苦味物質Amarolideの全合成

抄録

Amarolide, one of the representative quassinoids, is a tetracyclic terpenoid having a picrasane skeleton with 10 chiral centers. The first total synthesis of (±) -amarolide has been accomplished stereoselectively from a known tricyclic compound.
Orthoester Claisen rearrangement and lead tetraacetate oxidation were utilized as key reactions to prepare 12β-hydroxypicrasan-3-one, a compound which has the correct relative stereochemistry of all the six ring-juncture chiral centers of the picrasane skeleton.
This 12β-hydroxypicrasan-3-one was transformed into (±) -amarolide by 18 steps reactions, including the 1, 3-carbonyl transposition reactions, introduction of two hydroxyl groups at C-2 and C-11 positions, respectively, and an oxidation of the ether ring to afford δ-lactone.
The NMR spectral data of synthetic amarolide and its diacetate were completely identical with those of natural ones. Overall yield of this synthesis of (±) -amarolide from the known tricyclic compound by 35-step reactions was 0.2%.
As the transformation of amarolide into quassin has already been known, this synthesis constitutes also a formal synthesis of (±) -quassin.