Synthesis of 2',3'-dideoxy-2',3'-alpha-methanocytidine.
A six-stage synthesis of 2',3'-dideoxy-2',3'-alpha-methanocytidine (3) from (5S)-5-benzoyloxymethyl-(5H)-furan-2-one (5) is described. The key step involved the stereoselective formation of (1R,4S,5S)-4-benzoyloxymethyl-3-oxabicyclo[3.1.0]hexan-2-one (7) via 1,3-dipolar cycloaddition of diazomethane to 5 followed by photoinduced elimination of nitrogen. Reduction of 7 to the corresponding lactol followed by acetylation yielded primarily 1-O-acetyl-5-O-benzoyl-2,3-dideoxy-beta-D-ribofuranose (8). Reaction of 8 with 2,4-bis(trimethylsilyl)cytosine and EtAlCl2 followed by deprotection and chromatography gave 3, which exhibited only weak activity against the human immunodeficiency virus (HIV).
Beard
A R
AR
Department of Chemistry, Reading University, Whiteknights, Berkshire, Great Britain.
Butler
P I
PI
Mann
J
J
Partlett
N K
NK
D000998:Antiviral Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D006678:HIV / Q000187:drug effects; D009682:Magnetic Resonance Spectroscopy; D015394:Molecular Structure; D016047:Zalcitabine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology
D000998:Antiviral Agents; C067058:2',3'-dideoxy-2',3'-methanocytidine; D016047:Zalcitabine