Silyl Triflate-Mediated Ring-Closure and Rearrangement in the Synthesis of Potential Bisfuran-Containing Intermediates of Aflatoxin Biosynthesis
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- 作者：Todd L. Graybill ; Eduard G. Casillas ; Kollol Pal ; and Craig A. Townsend
- 刊名：Journal of the American Chemical Society
- 出版年：1999
- 出版时间：September 1, 1999
- 年：1999
- 卷：121
- 期：34
- 页码：7729 - 7746
- 全文大小：547K
- 年卷期：v.121,no.34(September 1, 1999)
- ISSN：1520-5126
文摘
The biosynthetic pathway to the potent mycotoxin aflatoxin B1 is unusually long and complex,proceeding from anthraquinone to xanthone to coumarin nuclear types bearing fused tetrahydro- andbisdihydrofuran rings. A synthetic strategy is described involving two silyl triflate-mediated cyclization andrearrangement processes that have enabled both furofuran oxidation states to be readily achieved and undesiredbut thermodynamically favorable side reactions to be avoided in the preparation of these ring systems. In thefirst an o-methoxymethyl phenylacetaldehyde is cyclized directly to the five-membered, differentially protectedhemiacetal, while in the second this group, appropriately substituted, can be rearranged to a 4-trialkylsilyloxy-2,5-methano-1,3-benzodioxepane. The latter masked dialdehyde is sufficiently stable to strong base, mild acid,and oxidants to allow all needed aryl ring systems to be constructed. Using these methods, total syntheses of(±)-versicolorin B, (±)-versicolorin A, its hemiacetal, and its 6-deoxy derivative, (±)-6-deoxyversicolorin A,have been achieved, and these are reported herein, as well as preparation of the methyl ester of a putativeo-carboxybenzophenone biosynthetic intermediate. In work described elsewhere, incorporation experimentswith 13C-labeled forms of these compounds have made possible the complete elucidation of bisfuran biosynthesischaracteristic of the first major phase of aflatoxin formation in vivo.