Ring opening of nucleoside 1',2'-epoxides with organoaluminum reagents: stereoselective entry to ribonucleosides branched at the anomeric position.
Epoxidation of 3',5'-O-(di-tert-butylsilylene)-1',2'-unsaturated uridine (11) with dimethyldioxirane proceeded from the alpha-face to give the 1',2'-alpha-epoxide 12. Upon reacting with organoaluminum reagents, the 1',2'-alpha-epoxide 12 underwent preferential syn-opening of the epoxide ring to yield the beta-anomers of 1'-methyl- (13beta), 1'-ethyl- (14beta), 1'-isobutyl- (15beta), 1'-ethynyl- (16beta), 1'-vinyl- (17beta), and 1'-phenyl- (18beta) uridine derivatives, although the corresponding alpha-anomers were also formed except for the reaction with triphenylaluminum. It was found, however, that protection of the N(3)-position of 11 either with a benzyloxymethyl or benzoyl group led to the exclusive formation of the desired beta-anomers. A possible explanation for the observed stereochemical outcome is presented. A similar strategy was found to be applicable to the synthesis of 1'-branched adenosine analogues, which include protected angustmycin C (37).
Haraguchi
Kazuhiro
K
School of Pharmaceutical Sciences, Showa University, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo 142-8555, Japan. harakazu@pharm.showa-u.ac.jp
Kubota
Yutaka
Y
Tanaka
Hiromichi
H
D000535:Aluminum / Q000737:chemistry*; D003500:Cyclization; D004852:Epoxy Compounds / Q000737:chemistry*; D015394:Molecular Structure; D009705:Nucleosides / Q000737:chemistry*; D009942:Organometallic Compounds / Q000737:chemistry*; D012263:Ribonucleosides / Q000138:chemical synthesis*; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D013730:Terphenyl Compounds / Q000737:chemistry; D014500:Uracil Nucleotides / Q000737:chemistry; D014529:Uridine / Q000737:chemistry
D004852:Epoxy Compounds; D009705:Nucleosides; D009942:Organometallic Compounds; D012263:Ribonucleosides; D013730:Terphenyl Compounds; D014500:Uracil Nucleotides; D000535:Aluminum; D014529:Uridine