Synthesis of 6,6-Pentamethylene-2-aminosuberic Acid. A Key Intermediate in the Synthesis of Dicarba Analogues of Vasopressin Antagonists

Article abstract of DOI:10.1021/jo00242a035

Two complementary syntheses of the unnatural amino acid, 6,6-cyclopentamethylene-2-aminosuberic acid, Pas (2) are described.The first, starting from methyl cyclohexanecarboxylate (4), yields in ten steps racemic Boc-Pas(OBzl)-OH (3) which is suitably protected for solid phase peptide synthesis.The second method involves the stereospecific synthesis of optically pure Boc-Pas(OBzl)-OH (3L) utilizing the electrochemical coupling, via the Kolbe method of the monobenzyl ester of 1,1-cyclohexanediacetic acid (13) and Boc-L-Glu-OBzl (14).The optical purity of 3L was confirmed by chiral gas chromatographic analysis of its N-pentafluoropropionyl diisopropyl ester derivative 15L.