Total synthesis of the marine cyanobacterial cyclodepsipeptide apratoxin A

Proceedings of the National Academy of Sciences of the United States of America
Jiehao Chen, Craig J Forsyth

Abstract

A total synthesis of apratoxin A was developed. Apratoxin A, isolated from Lyngbya spp. cyanobacteria, is representative of a growing class of marine cyanobacterial cyclodepsipeptides wherein discrete polypeptide and polyketide domains are merged by ester and amide or amide-derived linkages. In the apratoxins, the N terminus of the peptide domain [(Pro)-(N-Me-Ile)-(N-Me-ala)-(O-Me-Tyr)-(moCys)] is a modified vinylogous cysteine that is joined to a novel ketide [3,7-dihydroxy-2,5,8,8-tetramethylnonanoic acid (Dtna)] by an acid-sensitive thiazoline. The C-terminal proline is esterified to a hindered hydroxyl vicinal to the ketide's tert-butyl terminus. Major synthetic challenges included assembly and maintenance the thiazoline-containing moiety and macrolide formation involving acylation of the C39 hydroxyl. The Dtna domain was assembled in the biogenetic direction beginning with a Brown allylation of trimethylacetaldehyde to establish the C39 alcohol configuration. Diastereofacial selective addition of a higher-order dimethylcuprate upon a ring-closing metathesis-derived alpha,beta-unsaturated valerolactone installed the C37 methyl-bearing center. A Paterson anti-aldol process was used to incorporate the remaining two ketide ste...Continue Reading

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Citations

Jul 28, 2012·The Journal of Organic Chemistry·Yi LiuYuguo Du
Oct 13, 2012·Organic Letters·Bradley D RobertsonDon M Coltart
Feb 14, 2006·Nature Chemical Biology·Hendrik LueschPeter G Schultz
Jun 15, 2010·Chemical Communications : Chem Comm·Wenhua LiDawei Ma
Sep 21, 2016·The Journal of Organic Chemistry·Zhuo-Ya MaoGuo-Qiang Lin
Jul 7, 2016·Chemical Communications : Chem Comm·Adrien Quintard, Jean Rodriguez
Nov 27, 2008·Chemistry, an Asian Journal·Yoshitaka NumajiriTakayuki Doi
Nov 17, 2010·Chemistry, an Asian Journal·Takayuki DoiKazuo Shin-ya
May 20, 2016·Molecular Cancer Therapeutics·Kuan-Chun HuangKenichi Nomoto
Feb 13, 2021·Bioscience, Biotechnology, and Biochemistry·Yuichi Masuda
May 13, 2009·The Journal of Organic Chemistry·Arnaud GillesFlorine Cavelier
May 1, 2021·Marine Drugs·Shaden A M KhalifaHesham R El-Seedi
May 18, 2021·Organic & Biomolecular Chemistry·Oliver Andler, Uli Kazmaier
Sep 17, 2014·The Journal of Organic Chemistry·Sayantan Das, Rajib Kumar Goswami
Aug 6, 2014·The Journal of Organic Chemistry·Yuichi MasudaTakayuki Doi

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