海洋産マンザミンアルカロイドナカドマリンＡの不斉全合成

Abstract

Manzamine alkaloid, (-) -nakadomarin A (1) was first isolated from the Okinawan marine sponge in 1997. Its structure consists of an unprecedented hexacyclic ring system (8/5/5/5/15/6) that includes a furan ring. We report here the first total synthesis of both enantiomers of nakadomarin A.The spiro-lactam 29, obtained from methyl 4-oxopiperidine carboxylate, was coupled with a furan ring by Suzuki-Miyaura reaction to give intermediate 30. Intramolecular cyclization of the furan ring to acyliminium cation afforded the central core of nakadomarin A, 32. Both 8- and 15-membered rings were constructed by ring closing metathesis (RCM) to give dioxonakadomarin A, 14 which was reduced to (±) -1. Using chiral 23, obtained by optical resolution, the asymmetric synthesis of unnatural enantiomer, (+) -1 has been accomplished and the synthesis confirmed the absolute stereochemistry of (-) -1.A central ABD ring system 52, which has all stereocenters of (-) -1, was synthesized from chiral hydroisoquinolinone 49, derived from Diels-Alder reaction of chiral piperidinone 47 and siloxydiene 48. The intermediate 52 was converted to natural (-) -nakadomarin A by furan formation via endoperoxides followed by RCM.