Synthesis of eight stereoisomeric 5-(adenin-9-yl)-2,3,4-trihydroxypentanoic acids

Abstract

Condensation of 5-O-p-toluenesulfonyl-2,3-O-isopropylidene-D-ribonolactone (XIIIb) with sodium salt of adenine afforded compound XIV which on alkaline, followed by acid, hydrolysis gave the (2R,3R,4R)-isomer V. The (2S,3S,4S)-isomer VIII was prepared analogously from the L-ribonolactone derivative XVb via the adenine derivative XVI. Compound XVIIc was transformed by reaction with adenine into 6-(adenin-9-yl)-6-deoxy-D-glucose (XIX); similarly, 6-(adenin-9-yl)-6-deoxy-D-mannose (XXI) was prepared from the protected D-mannofuranoside XX. Oxidation of compounds XIX and XXI in alkaline medium afforded the (2S,3R,4R)-isomer VI, 1,2:3,4-di-O-isopropylidene-D-galactopyranose (XXIIa) was transformed into 6-(adenin-9-yl)-6-deoxy-D-galactose (XXIIIb) which was oxidatively cleaved to give the (2S,3S,4R)-isomer VII. Methyl 5,6-di-O-methanesulfonyl-2,3-O-isopropylidene-D-mannofuranoside (XXVIb) was transformed into the reactive L-gulofuranoside derivative XXVIIe which on condensation with adenine and oxidative cleavage gave the (2S,3R,4S)-isomer IX. The (2R,3S,4R)-isomer XI was prepared analogously from the D-gulofuranose derivative XXXIb. Starting from L-mannose, the (2R,3S,4S)-derivative X was prepared via the 6-(adenin-9-yl)-6-deoxy-L-mannofuranoside derivative XXXc. Methyl 5-O-p-toluenesulfonyl-2,3-O-isopropylidene-L-lyxofuranoside XXXVb was transformed into 5-(adenin-9-yl)-5-deoxy-2,3-O-isopropylidene-L-lyxofuranose (XXXVII) which was oxidized to the lactone XXXVIII; this compound on successive alkaline and acid hydrolysis afforded the (2R,3R,4S)-isomer XII.