New view of acylase promiscuity: An extended study on the acylase-catalyzed Markovnikov addition

Acylases have shown several promiscuities towards non-natural substrates. For example, acylases have been proved to be able to catalyze Markovnikov addition of N-heterocycles to vinyl esters recently. Some interesting and unexplainable observations drew our attention, and the acylase-catalyzed Markovnikov addition was investigated further in this paper. We detected an acylation product in the reaction and found that acetaldehyde was able to improve the reaction rate. Moreover, Markovnikov adduct could be formed using isopropenyl acetate or 2,2,2-trifluoro-ethyl acetate as substrates in the presence of acetaldehyde. Based on these results, it was proposed that the so-called acylase-catalyzed Markovnikov addition actually consisted of three steps identified as acylation, hemiaminal intermediate formation and transesterification. This discovery revealed that the promiscuity of acylase for Markovnikov addition was pseudo-promiscuity.

Acylase-catalyzed Markovnikov addition was elucidated as the reaction consisted of three processes identified as acylation, hemiaminal intermediate formation and transesterification.Figure optionsDownload as PowerPoint slideHighlights
► Extended study is performed to understand the acylase-catalyzed Markovnikov addition.
► We find that acylase-catalyzed Markovnikov addition consisted of three processes.
► This discovery reveals that acylase promiscuity for Markovnikov addition was pseudo-promiscuity.