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9‐deazapurine nucleosides. The synthesis of certain N ‐5‐2′‐deoxy‐β‐D‐ erythro pentofuranosyl and N ‐5‐β‐D‐arabinofuranosylpyrrolo[3,2‐ d ]pyrimidines
Author(s) -
Girgis Nabih S.,
Cottam Howard B.,
Larson Steven B.,
Robins Roland K.
Publication year - 1987
Publication title -
journal of heterocyclic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.321
H-Index - 59
eISSN - 1943-5193
pISSN - 0022-152X
DOI - 10.1002/jhet.5570240354
Subject(s) - chemistry , pyrimidine , inosine , diastereomer , guanosine , stereochemistry , halogenation , purine , medicinal chemistry , adenosine , organic chemistry , biochemistry , enzyme
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‐5 H ‐pyrrolo[3,2‐ d ]pyrimidine (3) using 1‐chloro‐2‐deoxy‐3,5‐di‐ O ‐( p ‐toluoyl)‐α‐D ‐ erythro pentofuranose (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‐erythro pentofuranosyl)‐5 H ‐pyrrolo‐[3,2‐ d ]pyrimidine (4) and 2,4‐dichloro‐5‐(2,3,5‐tri‐ O ‐benzyl‐β‐D‐arabinofuranosyl‐5 H ‐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‐deoxy erythr opentofuranosyl) ‐5 H ‐pyrrolo[3,2‐ d ]pyrimidine (6) . Reaction of 4 with sodium hydroxide followed by dehalogenation afforded the inosine analog, 5‐(2‐deoxy‐β‐D‐ erythro pentofuranosyl) ‐5 H ‐pyrrolo[3,2‐ d ]pyrimidin‐4(3 H )‐one (9) . Treatment of 4 with sodium hydroxide followed by methanolic ammonia gave the guanosine analog, 2‐amino‐5‐(2‐deoxy‐β‐D‐ erythro pentofuranosyl) ‐5 H ‐pyrrolo[3,2‐ d ]pyrimidin‐4(3 H )‐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‐5 H ‐pyrrolo [3,2‐ d ]pyrimidin‐4(3 H )‐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 C 1 carbon by the anionic heterocyclic nitrogen (S N 2 mechanism).