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3′‐Substituted and 2′,3′‐Unsaturated 7‐Deazaguanine 2′,3′‐Dideoxynucleosides: Syntheses and Inhibition of HIV‐1 Reverse Transcriptase
Author(s) -
Seela Frank,
Muth HeinzPeter
Publication year - 1991
Publication title -
helvetica chimica acta
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.74
H-Index - 82
eISSN - 1522-2675
pISSN - 0018-019X
DOI - 10.1002/hlca.19910740517
Subject(s) - chemistry , pyrimidine , nucleoside , nucleophile , stereochemistry , ribonucleoside , derivative (finance) , human immunodeficiency virus (hiv) , reverse transcriptase , nucleoside analogue , deoxyribonucleoside , enzyme , rna , organic chemistry , biochemistry , catalysis , virology , biology , financial economics , economics , gene
The syntheses of 2′,3′‐dideoxy‐2′,3′‐didehydro‐β‐ D ‐ribofuranoside 1 and 2′,3′‐dideoxy‐3′‐fluoro‐β‐ D ‐ribo‐furanoside 5 of 7‐deazaguanine as well as 7‐deaza‐2′‐deoxyxyloguanosine ( 3 ) are described. The corresponding 2,4‐diamino compounds 2 and 4 were also prepared. Thus, silytation of 2‐amino‐4‐chloro‐7‐(2‐deoxy‐β‐ D ‐ erythro ‐pentofuranosyl)‐7 H ‐pyrrolo[2,3‐ d ]pyrimidine ( 6 ) afforded 7 , which gave the oxo‐nucleoside 13 after oxidation with CrO 3 . NaBH 4 reduction yielded 14 which, upon deprotection (Bu 4 NF) and nucieophific displacement, afforded 3 and 4 . On the other hand, the N 2 ‐formyl derivative of 7 was mesylated (→ 10 ), treated with Bu 4 NF, and deprotected with NH 3 yielding the 2′,3′‐dideoxy‐2′,3′‐didehydro‐nucleoside 12 , Nucleophilic displacement reactions on 12 yielded 1 and 2 . The fluoro‐nucleoside 5 was obtained from 14 after methoxytritylation of the NH 2 group (→ 16 ), fluorination with DAST (→ 17), and treatment with 2M NaOH. The 5′‐triphosphates of 5 and other pyrrolo[2,3‐ d ]pyrimidine 2′,3′‐dideoxy‐3′‐fluoro‐nucleosides were found to be highly active inhibitors of HIV‐1. reverse transcriptase, similar to those of 1 and 2 .