Preliminary studies in the total synthesis of verrucarol
Turner, Richard B.
Master of Arts
A preliminary investigation was undertaken to find a route to the cis A-B ring fusion of the sesquiterpene alcohol verrucarol. To synthesize the desired cis-lactone (47), methylacetoacetate (60) was alkylated with methyl-2-bromopropionate (62) to give compound (64). Michael addition of (64) with methylvinylketone yielded (66). Acid catalyzed cyclization of (66) gave the unsaturated ketodiester (67). Although a second isomer, structure (68), could also be obtained; sodium borohydride reduction of (67) gave a 1,4-reduction leading to the saturated y-lactone (69) and not to the lactone (70). This reduction was confirmed by catalytic hydrogenation of (67) to the saturated ketodiester (75) and subsequent sodium borohydride reduction of (75) leading also to compound (69). Furthermore, the saturated ketodiester (75) was hydrolyzed and decarboxylated to the mono acid (76) which was converted to its corresponding methylester (77), hence also excluding the formation of compound (68) in the acid catalyzed cyclization. Meerwein-Ponndorf-Verley reduction on compound (67) failed to give the unsaturated lactone (46), which could have been equilibrated to the desired cis isomer (47).