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8‐Azaguanine 2′,3′‐Dideoxyribonucleosides: Glycosylation of the 5‐amino‐7‐methoxy‐3 H ‐1,2,3‐triazolo[4,5‐ d ]pyrimidinyl anion with 2,3‐dideoxy‐ D ‐ glycero ‐pentofuranosyl chloride
Author(s) -
Seela Frank,
Mersmann Karin
Publication year - 1993
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.19930760603
Subject(s) - chemistry , anomer , pyrimidine , glycosylation , chloride , derivative (finance) , medicinal chemistry , stereochemistry , ribonucleoside , aqueous solution , organic chemistry , rna , biochemistry , financial economics , economics , gene
The synthesis of the regioisomeric 8‐azaguanine N 7 ‐, N 8 ‐, and N 9 ‐(β‐ D ‐2′,3′‐dideoxyribonucleosides) ( 1, 2 , and 3 , respectively) and of the diamino derivative 13 is described. The anion of 5‐amino‐7‐methoxy‐3 H ‐1,2,3‐triazolo[4,5‐ d ]pyrimidine ( 5 ) was glycosylated with 5‐ O ‐[( tert ‐butyl)dimethylsilyl]‐2,3‐dideoxy‐ D ‐ glycero ‐pentofuranosyl chloride ( 6 ; anomeric mixture), yielding the regioisomeric 2′,3′‐dideoxyribofuranosides as anomeric mixtures 7a/10a, 8a/11a , and 9a/12a . They were desilylated with Bu 4 NF in THF affording the 5‐amino‐7‐methoxy‐nucleosides 7b–12b . Treatment with aqueous NaOH gave the 8‐azaguanine β‐ D ‐2′,3′‐dideoxynucleosides 1–3 and their α‐ D ‐anomers 14–16 . The reaction of 7b with NH 3 /MeOH yielded the diamino compound 13 . The N‐glycosylic bond of 8‐aza‐2′,3′‐dideoxyguanosine ( 1 ) is four‐times more stable against acid than that of 2′,3′‐dideoxyguanosine. Compounds 1, 2 , and 13 were converted to their 5′‐triphosphates 17–19 which showed only modest inhibitory activity against HIV‐reverse transcriptase.