Total synthesis of (-)-hennoxazole A.

Published

Journal Article

An enantioselective, convergent total synthesis of the antiviral marine natural product (-)-hennoxazole A is completed in 14 steps (longest linear sequence) from commercially available 4-methyloxazole-2-carboxylic acid. Synthesis of the C(1)-C(15) pyran/bisoxazole fragment takes advantage of an aldol-like coupling between a dimethyl acetal and an N-acetylthiazolidinethione for the direct, stereoselective installation of the C(8)-methoxy-bearing stereocenter. A one-pot acetoacetate acylation/decarboxylation/cyclodehydration of another elaborate thiazolidinethione allows for rapid assembly of the pyran-based ring system. Synthesis of the C(15)-C(25) skipped triene side chain fragment makes use of a [2,3]-Wittig-Still rearrangement for efficient installation of the trisubstituted Z-double bond. Key late-stage coupling of the two fragments is effected by deprotonation of the methyl group on the bisoxazole system using lithium diethylamide, followed by alkylation with an allylic bromide side chain segment to form the C(15)-C(16) bond.

Full Text

Duke Authors

Cited Authors

  • Smith, TE; Kuo, W-H; Balskus, EP; Bock, VD; Roizen, JL; Theberge, AB; Carroll, KA; Kurihara, T; Wessler, JD

Published Date

  • January 2008

Published In

Volume / Issue

  • 73 / 1

Start / End Page

  • 142 - 150

PubMed ID

  • 18052386

Pubmed Central ID

  • 18052386

Electronic International Standard Serial Number (EISSN)

  • 1520-6904

International Standard Serial Number (ISSN)

  • 0022-3263

Digital Object Identifier (DOI)

  • 10.1021/jo7018015

Language

  • eng