STUDIES DIRECTED TOWARD THE TOTAL SYNTHESIS OF BRUCEANTIN (TRANS-AXIAL-DIOL, TETRAHYDROFURAN)

FENG-JIUN KUO, Purdue University

Abstract

The results of research on a general approach to the total synthesis of Bruceantin are detailed. The original approach started from the ABC ring tricyclic carboxylate enone was found to be troublesome. Although an additional unsaturation could be smoothly incorporated, it was difficult to effect the conversion of this dienone to the requisite C-7 alcohol. A modification of the above strategy allowed synthesis of the C-7 alcohol. This modified strategy involved: (1) Lewis-acid-induced michael reaction to an enone phosphonate, (2) conversion of the enone to an epoxy ketone, (3) intramolecular Wadsworth-Emmons reaction to form an (gamma),(delta)-epoxy enone, (4) LAH reduction followed by PDC oxidation to give a (delta)-hydroxy enone, and finally (5) Birch reduction of the (delta)-hydroxy enone to produce a (delta)-hydroxy ketone. Thus the desired C-7 hydroxy ABC ring intermediate was prepared. In order to introduce D ring, a model study was investigated. The D-ring lactol was achieved via intramolecular alkylation of the alpha-bromo acetal derivative of the C-7 alcohol. The E-ring formation was also investigated on the same model system by using the oxygen atom of the C-8 methoxymethyl ether as a potential nucleophile. Preliminary results showed that the tetrahydrofuran ring was formed at the (gamma)-position instead of (alpha)-position of the corresponding C-ring (gamma)-bromovinyl nitrile. A similar tricyclic C-7 alcohol was also prepared from the readily available ABC ring (gamma)-hydroxy enone with the C-8 methyl alcohol protected as benzyl ether. The D ring lactol was introduced by using the same method described above and the E ring was achieved as follows: (1) conversion of the C-8 methoxybenzyl ether to a mesylate, (2) introduction of phenylselenyl group to the alpha position of the C-13 carbonyl group, (3) 1,2 addition of cyano anion to the C-13 carbonyl group followed by simultaneous intramolecular SN2 reaction to complete the E ring synthesis. Oxidation-Elimination afforded the unsaturated C ring. Finally the (DELTA)('11,12) double bond was converted to trans diol in three-step procedure: (1) osmylation to cis diol, (2) Swern oxidation of cis diol under non-basic condition to mono-hydroxy ketone, (3) alpha-face reduction of carbony to provide trans diol.

Degree

Ph.D.

Subject Area

Organic chemistry

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