In:
Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 101, No. 33 ( 2004-08-17), p. 12058-12063
Abstract:
A highly convergent total synthesis of the potent anticancer agent (+)-phorboxazole A ( 1 ) is accomplished. Four components ( 3 – 6 ) are assembled with considerations for control of absolute and relative stereochemistry. Iterative asymmetric allylation methodology addresses key stereochemical features in the preparation of the 2,6- cis - and 2,6- trans -tetrahydropyranyl rings of the C3–C19 component ( 3 ). The stereocontrolled asymmetric allylation process is also used for development of the C28–C41 fragment ( 4 ). Novel Barbier coupling reactions of α-iodomethyl oxazoles and related thiazoles are described with samarium iodide. The convergent assembly of components 4 and 5 features formation of the fully substituted C22–C26 pyran by intramolecular capture of an allyl cation intermediate with high facial selectivity, and further efforts lead to E -C19/C20 olefination. The synthesis culminates with use of a modified Julia olefination for attachment of the C42–C46 segment and subsequent late-stage macrocyclization by installation of the ( Z )-C2/C3 α,β-unsaturated lactone.
Type of Medium:
Online Resource
ISSN:
0027-8424
,
1091-6490
DOI:
10.1073/pnas.0402477101
Language:
English
Publisher:
Proceedings of the National Academy of Sciences
Publication Date:
2004
detail.hit.zdb_id:
209104-5
detail.hit.zdb_id:
1461794-8
SSG:
11
SSG:
12
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