Lipase-Mediated Kinetic Resolution: An Introductory Approach to Practical Biocatalysis

Bandeira, Pamela T.; Thomas, Juliana Christina; Oliveira, Alfredo R. M. de; Piovan, Leandro

doi:10.1021/acs.jchemed.6b00606

Cited by 6 publications

(5 citation statements)

References 27 publications

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“…Hence, the synthesis of chiral molecules has drawn immense attention from the pharmaceutical industry as well as of drug regulatory authorities (FDAs). The well-established method for the production of enantiomerically enriched alcohols is their enzyme-catalyzed acylation or hydrolysis of their racemic esters . To endorse our new protocol for the synthesis of the nonracemic alcohols, we first studied the enzymatic kinetic resolution (KR) of racemic 1-phenylethanol rac -( 4a ) as a model substrate.…”

Section: Resultsmentioning

confidence: 96%

Evaluation of gem-Diacetates as Alternative Reagents for Enzymatic Regio- and Stereoselective Acylation of Alcohols

et al. 2021

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Geminal diacetates have been used as sustainable acyl donors for enzymatic acylation of chiral and nonchiral alcohols. Especially, it was revealed that geminal diacetates showed higher reactivity than vinyl acetate for hydrolases that are sensitive to acetaldehyde. Under optimized conditions for enzymatic acylation, several synthetically relevant saturated and unsaturated acetates of various primary alcohols were obtained in very high yields up to 98% without E/Z isomerization of the double bond. Subsequently, the acyl donor was recreated from the resulting aldehyde and reused constantly in acylation. Therefore, the developed process is characterized by high atomic efficiency. Moreover, it was shown that acylation using geminal diacetates resulted in remarkable regioselectivity by discriminating among the primary and secondary hydroxyl groups in 1-phenyl-1,3-propanediol providing exclusively 3-acetoxy-1-phenyl-propan-1-ol in good yield. Further, enzymatic kinetic resolution (EKR) and chemoenzymatic dynamic kinetic resolution (DKR) protocols were developed using geminal diacetate as an acylating agent, resulting in chiral acetates in high yields up to 94% with enantiomeric excesses exceeding 99%.

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Section: Resultsmentioning

confidence: 96%

Evaluation of gem-Diacetates as Alternative Reagents for Enzymatic Regio- and Stereoselective Acylation of Alcohols

et al. 2021

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“…18 After some experimentation which involved screening some solvents and amount of CALB, we found that by using a toluene/MTBE mixture (8:2, V/V) and increasing the amount of CALB to a 2:1 mass ratio compared to the substrate, treatment of benzylic alcohol (+/-)-6 with vinyl acetate provided the corresponding enantiomerically pure acetate (S,S)-12 (30% yield) and enantiomerically pure alcohol (R,R)-6 (36% yield, >99% enantiomeric purity as determined by chiral HPLC, see SI). 19,20 Scheme 3. Enzymatic resolution of benzylic alcohol (+/-)-6.…”

Section: Scheme 1 Retrosynthetic Analysis Of Raputindole a (1)mentioning

confidence: 99%

Diastereoselective Total Synthesis of (+)-Raputindole A: An Iridium- Catalyzed Cyclization Approach

Pilli

Regueira²,

Silva³

2020

Preprint

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This work describes the total synthesis of Raputindole A <b>(1)</b> through a convergent approach which features: 1) an iridium-catalyzed cyclization to assembly the tricyclic core of the northern part, 2) enzymatic resolution to secure the preparation of enantiomerically pure benzylic alcohol, 3) installation of the butenyl substituent via methallylation of the corresponding benzylic carbocation and coupling of the northern and southern parts via Heck reaction. (+)-Raputindole A <b>(1)</b> was prepared in 10 steps (LLS) and 10% overall yield.

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“…If the enzyme is attached to a nonporous material, mass transfer limitations occur only because of the stagnant film, or Nernst layer surrounding the support material. Should the enzyme be entrapped inside a porous matrix, internal mass transfer limitations come into play as well. , Numerous experiments on enzyme catalysis have already been published in this Journal , focusing on fundamental and applied aspects of biocatalysis. − While immobilization has been tackled in diverse reports, − to the best of our knowledge no previous pedagogical experiment exists pertaining to the evaluation of immobilization on (observed) enzyme kinetics and substrate mass transfer.…”

Section: Introductionmentioning

confidence: 99%

Simple Protocol to Facilitate Students’ Understanding of the Effects of Enzyme Immobilization on Kinetics of Reaction and Mass Transfer

Simões

Malcata

2020

J. Chem. Educ.

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A laboratory experiment is described in which students carry out immobilization of the enzyme invertase via entrapment in alginate (Ca-alginate) and, accordingly, estimate values for kinetic constants and mass transfer coefficients. Immobilization of enzymes, or confinement thereof to a defined space with retention of most catalytic activity, is attractive for allowing repeated (and continuous) use. However, interest in immobilization hinges critically on whether and how it affects kinetic performance. The overall goal is indeed to retain as much activity as possible and minimize alteration of selectivity, while extending its useful life for as long as feasible. Toward this goal, it is relevant to quantify the effects of immobilization upon enzyme kinetics and mass transfer in particularwith the latter constraining observed (rather than intrinsic) reaction kinetics, owing to diffusional resistance. Invertase was selected as a model enzyme since the associated laboratory handling is safe, fast, reproducible, not expensive, and prone to easily attain the intended learning outcomes.

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Lipase-Mediated Kinetic Resolution: An Introductory Approach to Practical Biocatalysis

Cited by 6 publications

References 27 publications

Evaluation of gem-Diacetates as Alternative Reagents for Enzymatic Regio- and Stereoselective Acylation of Alcohols

Evaluation of gem-Diacetates as Alternative Reagents for Enzymatic Regio- and Stereoselective Acylation of Alcohols

Diastereoselective Total Synthesis of (+)-Raputindole A: An Iridium- Catalyzed Cyclization Approach

Simple Protocol to Facilitate Students’ Understanding of the Effects of Enzyme Immobilization on Kinetics of Reaction and Mass Transfer

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