Synthesis of GABA-analogous spirocyclic amino acids, 4. N-benzyl-2-azaspiro[4.4]nonane-6-carboxylates

Alkylation of 2-oxocyclopentanecarboxylate (4) with 1,2-dibromoethane and reaction with benzyl-amine gave 2-azaspiro[4. 4]nonane-1, 6-dione (7). After selective reduction of 7 at the lactam function, we obtained 2-azaspiro [4. 4]nonan-6-one (9) which was treated with TosMIC/tert-BuOK to yield a mixture of diastereomeric nitriles (11a) and (11b). Hydrolysis followed by esterification and mplc separation led to diastereomerically pure esters (3a) and (3b) which represent novel analogs of GABA with restricted conormational flexibility.