期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2004
卷号：101
期号：33
页码：12067-12072
DOI：10.1073/pnas.0402752101
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：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
