3-Carboxy-4-phosphonocyclopentane amino acids: New metabotropic glutamate receptor ligands

Summary.

 Two glutamic acid analogs (1SR,3RS,4RS)- and (1SR,3SR,4SR)-1-amino-4-phosphono cyclopentane-1,3-dicarboxylic acids (APCPD) have been synthesized. Pure E-(diethoxy-phosphoryl)-acrylic acid ethyl ester was obtained from ethyl propiolate, phenol and triethylphosphite. It was used as dienophile in a Diels-Alder reaction. Oxidation and cyclization afforded 3-(ethoxy-carbonyl)-4-(diethoxy-phosphoryl)-cyclopentanone. Bucherer-Bergs reaction and hydrolysis yielded APCPD-III and -IV which are inactive on mGlu1a receptor and antagonists on mGlu2 and mGlu8a receptors.