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Asymmetric Synthesis and Receptor Pharmacology of the Group II mGlu Receptor Ligand (1 S ,2 R ,3 R ,5 R ,6 S )‐2‐Amino‐3‐hydroxy‐bicyclo[3.1.0]hexane‐2,6‐dicarboxylic Acid—HYDIA
Author(s) -
Woltering Thomas J.,
Adam Geo,
Huguenin Philipp,
Wichmann Jürgen,
Kolczewski Sabine,
Gatti Silvia,
Bourson Anne,
Kew James N. C.,
Richards Grayson,
Kemp John A.,
Mutel Vincent,
Knoflach Frédéric
Publication year - 2008
Publication title -
chemmedchem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.817
H-Index - 100
eISSN - 1860-7187
pISSN - 1860-7179
DOI - 10.1002/cmdc.200700226
Subject(s) - bicyclic molecule , metabotropic glutamate receptor , stereochemistry , chemistry , agonist , ligand (biochemistry) , metabotropic receptor , receptor , biochemistry
The asymmetric synthesis and receptor pharmacology of (1S,2R,3R,5R,6S)‐2‐amino‐3‐Hydroxy‐bicyclo[3.1.0]hexane‐2,6‐dicarboxylic Acid (+)‐ 9 (HYDIA) and a few of its O‐alkylated derivatives are described. The key step of the synthesis utilizes Sharpless’ asymmetric dihydroxylation (AD‐β) for the kinetic resolution of a bicyclic racemic precursor olefin. In contrast to the bicyclic glutamate analogue LY354740, which is a potent and selective agonist for the group II metabotropic glutamate receptors (mGluRs), these new conformationally restricted and also hydroxylated or alkoxylated glutamate analogues are potent and selective antagonists for the group II mGluRs.