Enzymatic Synthesis of Thioesters from Thiols and Vinyl Esters in a Continuous-Flow Microreactor

Abstract

The preparation of thioesters through the lipase-catalysed transesterification reaction of thiols with vinyl carboxyl esters is described. The reactions were carried out by Lipase TL IM from Thermomyces lanuginosus as a catalyst and performed under a continuous flow microreactor. We first found that lipase TL IM can be used in the reaction of thioester synthesis with high efficiency. Various reaction parameters were investigated including substrate molar ratio, reaction time, and temperature. Maximum conversion (96%) was obtained under the optimal condition of a substrate molar ratio of 1:2 (4-methylbenzyl mercaptan:vinyl esters) at 50 • C for about 30 min. Compared with other methods, the salient features of this work include mild reaction conditions (50 • C), short reaction times (30 min), high yields, and environment-friendliness.

Eat1-Like Alcohol Acyl Transferases From Yeasts Have High Alcoholysis and Thiolysis Activity

“…Finally, we discovered that Eat1 also shows thiolysis activity. Thiolysis is known to be catalyzed by lipases from R. miehei (Lipozyme IM 20 R ), C. antarctica (Novozym 435 R ), or Thermomyces lanuginosus for the production of thiobutyl butyrate, thiobutyl valerate, thiostearyl palmitate, thiohexyl octanoate and other acetate thioesters (Zaks and Klibanov, 1985;Cavaille-Lefebvre and Combes, 1997;Weber et al, 1999;Hedfors et al, 2010;Zhou et al, 2018). To our knowledge, this is the first time that an esterase was shown to catalyze thiolysis of short chain thioesters.…”

Microbial Lipases and Their Potential in the Production of Pharmaceutical Building Blocks

“…The attractiveness of microbial lipases in applications also lies in their versatility, by facilitating the transfer of acyl groups from a wide number of substrates, not only to water (its natural substrate), but also to various nucleophiles such as H 2 O 2 [ 19 ], alcohols (including derivatives like sugars) [ 20 ]), amines [ 21 ], amino acids [ 22 ], amino alcohols [ 23 ] and thiols [ 24 ], among others, which results in a wide potential for application in organic synthesis reactions as those involved in the production of building blocks of Active Pharmaceutical Ingredients (APIs). To thermodynamically favor synthesis over hydrolysis reactions, it is necessary that the reaction media maintain, among other characteristics, a low aqueous activity (a w ).…”

A strategic Ser/Cys exchange in the catalytic triad unlocks an acyltransferase-mediated synthesis of thioesters and tertiary amides

“…The mutant, tolerating high substrate loading and working without the addition of cofactors, makes the process very attractive and efficient in terms of STY and TON (5-6 x 10 3 ) which, for thioester synthesis, is four orders of magnitude higher than the mentioned enzymatic examples. 11 The WT used as a control, never showed activity towards thiols and secondary amines even at high catalyst concentrations. Acetyl-CoA and its analogues were prepared with excellent conversions (80->99%), and very good reaction times.…”

“…9 TL IM lipase from Thermomyces lanuginosus and D-amino acylase from E. coli have been applied for the preparation of thioesters in organic solvent, but low space time yields (STY), turnover number (TON) and limited substrate range were observed despite the use of high amount of catalyst. 10,11 Similarly, Candida antarctica lipase B (CALB) was employed to prepare an intermediate tertiary amide towards the synthesis of alfuzosin, but again with an extremely poor catalyst-to-substrate ratio. 12 While the enzymatic synthesis of secondary amides counts many examples, 4 that of tertiary amides is rarely observed.…”