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Theoretical study on formation of thioesters via O-to-S acyl transfer

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  • Special Topic Physical Organic Chemistry in China
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Abstract

Peptide thioester preparation via intramolecular O-to-S acyl transfer is a recently developed method for protein chemical synthesis through Fmoc chemistry. Theoretical calculations have been carried out to study the mechanism for the formation of thioesters via O-to-S acyl transfer. It is found that the O-to-S acyl transfer occurs via an anionic stepwise mechanism in which the cleavage of the C-O bond is the rate-limiting step. The side reaction of hydrolysis also proceeds through an anionic stepwise process, and its rate-limiting step is the attack of the hydroxide ion on the carbonyl carbon. Increase of the chain length between the ester O atom and the S atom can increase the energy barrier of the O-to-S acyl transfer. On the other hand, substituents at the α-position of the ester can reduce the energy barrier.

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Authors and Affiliations

  1. College of Chemistry & Chemical Engineering, Shaoxing University, Shaoxing, 312000, China

    Chen Wang & Qing-Xiang Guo

  2. Department of Chemistry, University of Science and Technology of China, Hefei, 230026, China

    Chen Wang & Qing-Xiang Guo

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  1. Chen Wang
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  2. Qing-Xiang Guo
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Correspondence to Qing-Xiang Guo.

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Wang, C., Guo, QX. Theoretical study on formation of thioesters via O-to-S acyl transfer. Sci. China Chem. 55, 2075–2080 (2012). https://doi.org/10.1007/s11426-012-4711-x

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  • DOI: https://doi.org/10.1007/s11426-012-4711-x

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