Boc-L-Dmt-OH as a Fully N,S-Blocked Cysteine Derivative for Peptide Synthesis by Prior Thiol Capture. Facile Conversion of N-Terminal Boc-L-Dmt-Peptides to H-Cys(Scm)-Peptides

Article abstract of DOI:10.1021/jo00276a026

An efficient, convenient preparation of N-L-(tert-butyloxycarbonyl)-2,2-dimethylthiazolidine-4-carboxylic acid (Boc-Dmt-OH) is reported.The following rate constants assess the coupling efficiency and racemization risk of Boc-L-Dmt-OC6F5 in THF at 22 deg C.With H-Val-OMe, k_couple = 3.2*10^-2M^-1s^-1, and with Et3N, k_rac < 10^-8M^-1s^-1.Conversions of derivatives of the sequence Cys-Gly-Gly-Ala to the corresponding Scm-functionalized (Scm = methoxycarbonylsulfenyl, MeOCOS) cysteine peptides illustrated transformation of -Dmt- to -Cys(Scm)- with or without prior Boc cleavage.A palladium black catalyzed hydrogenolysis of a benzyl ester in the presence of the thiazolidine is reported in the solution-phase synthesis of the tripeptide Boc-Dmt-Leu-Ala-OBzl.The functionalized octapeptide 58-51 of basic pancreatic trypsin inhibitor, H-Cys(Scm)-Met-Arg-Thr-Cys(Dnp)-Gly-Gly-Ala-OH, was prepared by a 4 + 4 thiol capture and acyl-transfer strategy to demonstrate the applicability of the thiazolidine to this method.