The 2′‐deoxyribofuranose analog of the naturally occurring antibiotics SF‐2140 and neosidomycin were prepared by the direct glycosylation of the sodium salts of the appropriate indole derivatives, with 1‐chloro‐2‐ deoxy‐3,5‐di‐O‐p‐toluoyl‐α‐D‐erythropentofuranose (5). Thus, treatment of the sodium salt of 4‐methoxy‐1H‐ indol‐3‐ylacetonitrile (4a) with 5 provided the blocked nucleoside, 4‐methoxy‐1‐(2‐deoxy‐3,5‐di‐O‐p‐toluoyl‐β‐ D‐erythropentofuranosyl)‐1H‐indol‐3‐ylacetonitrile (6a), which was treated with sodium methoxide to yield the SF‐2140 analog, 4‐methoxy‐1‐(2‐deoxy‐β‐D‐erythropentofuranosyl)‐1H‐indol‐3‐ ylacetonitrile (7a). The neosidomycin analog (8) was prepared by treatment of the sodium salt of 1H‐indol‐3‐ylacetonitrile (4b) with 5 to obtain the blocked intermediate 1‐(2‐deoxy‐3,5‐di‐O‐p‐toluoyl‐β‐D‐erythropentofuranosyl) −1H‐indol‐3‐ylace‐tonitrile (6b) followed by sodium methoxide treatment to give 1‐(2‐deoxy‐β‐D‐erythropentofuranosyl)‐1H‐ indol‐3‐ylacetonitrile (7b) and finally conversion of the nitrile function of 7b to provide 1‐(2‐deoxy‐β‐D‐ erythropentofuranosyl)‐1H‐indol‐3‐ylacetamide (8). In a similar manner, indole (9a) and several other substituted indoles including 1H‐indole‐4‐carbonitrile (9b), 4‐nitro‐1H‐indole (9c), 4‐chloro‐1H‐indole‐2‐carboxamide (9d) and 4‐chloro‐1H‐indole‐2‐carbonitrile (9e) were each glycosylated and deprotected to provide 1‐(2‐deoxy‐β‐D‐erythropentofuranosyl)‐1H‐indole (11a), 1‐(2‐deoxy‐β‐D‐erythropentofuranosyl)‐1H‐indole‐4‐ carbonitrile (11b), 4‐nitro‐1‐(2‐deoxy‐β‐D‐erythropentofuranosyl)‐1H‐indole (11c), 4‐chloro‐1‐(2‐deoxy‐β‐D‐ erythropentofuranosyl)‐1H‐indole‐2‐carboxamide (11d) and 4‐chloro‐1‐(2‐deoxy‐β‐D‐erythropentofuranosyl)‐ 1H‐indole‐2‐carbonitrile (11e), respectively. The 2′‐deoxyadenosine analog in the indole ring system was prepared for the first time by reduction of the nitro group of 11c using palladium on carbon thus providing 4‐amino‐1‐(2‐deoxy‐β‐D‐erythropentofuranosyl)‐ 1H‐indole (16, 1,3,7‐trideaza‐2′‐deoxyadenosine).

C-Glycosylation of two guanine analogues, 9-deaza- and 7-deazaguanine, has been achieved under Friedel-Crafts conditions, providing a direct synthetic route to 9-deazaguanosine (4; 2-amino-7-beta-D-ribofuranosyl-5H-pyrrolo[3,2-d]pyrimidin-4(3H)-one) and 8-beta-D-ribofuranosyl-7-deazaguanine (16), respectively. This electrophilic C-glycosylation was applied successfully to six guanine and substituted-guanine analogues resulting in yields of approximately 50%. This represents the first reported C-ribosylation of preformed nitrogen heterocycles isosteric with guanine. These C-nucleosides were evaluated for their ability to provide protection against a lethal Semliki Forest virus infection in mice, relative to 7-thia-8-oxoguanosine which was used as a positive control. Two of the C-nucleosides, 2-amino-6-chloro-5-methyl-7-beta-D-ribofuranosyl-5H-pyrrolo [3,2-d]pyrimidin-4(3H)-one (12) and the corresponding 6-bromo derivative (13), showed good prophylactic activity in this virus model system.

Certain 4‐substituted 1H‐pyrrolo[2,3‐b]pyridines (7‐azaindoles) undergo a nucleophilic substitution‐rearrangement upon treatment with various primary amines at elevated temperatures to yield N‐1‐substituted 4‐amino‐1H‐pyrrolo[3,2‐c]pyridines (5‐azaindoles). Treatment of the same 7‐azaindoles with secondary amines under the same reaction conditions led to simple nucleophilic substitution products.

The reactions of (b(2-furanyl)-and ~-(2-thienyl)acrylonitrile with a variety of active methylene reagents are described. The investigations make several new pyran and pyranodiazole derivatives accessible. Heterocyrlen-Synthese mit a$-ungesattigten Nitrilen: Die Reaktion von p-(Z-Furanyl)-und p-(2-Thienyl)acrylonitrilen mit CH-ariden MethylenverbindungenReaktionen von P-(2-Furanyl)-und P-(2-Thienyl)acrylonitrilen mit verschiedenen CH-aciden Methylenverbindungen werden beschrieben. Die Untersuchungen erschlienen einige neue Pyranund Pyranodiazol-Derivate. cc,P-Unsaturated nitriles are versatile reagents which have been extensively utilized in heterocyclic synthesis '). Recently, we have reported different new approaches for the synthesis of pyran, pyrano [2,3-c]

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A number of 2,4‐disubstituted pyrrolo[3,2‐d]pyrimidine N‐5 nucleosides were prepared by the direct glycosylation of the sodium salt of 2,4‐dichloro‐5H‐pyrrolo[3,2‐d]pyrimidine (3) using 1‐chloro‐2‐deoxy‐3,5‐di‐O‐(p‐toluoyl)‐α‐D ‐erythropentofuranose (1) and 1‐chloro‐2,3,5‐tri‐O‐benzyl‐α‐D‐arabinofuranose (11). The resulting N‐5 glycosides, 2,4‐dichloro‐5‐(2‐deoxy‐3,5‐di‐O‐(p‐toluoyl) ‐β‐D‐erythropentofuranosyl)‐5H‐pyrrolo‐[3,2‐d]pyrimidine (4) and 2,4‐dichloro‐5‐(2,3,5‐tri‐O‐benzyl‐β‐D‐arabinofuranosyl‐5H ‐pyrrolo [3,2‐d)pyrimidine (12), served as versatile key intermediates from which the N‐7 glycosyl analogs of the naturally occurring purine nucleosides adenosine, inosine and guanosine were synthesized. Thus, treatment of 4 with methanolic ammonia followed by dehalogenation provided the adenosine analog, 4‐amino‐5‐(2‐deoxyerythropentofuranosyl) ‐5H‐pyrrolo[3,2‐d]pyrimidine (6). Reaction of 4 with sodium hydroxide followed by dehalogenation afforded the inosine analog, 5‐(2‐deoxy‐β‐D‐erythropentofuranosyl) ‐5H‐pyrrolo[3,2‐d]pyrimidin‐4(3H)‐one (9). Treatment of 4 with sodium hydroxide followed by methanolic ammonia gave the guanosine analog, 2‐amino‐5‐(2‐deoxy‐β‐D‐erythropentofuranosyl) ‐5H‐pyrrolo[3,2‐d]pyrimidin‐4(3H)‐one (10). The preparation of the same analogs in the β‐D‐arabinonucleoside series was achieved by the same general procedures as those employed for the corresponding 2′‐deoxy‐β‐D‐ribonucleoside analogs except that, in all but one case, debenzylation of the sugar protecting groups was accomplished with cyclohexene‐palladium hydroxide on carbon, providing 4‐amino‐5‐β‐D‐arabinofuranosyl‐5H‐pyrrolo [3,2‐d]pyrimidin‐4(3H)‐one (18). Structural characterization of the 2′‐deoxyribonucleoside analogs was based on uv and proton nmr while that of the arabinonucleosides was confirmed by single‐crystal X‐ray analysis of 15a. The stereospecific attachment of the 2‐deoxy‐β‐D‐ribofuranosyl and β‐D‐arabinofuranosyl moieties appears to be due to a Walden inversion at the C1 carbon by the anionic heterocyclic nitrogen (SN2 mechanism).

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