Total Synthesis of Anti-HIV Agent Chloropeptin I

• Published in: Journal of the American Chemical Society Vol. 125; no. 30; pp. 9032 - 9034
• Main Authors: Deng, Hongbo, Jung, Jae-Kyung, Liu, Tao, Kuntz, Kevin W, Snapper, Marc L, Hoveyda, Amir H
• Format: Journal Article
• Language: English
• Published: WASHINGTON American Chemical Society 30.07.2003; Amer Chemical Soc
• Subjects: Anti-HIV Agents - chemical synthesis; Antibiotics. Antiinfectious agents. Antiparasitic agents; Antiviral agents; Biological and medical sciences; Chemistry; Chemistry, Multidisciplinary; Chlorophenols - chemical synthesis; Exact sciences and technology; Heterocyclic compounds; Heterocyclic compounds with n hetero atom and also o and/or s, se, te hetero atoms; Medical sciences; Organic chemistry; Peptides, Cyclic - chemical synthesis; Pharmacology. Drug treatments; Physical Sciences; Preparations and properties; Science & Technology; Stereoisomerism; SYSTEM; STREPTOMYCES SP; O-ARYLATION; COMPLESTATIN; ANTIBIOTICS; ENANTIOSELECTIVE SYNTHESIS; PHENYLBORONIC ACIDS; INHIBITING GP120-CD4 BINDING; FERMENTATION; STRUCTURE ELUCIDATION; Stereoselectivity; Enzyme inhibitor; Antiviral; Benzenic compound; Biological activity; Total synthesis; Oxygen nitrogen heterocycle
• ISSN: 0002-7863; 1520-5126
• DOI: 10.1021/ja030249r

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.