A concise total synthesis of (+)-FR900482 and (+)-FR66979.
The concise, enantioselective total synthesis of the potent antitumor antibiotics (+)-FR900482 and (+)-FR66979 are described. Sharpless asymmetric epoxidation technology has been deployed to construct the optically active aziridine-containing fragment that is joined to the aromatic moiety in a highly convergent manner. Dimethyldioxirane effects the remarkable one-step deprotection/oxidative cyclization of an eight-membered ring amino-ketone to the unique hydroxylamine hemiketal ring system that is a distinctive structural motif of FR900482. This reaction has been exploited in a concise 33-step enantioselective total synthesis of FR900482.
Judd
Ted C
TC
Department of Chemistry, Colorado State University, Fort Collins, Colorado 80523, USA.
Williams
Robert M
RM
D000903:Antibiotics, Antineoplastic / Q000138:chemical synthesis*; D006801:Humans; D015394:Molecular Structure; D010078:Oxazines / Q000138:chemical synthesis*; D013237:Stereoisomerism
D000903:Antibiotics, Antineoplastic; D010078:Oxazines; C053335:FR 900482; C058745:FR 66979