SYNTHESIS OF (-HYDROXYSEDAMINE AND (-)-HYDROXYSEDAMINE AND (+)-N-METHYLPSEUDOCONHYDRINE FROM S-GLUTAMIC ACID VIA HOMOCHIRAL ACYLIMINIUM ION())

Efficient syntheses of (+)-N-methylpseudoconhydrine (5) and (-)-hydrox ysedamine (10) are described starting from the readily available (2RS, 5S)-Methyl 5-(tert-butyldimethyl-silyloxy) -2-ethoxypiperidine-1-carbo xylate (1) and proceeding via homochiral acyliminium ion as an interme diate. Compounds 5 and 7b were obtained in 32 and 34 %, reap., overall yield from 1. After deprotection of the OH function of 3a, b the dias tereomeric mixture of 6a, b was separated and converted to pseudoconhy drine 7b and epi-pseudoconhydrine 7a, respectively. Reduction of the u rethane moiety of 3a, b followed by treatment with hydrochloric acid p rovided enantio- and diastereopure 5. Reaction of 1-phenyl-1-(trimethy lsiloxy)ethene with 1 afforded 8a and 8b in a ratio of 1:9. Deprotecti on of 8a, b and separation of the diastereomers give after diastereose lective reduction of the ketone function and conversion of the urethan e moiety into the methyl group natural (-)-hydroxysedamine (10). Start ing from 8b, deprotection and inversion of the OH function furnished 1 2 as a single homochiral diastereomer which was converted to ent-10.