Total synthesis of antitumor depsipeptide (-)-doliculide.
[reaction: see text] (-)-Doliculide, a potent antitumor agent, is synthesized stereoselectively in a convergent manner. The key strategy involves a stereoselective synthesis of the polyketide unit and synthesis of the D-tyrosine derivative, followed by assembly of the fragments by an esterification and cycloamidation reaction sequence. The synthesis of the polyketide fragment was achieved by an iterative asymmetric synthesis to install stereoselectively both 1,3-dimethyl groups and the 1,3-diol unit by utilizing asymmetric cyclopropanations and Sharpless asymmetric epoxidations as the key steps.
Ghosh
A K
AK
Department of Chemistry, University of Illinois at Chicago, 60607, USA. arunghos@uic.edu
Liu
C
C
D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry; D003500:Cyclization; D047630:Depsipeptides; D015394:Molecular Structure; D010456:Peptides, Cyclic / Q000138:chemical synthesis* / Q000737:chemistry; D013237:Stereoisomerism; D014443:Tyrosine / Q000737:chemistry
D000970:Antineoplastic Agents; D047630:Depsipeptides; D010456:Peptides, Cyclic; C424144:doliculide; D014443:Tyrosine