl)-6-methylthiopurin e,

9-(3'-O-triflyl-2',5'-di-O-trityl-.beta.-D-ribofuranosyl)-6-aminomethylpuri ne,

9-(3'-O-triflyl-2',5'-di-O-trityl-.beta.-D-ribofuranosyl)-6-dimethylaminopu rine,

9-(3'-O-triflyl-2',5'-di-O-trityl-.beta.-D-ribofuranosyl)-2-aminopurine,

9-(3'-O-triflyl-2',5'-di-O-trityl-.beta.-D-ribofuranosyl)-2,6-diaminopurine

9-(3'-O-triflyl-2',5'-di-O-trityl-.beta.-D-ribofuranosyl)-2-amino-6-chlorop urine,

9-(3'-O-triflyl-2',5'-di-O-trityl-.beta.-D-ribofuranosyl)-2-amino-6-thiopur ine,

9-(3'-O-triflyl-2',5'-di-O-trityl-.beta.-D-ribofuranosyl)-2-amino-6-methylt hiopurine,

9-(3'-O-triflyl-2',5'-di-O-trityl-.beta.-D-ribofuranosyl)-2-fluoropurine,

9-(3'-O-triflyl-2',5'-di-O-trityl-.beta.-D-ribofuranosyl)-2-fluoroadenine,

9-(3'-O-triflyl-2',5'-di-O-trityl-.beta.-D-ribofuranosyl)-2-fluorohypoxanth ine,

9-(3'-O-triflyl-2',5'-di-O-trityl-.beta.-D-ribofuranosyl)-2-fluoro-6-thiopu rine,

9-(3'-O-triflyl-2',5'-di-O-trityl-.beta.-D-ribofuranosyl)-2-fluoro-6-methyl thiopurine,

9-(3'-O-triflyl-2',5'-di-O-trityl-.beta.-D-ribofuranosyl)-2-fluoro-6-aminom ethylpurine, and

9-(3'-O-triflyl-2',5'-di-O-trityl-.beta.-D-ribofuranosyl)-2-fluoro-6-dimeth ylaminopurine.

Example 6

To a solution of 2'-O-triflyl-3',5'-di-O-trityl-1-benzylinosine (3.24 g, 3.32 mmol) in dry methylene chloride (40 mL) is added a solution of TASF (2.75 g, 10 mmol) in methylene chloride (20 mL) in an argon atmosphere at -70.degree. C. The reaction mixture is allowed to warm to room temperature, and stirring contained for 4 days. An additional amount of TASF (5.0 g, 20 mmol) in methylene chloride (40 mL) is charged at -40.degree. C. on the second and third days. The reaction is quenched by addition of water (50 mL). The organic layer is separated, washed with water (2.times.75 mL), dried over sodium sulfate, and concentrated in vacuo. The residue is chromotographed on a silica gel column using n-hexane-ethyl acetate (4:1 v/v) as the initial eluent followed by n-hexane-ethyl acetate (2:1 v/v) to give 9-(2'deoxy-2'-fluoro-3',5'-di-O-trityl-.beta.-D-arabinofuranosyl)-1-benzyl hypoxanthine (842 mg, 30% yield) as a foam, .sup.1 H NMR (Me.sub.2 SO-d.sub.6) .delta. 3.00-3.02 (2H, m, H-5',5"), (1H, dm, H-3', J.sub.3',F =19.5 Hz), 4.39 (1H, m, H-4'), 4.44 (1H, dm, H-2', J.sub.2',F =50 0 Hz), 5.24 (2H, s, CH.sub.2 Ph) , 6.37 (1H, dd, H-1', J.sub.1',2' =3.0, J.sub.1',F=22.0 Hz), 7.27-7.32 (35H, m, 2 x Tr and Ch.sub.2 Ph), 7.72 (1H, d, H-8, J.sub.8,F =2.2 Hz), 8.56 (1H, s, H-2). Analyses calculated for C.sub.55 H.sub.45 FN.sub.4 O.sub.4.1/5CHCl: C, 76.31, H, 5.24, N, 6.45. Found: C, 76.45, H, 5.54, N, 6.23. A small amount of chloroform is detected in the .sup.1 H NMR of this analytical sample.

By following the same procedure but using the corresponding 2'-O-triflyl-3',5'-di-O-trityl nucleosides, the following 9-(2'-deoxy-2'-3',5'-di-O-trityl nucleosides are prepared in 6-30% yield:

9-(2'deoxy-2'-fluoro-3',5'-di-O-trityl-.beta.-D-arabinofuranosyl)-purine,

9-(2'deoxy-2'-fluoro-3',5'-di-O-trityl-.beta.-D-arabinofuranosyl)-thioguani ne,

9-(2'deoxy-2'-fluoro-3',5'-di-O-trityl-.beta.-D-arabinofuranosyl)-2-fluoroa denine,

9-(2'deoxy-2'-fluoro-3',5'-di-O-trityl-.beta.-D-arabinofuranosyl)-2-fluoroh ypoxanthine,

9-(2'deoxy-2'-fluoro-3',5'-di-O-trityl-.beta.-D-arabinofuranosyl)-N.sup.6 -trityladenine,

9-(2'deoxy-2'-fluoro-3',5'-di-O-trityl-.beta.-D-arabinofuranosyl)-N.sup.6 -acetyladenine,

9-(2'deoxy-2'-fluoro-3',5'-di-O-trityl-.beta.-D-arabinofuranosyl)-N.sup.6 -benzoyladenine,

9-(2'deoxy-2'-fluoro-3',5'-di-O-trityl-.beta.-D-arabinofuranosyl)-hypoxanth ine,

9-(2'deoxy-2'-fluoro-3',5'-di-O-trityl-.beta.-D-arabinofuranosyl)-guanine,

9-(2'deoxy-2'-fluoro-3',5'-di-O-trityl-.beta.-D-arabinofuranosyl)-N.sup.2 -acetylguanine,

9-(2'deoxy-2'-fluoro-3',5'-di-O-trityl-.beta.-D-arabinofuranosyl)-N.sup.2 -benzoylguanine,

9-(2'deoxy-2'-fluoro-3',5'-di-O-trityl-.beta.-D-arabinofuranosyl)-N.sup.2 -isobutyrylguanine,

9-(2'deoxy-2'-fluoro-3',5'-di-O-trityl-.beta.-D-arabinofuranosyl)-6-chlorop urine,

9-(2'deoxy-2'-fluoro-3',5'-di-O-trityl-.beta.-D-arabinofuranosyl)-6-thiopur ine,

9-(2'deoxy-2'-fluoro-3',5'-di-O-trityl-.beta.-D-arabinofuranosyl)-6-methylt hiopurine,

9-(2'deoxy-2'-fluoro-3',5'-di-O-trityl-.beta.-D-arabinofuranosyl)-6-aminome thylpurine,

9-(2'deoxy-2'-fluoro-3',5'-di-O-trityl-.beta.-D-arabinofuranosyl)-6-dimethy laminopurine,

9-(2'deoxy-2'-fluoro-3',5'-di-O-trityl-.beta.-D-arabinofuranosyl)-2-aminopu rine,

9-(2'deoxy-2'-fluoro-3',5'-di-O-trityl-.beta.-D-arabinofuranosyl)-2-acetami dopurine,

9-(2'deoxy-2'-fluoro-3',5'-di-O-trityl-.beta.-D-arabinofuranosyl)-2-benzami dopurine,

9-(2'deoxy-2'-fluoro-3',5'-di-O-trityl-.beta.-D-arabinofuranosyl)-2-isobyta namidopurine,

9-(2'deoxy-2'-fluoro-3',5'-di-O-trityl-.beta.-D-arabinofuranosyl)-2,6-diami nopurine,

9-(2'deoxy-2'-fluoro-3',5'-di-O-trityl-.beta.-D-arabinofuranosyl)-2,6-diace tamidopurine,

9-(2'deoxy-2'-fluoro-3',5'-di-O-trityl-.beta.-D-arabinofuranosyl)-2,6-diabe nzamidopurine,

9-(2'deoxy-2'-fluoro-3',5'-di-O-trityl-.beta.-D-arabinofuranosyl)-2,6-diiso butanamidopurine,

9-(2'deoxy-2'-fluoro-3',5'-di-O-trityl-.beta.-D-arabinofuranosyl)-2-amino-6 -chloropurine,

9-(2'deoxy-2'-fluoro-3',5'-di-O-trityl-.beta.-D-arabinofuranosyl)-2-amino-6 -thiopurine,

9-(2'deoxy-2'-fluoro-3',5'-di-O-trityl-.beta.-D-arabinofuranosyl)-2-amino-6 -methylthiopurine,

9-(2'deoxy-2'-fluoro-3',5'-di-O-trityl-.beta.-D-arabinofuranosyl)-2-fluorop urine,

9-(2'deoxy-2'-fluoro-3',5'-di-O-trityl-.beta.-D-arabinofuranosyl)-2-fluoroa denine,

9-(2'deoxy-2'-fluoro-3',5'-di-O-trityl-.beta.-D-arabinofuranosyl)-2-fluoroh ypoxanthine,

9-(2'deoxy-2'-fluoro-3',5'-di-O-trityl-.beta.-D-arabinofuranosyl)-2-fluoro- 6-thiopurine,

9-(2'deoxy-2'-fluoro-3',5'-di-O-trityl-.beta.-D-arabinofuranosyl)-2-fluoro- 6-methylthiopurine,

9-(2'deoxy-2'-fluoro-3',5'-di-O-trityl-.beta.-D-arabinofuranosyl)-2-fluoro- 6-aminomethylpurine, and

9-(2'deoxy-2'-fluoro-3',5'-di-O-trityl-.beta.-D-arabinofuranosyl)-2-fluoro- 6-dimethylaminopurine.

Treatment of 2'-O-triflyl nucleosides with fluorinating agents other than TASF, such as potassium fluoride in dimethylformamide, or tetra-n-butlammonium fluoride in tetrahydrofuran, Amberlyst A26 (F) in methylene chloride, or cesium fluoride in dimethylformamide afforded the corresponding 2'-fluoro-arabino nucleosides but in much smaller yields.

Example 7

To a solution of 3',5'-di-O-trityl-1-benzylinosine (4.3 g, 5.1 mmol) in dry methylene chloride (65 mL) is added a solution of DAST (2.02 mL, 15.3 mmol) in methylene chloride (65 mL) containing pyridine (3.7 mL, 50 mL) below -50.degree. C. while stirring. The mixture is allowed to warm to room temperature, and the stirring continued for 18 hours. The mixture is concentrated in vacuo, and the residue chromoatographed on a silica gel column using a mixture of petroleum ether and ethyl acetate (1:1 v/v) as the eluent to give 9-(2'-deoxy-2'-fluoro-3',5'-di-O-trityl-.beta.-D-arabinofuranosyl)-1-benzy lhypoxanthine (2.27 g, 52.6% yield) which has identified .sup.1 H NMR characteristics with that of an authentic sample obtained as described in Example 6.

By following the same procedure but using the corresponding 3',5'-di-O-trityl nucleosides, the 9-(2'-deoxy-2'-fluoro-3',5'-di-O-trityl-.beta.-D-arabinofuranosyl) nucleosides listed in Example 6 are prepared in 30-60% yield:

Example 8

To a stirring mixture of trifluoroacetic acid (61.3 mL) and chloroform (670 mL) is added 9-(2'-deoxy-2'-fluoro-3',5'-di-O-trityl-.beta.-D-arabinofuranosyl)-1-benzy lhypoxanthine (6.63 g, 7.85 mmol) at -25.degree. C. in an argon atmosphere. The mixture is allowed to warm to room temperature while stirring. After one hour at room temperature, the reaction mixture is cooled to -25.degree. C., and then diluted with ethanol (70 mL). The mixture is concentrated in vacuo, the residue triturated with a mixture of n-hexane and ethyl ether (1:1 v/v) (2.times.400 mL). The solid residue is dissolved in a minimum amount of ethanol chromatographed over a silica gel column using a mixture of chloroform and ethanol (1:1 v/v) as the eluent to give 9-(2'-deoxy-2'-fluoro-.beta.-D-arabinofuranosyl)-1-benzylhypoxanthine as a foam (2.5 g, 88% yield). .sup.1 H NMR (Me.sub.2 SO-d.sub.6) .delta. 3.68-3.92 (3h, m, H-4',5',5"), 4.44 (1H, ddd, H-3', J.sub.2',3' =4.4, J.sub.3',4' =4.9, J.sub.3',F =18.9 Hz), 5.23 (1h, ddd, H-2', J.sub.2',3' =4.7, J.sub.2',3' =4.4, J.sub.2',F 53.7 Hz), 5.24 (2H, s, CH.sub.2 Ph), 6.39 (dd, H-1', J.sub.1',2' =4.7, J.sub.1',F =13.5 Hz), 7.33 (5h, s, CH.sub.2 Ph), 8.26 (1H, d, H-8, J.sub.8,F =1.9 Hz), 8.62 (1H, s, H-2). Analyses calculated for C.sub.17 H.sub.17 FN.sub.4 O.sub.4.: C, 56.66, H, 4.75, N, 15.55. Found: C, 56.21, H, 4.91, N, 15.12.

By following the same procedure but using the corresponding nucleosides, the following 2'deoxy-2'-fluoro-.beta.-D-arabinofuranosyl) nucleosides are prepared.

9-(2'deoxy-2'-fluoro-.beta.-D-arabinofuranosyl)purine,

9-(2'deoxy-2'-fluoro-.beta.-D-arabinofuranosyl)thioguanine,

9-(2'deoxy-2'-fluoro-.beta.-D-arabinofuranosyl)-N.sup.6 -trityladenine,

9-(2'deoxy-2'-fluoro-.beta.-D-arabinofuranosyl)-N.sup.6 -acetyladenine,

9-(2'deoxy-2'-fluoro-.beta.-D-arabinofuranosyl)-N.sup.6 -benzoyladenine,

9-(2'deoxy-2'-fluoro-.beta.-D-arabinofuranosyl)hypoxanthine,

9-(2'deoxy-2'-fluoro-.beta.-D-arabinofuranosyl)-guanine,

9-(2'deoxy-2'-fluoro-.beta.-D-arabinofuranosyl)-N.sup.2 -acetylguanine,

9-(2'deoxy-2'-fluoro-.beta.-D-arabinofuranosyl)-N.sup.2 -benzoylguanine,

9-(2'deoxy-2'-fluoro-.beta.-D-arabinofuranosyl)-N.sup.2 -isobutyrylguanine,

9-(2'deoxy-2'-fluoro-.beta.-D-arabinofuranosyl)-6-chloropurine,

9-(2'deoxy-2'-fluoro-.beta.-D-arabinofuranosyl)-6-thiopurine,

9-(2'deoxy-2'-fluoro-.beta.-D-arabinofuranosyl)-6-methylthiopurine,

9-(2'deoxy-2'-fluoro-.beta.-D-arabinofuranosyl)-6-aminomethylpurine,

9-(2'deoxy-2'-fluoro-.beta.-D-arabinofuranosyl)-6-dimethylaminopurine,

9-(2'deoxy-2'-fluoro-.beta.-D-arabinofuranosyl)-2-aminopurine,

9-(2'deoxy-2'-fluoro-.beta.-D-arabinofuranosyl)-2-acetamidopurine,

9-(2'deoxy-2'-fluoro-.beta.-D-arabinofuranosyl)-2-benzamidopurine,

9-(2'deoxy-2'-fluoro-.beta.-D-arabinofuranosyl)-2-isobytanamidopurine,

9-(2'deoxy-2'-fluoro-.beta.-D-arabinofuranosyl)-2,6-diaminopurine,

9-(2'deoxy-2'-fluoro-.beta.-D-arabinofuranosyl)-2,6-diacetamidopurine,

9-(2'deoxy-2'-fluoro-.beta.-D-arabinofuranosyl)-2,6-dibenzamidopurine,

9-(2'deoxy-2'-fluoro-.beta.-D-arabinofuranosyl)-2,6-diisobutanamidopurine,

9-(2'deoxy-2'-fluoro-.beta.-D-arabinofuranosyl)-2-amino-6-chloropurine,

9-(2'deoxy-2'-fluoro-.beta.-D-arabinofuranosyl)-2-amino-6-thiopurine,

9-(2'deoxy-2'-fluoro-.beta.-D-arabinofuranosyl)-2-amino-6-methylthiopurine,

9-(2'deoxy-2'-fluoro-.beta.-D-arabinofuranosyl)-2-fluoropurine,

9-(2'deoxy-2'-fluoro-.beta.-D-arabinofuranosyl)-2-fluoroadenine,

9-(2'deoxy-2'-fluoro-.beta.-D-arabinofuranosyl)-2-fluorohypoxanthine,

9-(2'deoxy-2'-fluoro-.beta.-D-arabinofuranosyl)-2-fluoro-6-thiopurine,

9-(2'deoxy-2'-fluoro-.beta.-D-arabinofuranosyl)-2-fluoro-6-methylthiopurine

9-(2'deoxy-2'-fluoro-.beta.-D-arabinofuranosyl)-2-fluoro-6-aminomethylpurin e, and

9-(2'deoxy-2'-fluoro-.beta.-D-arabinofuranosyl)-2-fluoro-6-dimethylaminopur ine.

DISCUSSION

The inhibitory activity of F-ara-H (9-2'-fluoro-2'-deoxy-.beta.-D-arabinofuranosyl)-hypoxanthine against Leishmania tropica, as shown by Santi, et al., Pharm. Res., No. 5, September 1985, p. 217, prompted the preparation of large amounts of this compound for more detailed biological evaluation. The only available method was the procedure used in U.S. Pat. Nos. 4,751,221 and 4,918,179, which was very inefficient.

The present inventive synthesis started from the readily available natural nucleoside, inosine, which was first protected at the 3' and 5' positions, and then the 2' hydroxy group was triflated followed by treatment with a fluorinating agent such as potassium fluoride, tetrabutyl-ammonium fluoride, Amberlyst 26 (F.sup.- form) or tris(dimethylamino)-sulfur(trimethylsilyl)difluoride (TASF).

Acetyl, benzoyl, benzyl, tetahydropyranyl and silyl protecting groups were tested to protect the 3',5' positions. Such 3',5'-di-O-protected nucleosides were converted into their corresponding 2'-O-triflyl derivatives which were obtained generally in good yield. However, treatment of such 2'-O-triflyl nucleosides with potassium fluoride in dimethylformamide, tetrabutylammonium fluoride in dimethyl-formamide, Amberlyst 26 (F.sup.- form) in acetone or TASF in methylene chloride always produced a multi-component mixture from which 4,6-disubstituted furfuryl alcohol, 6-substituted 4-hydroxyfurfuryl alcohol, and purine base (products of elimination reaction) were isolated together with small amounts of untreated starting material and unfluorinated arabinosylpurine. Also treated were 3',5'-di-O-protected 2'unsubstituted purine nucleosides with diethylamino-sulfurtrifluoride (DAST). The reaction generally gave a mixture of many components from which the fluorinated product was isolated, after extremely laborious chromatographic separation, in only less than two percent yield at best.

It was found that unlike other 3'5'-di-O-protected derivatives, 5'-O-trityl nucleosides appeared to adapt the unusual .sup.2 T.sub.3 (D) twist conformation as evidenced by a large H-1' and H-2' coupling (J.sub.1',2' =6.3-7.2 Hz) in nuclear magnetic resonance spectroscopy. In this conformation, both the aglycon and 2'-O-triflyl group were in a quasi-equatorial disposition, which is not favorable for elimination reaction, leading to the formation of furfuryl alcohol derivatives. Also, the C2' position in this twisted conformation appeared to be least sterically hindered for the approach of the fluoride nucleophile. Indeed, after treatment of 5'-O-trityl-3'-O-acetyl-2'-O-triflyl-1-benzylinosine (see 2a, FIG. 1) with TASF, the desired 2'-"up"-fluorinated nucleoside (3a) was isolated in approximately 10% yield. Conversion of (3a) into F-ara-H proceeded very smoothly. The overall yield of F-ara-H by this procedure was several fold better than that of the original synthesis. Among several 5'-O-trityl-3'-protected-2' -O-triflyl-1-benzylinosine derivatives that were tested, the best result was obtained with 3',5'-di-O-trityl-2'-O-triflyl-1-benzylinosine (2b). When (2b) was treated with TASF, the desired fluorinated nucleoside (3b) was obtained in 30% yield. Again, deprotection of (3b) to F-ara-H occurred in high yield.

Treatment of 3',5'-di-O-trityl-1-benzylinosine (1b) with DAST afforded 60% yield of the fluorinated product (3b). Tri-O.sup.3',O.sup.5', N.sup.6 -trityladenosine, 3',5'-di-O-tritylinosine and 2-N-protected-3',5'-di-O-tritylguanosine also afforded their corresponding 2'-fluorinated arabinosyl nucleosides with somewhat lower yields.

Contact Me | Home