Development of new synthetic methodologies and their applications to the total synthesis of natural products were studied. In the course of synthesis of tricyclo-[4.3.2.$0^{1,5}$] undecane structure, unusual 6-exo radical cyclization was observed. Most of 2,2-disubstituted cyclopentene derivatives cyclized to produce tricyclo-[4.3.2.$0^{1,5}$] undecane through radical reaction sequence, which involved cyclopropyl methyl radical mediated rearrangement. However, in the case of 146a, unusual 6-exo-radical cyclization proceeded due to stereochemistry of secondary hydroxyl group.
Tricyclic 151, prepared from β-keto ester 136, was used as a key intermediate for the total synthesis of Nopsan-4-ol. 151 was converted to Nopsan-4-ol by introduction of methyl group via 1,4-addition at C-6, methylation at C-4 position, and stereoselective reduction of olefin.
Synthetic method used in the construction of tricyclo-[4.3.2.$0^{1,5}$] undecane was also applied to the total synthesis of Delnudine. BC-ring of Delnudine was prepared through that radical cyclization and rearrangement. After manipulation of functional groups of B-ring, A-ring of Delnudine was prepared through a regioselective alkylidene carbene C-H insertion derived from alkylation of trimethylsilyl-diazomethyl lithium followed by Peterson olefination and α -elimination, and then ozonolysis followed by aldol condensation of resulting cyclopentene. Some manipulations of A-ring were studied to introduce a functional group on unactivated C-18 position. A noteworthy aspect of this synthesis is a one-pot construction of tricyclic ring system.
