P-14 Grayanotoxinの合成研究(ポスター発表の部)

抄録

Grayanotoxin is a toxic diterpenoid isolated from the leaves of Leucothoe grayana and has an interesting structure characterized by 5-7-6-5 ring system (grayanane skeleton). This diterpenoid shows potent biological activity increase in the membrane permeability to sodium ion. Herein, we wish to describe synthetic studies toward the total synthesis of grayanotoxin I using the sequential Michael-substitution reaction and fragmentation reaction in combination as key reactions. Sequential Michael-substitution reaction of ethyl α-bromoacrylate with the lithium enolate of cyclohexenone derivative (-)-16, which was obtained from the lipase-catalyzed enantioselective esterification of (±)-16, gave tricyclic compound 21 and 22. Both compounds 21 and 22 were converted to ester 27 via 23.. Reaction of the enolate of 27 with cyclopentenone 4, which was effectively synthesized starting from (-)-pantolactone (1) via 3, and from meso-diol 6, afforded 28 after deprotection of the silyl group. When 29 was treated with HClO_4 in CH_3CN, deprotection of the methoxymethyl group followed by fragmentation reaction occurred to give lactone 30 as a major product. Lactone 30 was converted to olefin 34 via 32 and 33. Synthesis of GTX-I from 34 is now in progress.