I want to form a thioester between some acyl chlorides and NBoc-cysteine. Is the free thiol so much more reactive than the carboxylic acid in cysteine that the side product formation of carboxylic anhydrides is negligible?


1 Answer 1


I think so that's the case according to Ref.1. For example:

S-acylation of ceisteine

Your $\ce{R^1}$-group can be one you wish to have. A typical procedure to prepare S-Acylation of N-protected-cysteines is given in the reference as follows:

To a solution of N-protected-L-cysteine ($\bf{4a-c}$; $\pu{1 mmol}$) in THF ($\pu{5 mL}$) was added a solution of acyl 1-benzotriazolyl $\bf{5}$ ($\pu{1 mmol}$) in THF ($\pu{5 mL}$) in the presence of $\ce{KHCO3}$ ($\pu{1 mmol}$). The heterogeneous mixture was then stirred at room temperature for $\pu{12 h}$. THF was evaporated, and the solution was acidified with $\ce{HCl}$, and the solid formed was taken in ethyl acetate and washed with $\ce{HCl}$ ($\pu{1N}$, 3×) and brine (3×) and then dried over sodium sulfate. Evaporation of ethyl acetate under reduced pressure afforded N-protected S-acyl cysteine.


  1. Tarek S. Ibrahim, Srinivasa R. Tala, Said A. El-Feky, Zakaria K. Abdel-Samii, and Alan R. Katritzky, "Cysteinoyl- and Cysteine-containing Dipeptidoylbenzotriazoles with Free Sulfhydryl Groups: Easy Access to N-terminal and Internal Cysteine Peptides," Chemical Biology & Drug Design 2012, 80(2), 194-202 (DOI: https://doi.org/10.1111/j.1747-0285.2011.01303.x).

Your Answer

By clicking “Post Your Answer”, you agree to our terms of service and acknowledge you have read our privacy policy.

Not the answer you're looking for? Browse other questions tagged or ask your own question.