Synthesis of (+)- and (−)-hydroxysedamine and (+)-N-methylpseudoconhydrine from (S)-glutamic acid via homochiral acyliminium ion

✍ Scribed by Herdeis, Claus ;Held, Walter A. ;Kirfel, Armin ;Schwabenländer, Franz

• Publisher: John Wiley and Sons
• Year: 1995
• Tongue: English
• Weight: 749 KB
• Volume: 1995
• Category: Article
• ISSN: 0947-3440
• DOI: 10.1002/jlac.1995199507172

✦ Synopsis

Abstract

Efficient syntheses of (+)‐N‐methylpseudoconhydrine (5) and (−)‐hydroxysedamine (10) are described starting from the readily available (2__RS,5S__)‐Methyl 5‐(tert‐butyldimethyl‐silyloxy)‐2‐ethoxypiperidine‐1‐carboxylate (1) and proceeding via homochiral acyliminium ion as an intermediate. Compounds 5 and 7b were obtained in 32 and 34%, resp., overall yield from 1. After deprotection of the OH function of 3a, b the diastereomeric mixture of 6a, b was separated and converted to pseudoconhydrine 7b and epi‐pseudoconhydrine 7a, respectively. Reduction of the urethane moiety of 3a, b followed by treatment with hydrochloric acid provided enantio‐ and diastereopure 5. Reaction of 1‐phenyl‐1‐(trimethylsiloxy)ethene with 1 afforded 8a and 8b in a ratio of 1:9. Deprotection of 8a, b and separation of the diastereomers give after diastereoselective reduction of the ketone function and conversion of the urethane moiety into the methyl group natural (−)‐hydroxysedamine (10). Starting from 8b, deprotection and inversion of the OH function furnished 12 as a single homochiral diastereomer which was converted to ent‐10.