抄録
Lycopodium alkaloids have unique skeletal characteristics and a variety of biological activities, such as acetylcholine esterase (AChE) inhibiton. These have inspires many groups to research on total syntheses of the Lycopodium alkaloids. Recently, we have investigated the alkaloidal constituents in Lycopodium serratum and have found several novel alkaloids including lycoposerramine-C (1), -X (3) and -Z (4). Herein, we report the first asymmetric total syntheses of these alkaloids. 1. Total synthesis of lycoposerramine-C (1) Lycoposerramine-C (1) idolated from L. serratum is a new fawcettimine-type Lycopodium alkaloid possessing a double bond at the C6-C7 positons in fawcettimine (2). In order to deelop an efficient synthetic route of 1, to exacute direct confirmation of its absolute configuration, and to supply it for the study of biological activity, we planned asymmetric total synthesis of 1. The successful synthesis involved a Co-mediated Pauson-Khand reaction, stereoselective reduction, and subsequent vinyl Claisen rearrangement as key steps. 2. Total syntheseses of lycoposerramine-X (3) and -Z (4) From spectroscopic analyses, new alkaloids, lycoposerramine-X (3) and -Z (4), were found to be diastereomeric isomers at C13 position of phlegmarine-type alkaloids, which consist of a piperidine ring with a novel nitron residue and an octahydroquinoline ring with four chiral centers. Starting from (R)-3-methylcyclohexanone, the first asymmetric total syntheses of these alkaloids were accomplihde, which involved Johnson-Claisen rearrangement, Mitsunobu reaction, and cyclic nitron formation. The syntheses enabled us to established the absolute configuration of 3 and 4.
