Peptide synthesis by prior thiol capture—V. The scope and control of disulfide interchange during the acyl transfer step

✍ Scribed by D.S. Kemp; Nader Fotouhi

• Book ID: 104227895
• Publisher: Elsevier Science
• Year: 1987
• Tongue: French
• Weight: 233 KB
• Volume: 28
• Category: Article
• ISSN: 0040-4039
• DOI: 10.1016/s0040-4039(00)96584-5

✦ Synopsis

Disulfide interchange in DMSO, during amide formation by prior thiol capture is reduced to less than 3% at low concentrations (<lo M) of substrate in the absence of air and light, and in the presence of 2.5 to 10 mole % AgNo3T The rate and selectivity of the exchange process were assessed by reacting 6 with a thiol; 7 was formed almost exclusively with a rate constant on the order of 10 to 10 M s .

As seen in Scheme I, the thiol capture strategy involves linkage of a pair of peptide fragments 1 and 2 with the unsymmetrical disulfide bond of 3, using the Scm group of Brois, .

Hiskey and Kamber.' Amide-forming intramolecular O,N-acyl transfer then occurs in the aminolysis-accelerating solvent DMSO. Since the key to the overall strategy is the use of a relatively unactivated phenyl ester 3 for the acyl transfer step, it was essential to define the degree to which disulfide interchange provides a competing series of side reactions during