C O M M U N I C A T I O N S
and cysteine (10 equiv). As shown in Scheme 6, we confirmed the
formation of N-acylcysteine 7, benzamide (9), and cystine (11) in
high yields. On the basis of the products observed, we propose the
following mechanism: The reaction is initiated by reversible thiol
exchange between 5a and cysteine to first generate the new thioester
6 and N-mercaptobenzamide (8). Compound 6 then undergoes fast
S-to-N acyl transfer to form amide 7. This process is similar to the
well-known NCL reaction. Meanwhile, the reaction between 8 and
excess cysteine should lead to 9 and cysteine perthiol (10). Finally,
the reaction between 10 and cysteine should complete the generation
of H2S and provide 11.
together with the donor in order to produce H2S, which may
compromise the redox balance of the system under study. Therefore,
careful control experiments are needed in order to clarify the
potential problem. Nevertheless, N-(benzoylthio)benzamides provide
researchers with new H2S donor options, and we expect them to
be useful tools in H2S studies. Further development of N-mercapto-
based H2S donors and evaluation of their biological activities are
currently ongoing in our laboratory.
Acknowledgment. This work was supported in part by NIH
(R01GM088226) and a CAREER Award from NSF (0844931). We
thank Prof. Jack R. Lancaster, Jr. (University of Alabama) and Prof.
David J. Lefer (Emory University) for help discussion.
Scheme 6. Proposed Mechanism of H2S Generation
Supporting Information Available: Spectroscopic and analytical
data and selected experimental procedures. This material is available
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