As part of a program aimed at the design of conformationally constrained analogs of glutamic acid, (+)-2-aminobicyclo[3.1.0]hexane-2,6-carboxylic acid (1), identified as a highly potent, selective, group II metabotropic glutamate receptor agonist has been synthesized and studied clinically. Heterocyclic analogs of 1 were subsequently synthesized in which the C-2 methylene has been replaced by an oxygen atom (2) or a sulfur atom (3). C-14 labeled isotopomers of 1, 2 and 3 have been synthesized to facilitate pre-clinical ADME studies. A tritium labeled isotopomer of 1 was also synthesized for use in in vitro experiments. A stable labeled isotopomer of rac-1 was prepared for use as an internal standard for bioanalytical assays. The key step in each of these syntheses was the reaction of chiral ketone 4, 5 or 6 with K 14 CN/(NH 4 ) 2 CO 3 using the Bucherer-Berg protocol. In the preparation of the stable labeled isotopomer, rac-4-[ 13 C 2 ] was prepared in two steps from ethyl bromoacetate-[UL-13 C 2 ]; subsequent reaction of rac-4-[ 13 C 2 ] with K 13 CN/ 15 NH 4 Cl/Na 2 CO 3 , followed by hydrolysis of the hydantoin yielded rac-1-[ 13 C 3 , 15 N].