GABA-analogous spirocyclic amino acid esters, 5. N-benzyl-7-azaspiro[4.5]decane-1-carboxylates

N-Benzyl-7-azaspiro[4.5]decane-1-carboxylates (4a and 4b) were prepared in a seven step synthesis starting from ethyl cyclopentanonecarboxylate (5). A minolysis of the beta-keto ester (5) with benzylamine led to the beta-keto amide (9) which gave the alpha-substituted beta-keto amide (10) by addition of acrolein. Reduction of 10 with LiAlH4 resulted in a reductive cyclizati on yielding a mixture of the epimeric spirocyclic alcohols (12a and 12b, 3: 1). Oxidation of the alcohols (12a and 12b) was archieved with (COCl)(2)/DM SO giving the spirocyclic ketone (14). Treatment of 14 with tosylmethyl iso cyanide and tert-BuOK yielded a mixture of diastereomeric nitriles (15a and 15b, 6:4) which was separated by chromatography. Hydrolysis and esterifica tion of 15a and 15b led to the diastereomerically pure amino acid eaters (4 a and 4b) which represent novel analogs of GABA with restricted conformatio nal flexibility.