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A convenient synthesis of 5‐substituted‐7‐β‐D‐arabinofuranosylpyrrolo[2,3‐ d ]pyrimidines structurally related to the antibiotics toyocamycin and sangivamycin
Author(s) -
Ramasamy Kandasamy,
Robins Roland K.,
Revankar Ganapathi R.
Publication year - 1988
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.5570250366
Subject(s) - chemistry , pyrimidine , acetylation , prodrug , stereochemistry , antibiotics , nucleoside , purine , combinatorial chemistry , organic chemistry , biochemistry , enzyme , gene
4‐Amino‐7‐(2,3,5‐tri‐ O ‐benzyl‐β‐D‐arabinofuranosyl)pyrrolo[2,3‐ d ]pyrimidine‐5‐carbonitrile ( 6a ), prepared from 2‐ethoxymethyleneamino‐5‐bromopyrrole‐3,4‐dicarbonitrile ( 4 ), was debenzylated with boron trichloride to give ara ‐toyocamycin ( 6b ). Further functional group transformation of 6b provided a route to 4‐amino‐7‐β‐D‐arabinofuranosylpyrrolo[2,3‐ d ]pyrimidine‐5‐thiocarboxamide ( ara ‐thiosangivamycin, 7a ), and the corresponding 5‐carboxamidoxime 8a and 5‐carboxamidine 8b derivatives. Phosphorylation of unprotected 7a with phosphorus oxychloride gave ara ‐thiosangivamycin 5′‐monophosphate ( 7b ). 2′‐ O ‐Acetyl‐ ara ‐thiosangivamycin ( 10b ) was prepared as a prodrug by acetylation of 9a , followed by deprotection of the t ‐butyldimethylsilyl groups under acidic conditions without acyl migration.