STUDIES ON AMINO ACIDS AND PEPTIDES XII. SYNTHESIS OF THIATED ANALOGUES OF Boc-S-Ala-Aib-S-Ala-OMe AND Ac-S-Ala-Aib-S-Ala-OMe

Article abstract of DOI:10.1016/S0040-4020(01)88119-9

The two model peptides Boc-S-Ala-Aib-S-Ala-OMe (1a) and Ac-S-Ala-Aib-S-Ala-OMe (1b) and their monothiated analogues Boc-S(R)-AlaΨ(CSNH)-Aib-S-Ala-OMe (3a), Boc-S-Ala-AibΨ(CSNH)-S-Ala-OMe (4a), AcΨ(CSNH)-S-Ala-Aib-S-Ala-OMe (2b), Ac-S-Ala-AibΨ(CSNH)-S-Ala-OMe (4b), and the dithiated Boc-S-AlaΨ(CSNH)-AibΨ(CSNH)-S-Ala-OMe (5a) are synthesized.Peptide 3a was obtained from the coupling of HCl*H-S-Ala-OMe to S-2-(1-tert-butoxycarbonylamino)ethyl-4,4-dimethyl-1,3-thiazol-5(4H)-one (11).The thioamide analogues 4a (together with 5a) and 2b were obtained by regioselective thiation of the respective model peptides 1a and 1b using 2,4-bis(4-methylphenyl)-1,3,2,4-dithiadiphosphetane 2,4-disulfide, Lawesson's Reagent (LR).Deprotection of the Boc group of 4a, followed by acetylation of the product, afforded 4b.The magnetic nonequivalence of the gem-methyl groups of Aib is discussed.