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Synthesis and n methyl d aspartate nmda antagonist properties of the enantiomers of alpha amino 5 phosphonomethyl 1 1' biphenyl 3 propanoic acid use of a new chiral glycine derivative



Synthesis and n methyl d aspartate nmda antagonist properties of the enantiomers of alpha amino 5 phosphonomethyl 1 1' biphenyl 3 propanoic acid use of a new chiral glycine derivative



Helvetica Chimica Acta 75(3): 855-864



The enantiomers of the title compound, 7a and ent-7a, and of substituted analogues are synthesized. The absolute configuration of 7a is deduced from that of (tert-butyl 2-tert-butyl)-3-methyl-4-oxoimidazolidin-1-carboxylate (15) and from the trans-configuration of the intermediate 17a which in turn is assigned on the basis of 1H-NMR nuclear Overhauser effect (NOE) measurements. Instead of 15, the 2-isopropyl-substituted analogue 21 can also be employed. Its preparation from glycine, methylamine, isobutyraldehyde, and (Boc)2O, and the resolution through the bis-O,O'-(4-toluyl)tartrate salt 20 are described. In two functional tests (rat neocortical slice and frog hemisected spinal cord preparation) the (S)-enantiomer 7a (SDZ EAB 515) is shown to be a very potent, selective competitive NMDA antagonist.

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