TUMOR REMISSION--TAXOL AND CLOSE ANALOGS VIA SYNTHESIS

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DESCRIPTION (adapted from applicant's abstract): This proposal deals with approaches to the total synthesis of taxol using D-camphor as an inexpensive, enantiomerically pure commodity. The strategy is to produce the natural product as well as a series of analog structures which would be accessible by the synthetic route, but not from baccatin III itself. These analogs are deoxytaxol as well as the 3Beta-epimer and analogs based on the 2-deoxy-2,3-dehydro system. The proposal places a great deal of emphasis on joining two ends of the molecule through an organometallic addition reaction and establishing a precursor to the total skeleton via an oxy-Cope rearrangement. When that would be accomplished, it would generate not the ring system of taxol itself, but a structure in which the A ring is 5-membered and the B ring is 9- membered. This in turn necessitates rearrangement to expand the A ring and contract the B ring. Ways to bring that about have been proposed.