Asymmetric synthesis of (2S,3R)-capreomycidine and the total synthesis of capreomycin IB.
A 27 step total synthesis of the tuberculostatic macrocyclic peptide antibiotic capreomycin IB has been accomplished. The synthesis features the use of an enolate-aldimine condensation between a chiral glycine aluminum enolate and the benzyl imine of 3-tert-butyldimethylsiloxy-propanal as a means of preparing the cyclic guanidine amino acid (2S,3R)-capreomycidine. Additionally, a Hofmann rearrangement was exacted on a late-stage pentapeptide in order to transform an asparagine residue into a diaminopropanoic acid residue.
DeMong
Duane E
DE
Department of Chemistry, Colorado State University, Fort Collins, Colorado 80523, USA.
Williams
Robert M
RM
D000900:Anti-Bacterial Agents / Q000138:chemical synthesis*; D001120:Arginine / Q000031:analogs & derivatives* / Q000138:chemical synthesis*; D002207:Capreomycin / Q000138:chemical synthesis*; D013237:Stereoisomerism
D000900:Anti-Bacterial Agents; C463580:capreomycidine; D002207:Capreomycin; D001120:Arginine