26 (-)-β-ピネンから(+)-ヌートカトンの短段階合成

抄録

(+)-Nootkatone (1), an eremophilanoid isolated first from the heartwood of Alaska yellow cedar (Chamaecyparis nootkatensis), has been recognized as the key flavor constituent of grapefruit. An highly efficient and stereoselective synthesis of (+)-(1) has been accomplished starting with (+)-nopinone (2) as described below. Although the Michael reaction of silyl enol ether (3) and 3-penten-2-one gave only undesired dione (4) which was culminated in the synthesis of (+)-4-epinootkatone (7), the conjugate addition of methallyltrimethylsilane (11b) to trans-3-ethylidenenopinone (I), which was obtained from (2) on the cross condensation with acetaldehyde followed by acid treatment, afforded an adduct (15a) as the predominant product with the desired stereochemistry. Dione (14), obtained from the adduct on methylation followed by ozonization, afforded nootkatone hydrochloride (17) on treatment with hydrogen chloride. Regioselective dehydrochlorination of the hydrochloride yielded (1). An alternative route in which allyltrimethylsilane (11a) was used has also been studied.