3. Msbh, a Safety Catch Cysteine Protecting Group for the Synthesis of Cyclic Peptides

References: f Direct palladium-mediated on-resin disulfide formation from Allocam protected peptides; T. D. Kondasinghe, H. Y. Saraha, S. B. Odeesho and J. L. Stockdill; Org Biomol Chem 2017; 15: 2914-2918. doi:10.1039/c7ob00536a f Disulfide Formation Strategies in Peptide Synthesis; T. M. Postma and F. Albericio; European Journal of Organic Chemistry 2014; 2014: 3519-3530. doi:10.1002/ejoc.201402149

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Enhanced microwave-assisted method for on-bead disulfide bond formation: synthesis of alpha-conotoxin MII; A. S. Galanis, F. Albericio and M. Grotli; Peptide Science 2009; 92: 23-34. doi:10.1002/bip.21116

Allylic protection of thiols and cysteine: I: The allyloxycarbonylaminomethyl group; A. Malanda Kimbonguila, A. Merzouk, F. Guibé and A. Loffet; Tetrahedron 1999; 55: 6931-6944. doi:10.1016/s0040-4020(99)00322-1

Allylic protecting groups and their use in a complex environment part II: Allylic protecting groups and their removal through catalytic palladium π-allyl methodology; F. Guibé; Tetrahedron 1998; 54: 2967-3042. doi:10.1016/s0040-4020(97)10383-0

Use of Alloc-amino acids in solid-phase peptide synthesis. Tandem deprotection-coupling reactions using neutral conditions; N. Thieriet, J. Alsina, E. Giralt, F. Guibé and F. Albericio; Tetrahedron Letters 1997; 38: 7275-7278. doi:10.1016/s0040-4039(97)01690-0

The allyloxycarbonylaminomethyl group: a new allytic protection for the thiol group of cysteine; A. M. Kimbonguila, A. Merzouk, F. Guibé and A. Loffet; Tetrahedron Letters 1994; 35: 9035-9038. doi:10.1016/0040- 4039(94)88420-x

The regioselective formation of S-S-bonds presents the greatest synthetic challenge in the preparation of disulfide-bridged peptides, especially when multiple cysteine residues are present. In these cases, orthogonal Cys protecting groups are

Cleavage of the Msbh Cysteine Protecting Group

The innovative Msbh protecting group is stable to the deprotection conditions of most common cystein PGs such as Mmt (monomethoxytrityl), Trt (trityl), Acm (acetylaminomethyl) or Phacm (phenylacetylaminomethyl). Moreover, it is stable to conditions applied in both Boc and Fmoc chemistry. Reduction of the sulfoxide to the sulfide renders the bond between the cysteine sulfhydryl group and the benzylic carbon of the Msbh group acid labile, and thus enables facile deprotection using TFA.