Total synthesis of 1-156,602, a novel cyclic hexadepsipeptide antibiotic

✍ Scribed by Philippe L. Durette; Florence Baker; Peter L. Barker; Joshua Boger; Steven S. Bondy; Milton L. Hammond; Thomas J. Lanza; Arsenio A. Pessolano; Charles G. Caldwell

• Publisher: Elsevier Science
• Year: 1990
• Tongue: French
• Weight: 261 KB
• Volume: 31
• Category: Article
• ISSN: 0040-4039
• DOI: 10.1016/s0040-4039(00)88774-2

✦ Synopsis

The total synthesis of the naturally occurring cyclic hexadepsipeptide antibiotic L-156.602 (1) is L-156602 (l), isolated from cultums of Streptomyces spp. MA6348,2 represents a novel 19membered cyclic hexadepsipeptide antibiotic closely related to axinothricin~ and A83586C3b and, based on comparison of spectral data, apparently identical to PD 124.9664 The suuctum of 1 was determined by NMR spectroscopic and X-ray diffraction analysis,2 and its absolute stereochemistry established.2J The peptide backbone of 1 is comprised of Gly and five unusual amino acids [(B)-and CS)-~iz,6 m-and (S)-&hychoxy-Ala, and (2&3S)-3-hydroxy-Leu],

and is appended by a 14carbon tetrahydropyranylpropionic acid side chain containing five asymmetric centers.

We have previously reported asymmetric syntheses of the constituent amino acids597 and the lipophilic side chain,738 as well as studies on the semisynthetic modification of the natural product.9 In the present communication, we describe the design and execution of a fragment-condensation strategy to the macmPeptolide and incorporation of the 14-C side chain to achieve a total synthesis of this biologically interesting natural product.