A convergent synthesis of the proposed structure of antitumor depsipeptide stereocalpin A.
The total synthesis of the proposed structure of anticancer agent stereocalpin A is described. The synthesis features a diastereoselective synthesis of a 5-hydroxy-2,4-dimethyl-3-oxooctanoic acid unit with asymmetric anti- and syn-aldol reactions as the key steps. Initial cycloamidation led to complete epimerization at the C-11 stereocenter due to unique steric constraints in the 12-membered depsipeptide ring. A late-stage methylation strategy led to the synthesis of the proposed structure of stereocalpin A.
Department of Chemistry, Purdue University, 560 Oval Drive, West Lafayette, Indiana 47907, USA. akghosh@purdue.edu
Arun K
AK
Ghosh
Chun-Xiao
CX
Xu
D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D047630:Depsipeptides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D015394:Molecular Structure; D019906:Nuclear Magnetic Resonance, Biomolecular; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1 / Q000037:antagonists & inhibitors; D013237:Stereoisomerism
D000970:Antineoplastic Agents; D047630:Depsipeptides; C540377:stereocalpin A; C516607:PTPN1 protein, human; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1