Silyl triflate-mediated ring-closure and rearrangement in the synthesis ofpotential bisfuran-containing intermediates of aflatoxin biosynthesis

The biosynthetic pathway to the potent mycotoxin aflatoxin B-1 is unusually long and complex, proceeding from anthraquinone to xanthone to coumarin nu clear types bearing fused tetrahydro- and bisdihydrofuran rings. A syntheti c strategy is described involving two silyl triflate-mediated cyclization a nd rearrangement processes that have enabled both furofuran oxidation state s to be readily achieved and undesired but thermodynamically favorable side reactions to be avoided in the preparation of these ring systems. In the f irst an o-methoxymethyl phenylacetaldehyde is cyclized directly to the five -membered, differentially protected hemiacetal, while in the second this gr oup, appropriately substituted, can be rearranged to a 4-trialkylsilyloxy-2 ,5-methano-l,3-benzodioxepane. The latter masked dialdehyde is sufficiently stable to strong base, mild acid, and oxidants to allow all needed aryl ri ng systems to be constructed. Using these methods, total syntheses of (+/-) -versicolorin B, (+/-)-versicolorin A, its hemiacetal, and its 6-deoxy deri vative, (+/-)-6-deoxyversicolorin A, have been achieved, and these are repo rted herein, as well as preparation of the methyl ester of a putative o-car boxybenzophenone biosynthetic intermediate. In work described elsewhere, in corporation experiments with C-13-labeled forms of these compounds have mad e possible the complete elucidation of bisfuran biosynthesis characteristic of the first major phase of aflatoxin formation in vivo.