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Synthesis and Conformational Analysis of 1′‐ and 3′‐Substituted 2‐Deoxy‐2‐fluoro‐ D ‐ribofuranosyl Nucleosides
Author(s) -
Sivets Grigorii G.,
Kalinichenko Elena N.,
Mikhailopulo Igor A.
Publication year - 2007
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.200790191
Subject(s) - chemistry , anomer , pyrimidine , purine , stereochemistry , organic chemistry , enzyme
Convergent syntheses of the 9‐(3‐X‐2,3‐dideoxy‐2‐fluoro‐ β ‐ D ‐ribofuranosyl)adenines 5 (X=N 3 ) and 7 (X=NH 2 ), as well as of their respective α ‐anomers 6 and 8 , are described, using methyl 2‐azido‐5‐ O ‐benzoyl‐2,3‐dideoxy‐2‐fluoro‐ β ‐ D ‐ribofuranoside ( 4 ) as glycosylating agent. Methyl 5‐ O ‐benzoyl‐2,3‐dideoxy‐2,3‐difluoro‐ β ‐ D ‐ribofuranoside ( 12 ) was prepared starting from two precursors, and coupled with silylated N 6 ‐benzoyladenine to afford, after deprotection, 2′,3′‐dideoxy‐2′,3′‐difluoroadenosine ( 13 ). Condensation of 1‐ O ‐acetyl‐3,5‐di‐ O ‐benzoyl‐2‐deoxy‐2‐fluoro‐ β ‐ D ‐ribofuranose ( 14 ) with silylated N 2 ‐palmitoylguanine gave, after chromatographic separation and deacylation, the N 7 ‐ β ‐anomer 17 as the main product, along with 2′‐deoxy‐2′‐fluoroguanosine ( 15 ) and its N 9 ‐ α ‐anomer 16 in a ratio of ca. 42 : 24 : 10. An in‐depth conformational analysis of a number of 2,3‐dideoxy‐2‐fluoro‐3‐X‐ D ‐ribofuranosides (X=F, N 3 , NH 2 , H) as well as of purine and pyrimidine 2‐deoxy‐2‐fluoro‐ D ‐ribofuranosyl nucleosides was performed using the PSEUROT (version 6.3) software in combination with NMR studies.