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Novel Approach to the (–)‐Sparteine‐Mediated Synthesis of Kainoids:Total Synthesis of (–)‐α‐Kainic Acid by (–)‐Sparteine‐Mediated Deprotonation
Author(s) -
Montserrat Martínez M.,
Hoppe Dieter
Publication year - 2005
Publication title -
european journal of organic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.825
H-Index - 155
eISSN - 1099-0690
pISSN - 1434-193X
DOI - 10.1002/ejoc.200400824
Subject(s) - chemistry , sparteine , kainic acid , deprotonation , stereochemistry , pyrrolidine , stereospecificity , intramolecular force , carbamate , medicinal chemistry , organic chemistry , catalysis , glutamate receptor , biochemistry , ion , receptor
We report a new synthesis of kainoids via allyllithium compounds using an intramolecular cycloalkylation as the key step. Preparation of different substituted pyrrolidines was carried out by using carbamates, that react with the chiral base n ‐BuLi/(–)‐sparteine with strong selection between the diastereotopic protons adjacent to the carbamate group in favour for the pro‐S proton. (–)‐α‐Kainic acid was synthetized from D ‐serine methyl ester hydrochloride, based on a (–)‐sparteine‐mediated asymmetric deprotonation of an intermediate carbamate that, by stereospecific anti ‐S N ′S E ′ intramolecular cycloalkylation, leads to the pyrrolidine ring precursor of (–)‐α‐kainic acid, in high yield and diastereoselectivity. Related approaches, starting from L ‐glutamic acid failed. The intermediate pyrrolidine was further transformed to (–)‐α‐kainic in three steps. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2005)