Synthetic studies of didemnins. IV. Synthesis of the macrocycle

✍ Scribed by William R. Ewing; Bruce D. Harris; Wen-Ren Li; Madeleine M. Joullie

• Book ID: 104233090
• Publisher: Elsevier Science
• Year: 1989
• Tongue: French
• Weight: 273 KB
• Volume: 30
• Category: Article
• ISSN: 0040-4039
• DOI: 10.1016/s0040-4039(01)80647-x

✦ Synopsis

A stereocontrolled route to the 23-membered macrocycle found in the didemnins is described.

As a continuation of our synthetic studies of the didemnins,z we now wish to report our synthesis of the didemnins' macrocycle. The didemnins (1) are a new class of depsipeptides originally isolated from a Caribbean (la) didemnin A, (lb) didemnln B, (lc) didemnin C, (ld) REH-HCI tunicate of the Didemnidae family (Trididemnum genus). 3a All didemnins contain the same parent macrocycle which is attached at the threonine nitrogen to N-methyl-D-leucine. This moiety, in turn, is found to be attached to lactic acid (didemnin C), lactylproline (didemnin B), or hydrogen (didemnin A). The interesting and varied biological activity of didemnins A and B has been the subject of many investigations.3 Antiviral, antitumor and immunosuppressive activities have been reported for these compounds. The crystal structure has been determined by X-ray analysis.4 Total syntheses5 and other synthetic studies have also been reporteda