Key intermediates in the synthesis of enantiopure antagonists at NMDA receptors: a structural study

The two diastereomeric amino acid derivatives 8 (3a S ,5 R ,6a S )-5- tert -butoxycarbonylamino-4,5,6,6a-tetrahydro-3a H -cyclopenta[ d ]isoxazole-3,5-dicarboxylic acid diethyl ester, its epimer 9 (3a S ,5 S ,6a S ), and carboxylic acid 10 obtained by hydrolysis of 9 , which are intermediates in the synthesis of novel NMDA receptor antagonists 6 and 7 (Fig. 1), have been characterized by X-ray studies at 293 K for 8 and 10 , and at 100 K for 9 . The configuration of the carbon binding the 5- tert -butoxycarbonylamino moiety (BOC) determines the different molecular complexity: the chain structure for 8 , dimeric for 9 , and chain dimers for 10 . The pharmacophoric parameters in compound 8 (from which the active 7 is derived) are comparable with those observed for NMDA receptor antagonism, while 9 and 10 do not present the structural features, which match these pharmacophoric characteristics.