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Synthesis of (+)‐ and (−)‐hydroxysedamine and (+)‐ N ‐methylpseudoconhydrine from ( S )‐glutamic acid via homochiral acyliminium ion
Author(s) -
Herdeis Claus,
Held Walter A.,
Kirfel Armin,
Schwabenländer Franz
Publication year - 1995
Publication title -
liebigs annalen
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.825
H-Index - 155
eISSN - 1099-0690
pISSN - 0947-3440
DOI - 10.1002/jlac.1995199507172
Subject(s) - chemistry , diastereomer , moiety , ketone , hydrochloric acid , yield (engineering) , stereochemistry , carboxylate , medicinal chemistry , organic chemistry , materials science , metallurgy
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 .