Studies on amino acids and peptides VIII : Synthesis and crystal structure of two monothiated analogues of Boc-Gly-S-Ala-Aib-OMe

Abstract

The model tripeptide Boc-Gly-S-Ala-Aib-OMe ( 2b ) and the two monothiated analogues Boc-Gly( 1ψ 2CSNH)-S-Ala-Aib-OMe ( 2c ) and Boc-Gly-S-Ala( 2ψ 3 CSNH)-Aib-OMe ( 2a ) were synthesized. Peptide 2a was obtained by thiation of 1a using 2,4-bis(4-methoxyphenyl)-1,3,2,4-dithiadiphosphetane 2,4-disulfide, Lawesson's Reagent (LR), followed by deprotection of the Boc group and coupling with Boc-Gly-OH. Thiation of 2b with LR regiospecifically transformed the protected tripeptide to the monothiated analogue 2c . X-Ray diffraction analysis showed that the type-III β-turn formed by the reference peptide 2b is preserved in the monothiated analogue 2a ; conversely,the structure of the isomeric tripeptide 2c is partially extended.