Total synthesis of anti-HIV agent chloropeptin I

J Am Chem Soc. 2003 Jul 30;125(30):9032-4. doi: 10.1021/ja030249r.

Abstract

A convergent diastereo- and enantioselective total synthesis of anti-HIV agent chloropeptin I is reported. Important features of the total synthesis include: (1) the use of Ti-catalyzed cyanide addition to imines to prepare a requisite amino acid moiety, (2) the discovery of the positive effect of MeOH in the Cu-mediated biaryl ether formation to afford one of the two macrocyclic peptide moieties, and (3) the discovery of the positive influence of collidine in the diastereoselective Pd-mediated cross-coupling to result in efficient formation of another macrocycle within this medicinally important molecule. This key step is performed in the presence of four unprotected phenols, two of which reside on dichlorophenylglycines.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Anti-HIV Agents / chemical synthesis*
  • Chlorophenols / chemical synthesis*
  • Peptides, Cyclic / chemical synthesis*
  • Stereoisomerism

Substances

  • Anti-HIV Agents
  • Chlorophenols
  • Peptides, Cyclic
  • chloropeptin I