Lipase-catalyzed two-step transesterification of diols: Estimation of selectivities

Reactions for the lipase-catalyzed kinetic resolution of chiral diols or the desymmetrization of achiral meso-diols involve two alternative routes, each of which contains two steps. During such reactions, up to four different nucleophiles compete to attack the acyl-enzyme intermediate of the catalyt...

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Bibliographic Details
Published in:	Biochemical engineering journal Vol. 195; p. 108911
Main Authors:	de Figueiredo, Tatiana Ziemniczak Pereira, Voll, Fernando Augusto Pedersen, Krieger, Nadia, Mitchell, David Alexander
Format:	Journal Article
Language:	English
Published:	Elsevier B.V 01-06-2023
Subjects:	Candida antarctica Lipase B (CALB) Lipozyme RM IM Specificity constants Two-step desymmetrization Two-step kinetic resolution Two-step kinetic resolution Candida antarctica Lipase B (CALB) Lipozyme RM IM Specificity constants Two-step desymmetrization
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Summary:	Reactions for the lipase-catalyzed kinetic resolution of chiral diols or the desymmetrization of achiral meso-diols involve two alternative routes, each of which contains two steps. During such reactions, up to four different nucleophiles compete to attack the acyl-enzyme intermediate of the catalytic cycle. The selectivities of the lipase for these different nucleophiles determines the success of the desymmetrization or resolution process and are important parameters for time-based mathematical models of these processes. Current methods for estimating these selectivities are not sufficiently accurate. In the current work, we develop a new approach to determining selectivities in lipase-catalyzed desymmetrization or resolution reactions with diols. The method is based on a model in which the only parameters are selectivities. We demonstrate the application of the method using literature data for three case studies of increasing complexity: (i) the two-step acetylation of phlorizin; (ii) the kinetic resolution of racemic 1,3-butanediol and (iii) the two-step desymmetrization of a meso-diol to produce a monoacetylated diol that is a key intermediate in the synthesis of biotin. We demonstrate the advantages of our estimation method over previously proposed estimation methods. The selectivities estimated by our method will be important parameters in models describing the desymmetrization and resolution of diols. [Display omitted] •Addresses two-step lipase-catalyzed desymmetrization or kinetic resolutions of diols.•Proposes new mathematical method for estimating selectivities in these systems.•Applies the new method to three case studies of increasing complexity.•Shows that the new method gives better estimates than previous methods.
ISSN:	1369-703X 1873-295X
DOI:	10.1016/j.bej.2023.108911