Journal article
Total synthesis of (+)-schweinfurthins B and E
Journal of organic chemistry, Vol.74(18), pp.6965-6972
09/18/2009
DOI: 10.1021/jo901161m
PMID: 19697910
Abstract
The first total synthesis of (+)-schweinfurthin B, a potent and differentially active cytotoxic agent, has been accomplished. Completion of the synthesis required just 16 steps in the longest linear sequence from commercially available vanillin. Key synthetic transformations included a Shi epoxidation and an efficient cascade cyclization initiated by treatment of the resulting epoxide with BF(3).OEt(2). Furthermore, use of a methyl ether as a stable protecting group for benzylic alcohols dramatically increased the efficiency of the overall sequence. The benzylic ether can be removed from this electron-rich aromatic system through oxidation with DDQ that provided the desired aldehyde intermediate in quantitative yield and shortened the synthetic sequence. Introduction of the A-ring diol in the required cis stereochemistry then became viable through a short sequence highlighted by an aldol condensation with benzaldehyde to introduce an olefin as a latent carbonyl group at the C-3 position. This synthesis established for the first time the absolute stereochemistry of the natural product, and provides access to material on a scale that will advance biological studies. The total synthesis of the closely related compound (+)-schweinfurthin E also is reported.
Details
- Title: Subtitle
- Total synthesis of (+)-schweinfurthins B and E
- Creators
- Joseph J Topczewski - Department of Chemistry University of Iowa, Iowa City, Iowa 52242-1294, USAJeffrey D NeighborsDavid F Wiemer
- Resource Type
- Journal article
- Publication Details
- Journal of organic chemistry, Vol.74(18), pp.6965-6972
- DOI
- 10.1021/jo901161m
- PMID
- 19697910
- NLM abbreviation
- J Org Chem
- ISSN
- 0022-3263
- eISSN
- 1520-6904
- Publisher
- United States
- Language
- English
- Date published
- 09/18/2009
- Academic Unit
- Neuroscience and Pharmacology; Chemistry
- Record Identifier
- 9983985912502771
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