An approach to the total synthesis of sinefungin.
Condensation of N6-benzoyl-2',3'-O-isopropylideneadenosine-5'-aldehyde with nitromethane followed by acid catalyzed acetylation and borohydride reduction leads to N6-benzoyl-9-(5,6-dideoxy-2,3-O-isopropylidene-6-nitro-beta-D-ribo-hexofuranosyl)adenine (4). A second nitroaldol condensation between 4 and N-benzyloxycarbonly-L-aspartic acid-beta-semialdehyde alpha-benzyl ester (5) followed by acetylation and borohydride reduction leads to a fully protected 6'-nitro modification of sinefungin and its C6'-epimer (7). Hydrolysis of the acetonide followed by sequential reduction of the benzyl derived protecting groups and the nitro group and debenzoylation leads to a modest yield of a 3:1 mixture of sinefungin (1) and 6'-episinefungin which can only be separated by analytical ion exchange chromatography.
D000241:Adenosine / Q000031:analogs & derivatives* / Q000138:chemical synthesis; D000935:Antifungal Agents / Q000138:chemical synthesis*; D002855:Chromatography, Thin Layer; D007202:Indicators and Reagents; D007536:Isomerism; D009682:Magnetic Resonance Spectroscopy
D000935:Antifungal Agents; D007202:Indicators and Reagents; D000241:Adenosine; C006235:sinefungin