Synthesis of 6,6-pentamethylene-2-aminosuberic acid. A key intermediate in the synthesis of dicarba analogs of vasopressin antagonists

• Published in: Journal of organic chemistry Vol. 53; no. 7; pp. 1527 - 1530
• Main Authors: Callahan, James F, Newlander, Kenneth A, Bryan, Heidemarie G, Huffman, William F, Moore, Michael L, Yim, Nelson C. F
• Format: Journal Article
• Language: English
• Published: WASHINGTON American Chemical Society 01.04.1988; Amer Chemical Soc
• Subjects: Alicyclic compounds; Alicyclic compounds, terpenoids, prostaglandins, steroids; Chemistry; Chemistry, Organic; Exact sciences and technology; Organic chemistry; Physical Sciences; Preparations and properties; Science & Technology; Aliphatic compound; Aminoacid; Saturated compound; Dicarboxylic acid; Optical purity; Stereospecificity; Antagonist; Kolbe electrosynthesis; Electrochemical reaction; Monocyclic compound; Vasopressin
• ISSN: 0022-3263; 1520-6904
• 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(OBz)-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.