The role of biocatalysis in the asymmetric synthesis of alkaloids

Schrittwieser, Joerg H.; Resch, Verena

doi:10.1039/c3ra42123f

Cited by 67 publications

(50 citation statements)

References 241 publications

(200 reference statements)

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“…Enzymes are very interesting [1][2][3][4][5][6][7] but they also have some limitations as industrial biocatalysts [8]. This occurs for example with the moderate stability of enzymes under conditions sometimes required by industry [9,10].…”

Section: Introductionmentioning

confidence: 98%

Immobilization of lipases on glyoxyl–octyl supports: Improved stability and reactivation strategies

Suescun

Rueda

Santos

et al. 2015

Process Biochemistry

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Section: Introductionmentioning

confidence: 98%

Immobilization of lipases on glyoxyl–octyl supports: Improved stability and reactivation strategies

Suescun

Rueda

Santos

et al. 2015

Process Biochemistry

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“…The blocking of the “normal” reaction center with a fluoro moiety achieved a complete switch in regioselectivity, leading to the formation of excellent yields (32–50 %) of the ( S )‐11‐hydroxy functionalized protoberberines and the remaining ( R )‐benzylisoquinolines. It was notable that notwithstanding the change in regioselectivity, the enantioselectivity of the products was fully conserved (>97 % ee ) and such strategies hold considerable promise for the generation of enantiomerically pure novel berberine and benzylisoquinoline derivatives, (Figure ).…”

Section: Berberine Bridge Enzyme (Bbe)mentioning

confidence: 99%

Biocatalyzed C−C Bond Formation for the Production of Alkaloids

2018

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Traditional methods of chemical synthesis of alkaloids exhibit various problems such as lack of enantioselectivity, the use of toxic chemical and intermediates, and multiple numbers of synthetic steps. Consequently, various enzymatic methods for the formation of CÀC bonds in the alkaloid skeleton have been developed. Herein, we report advances achieved in the enzymatic or chemo-enzymatic synthesis of pharmaceutically important alkaloids that employ three CÀC bond forming enzymes: two Pictet-Spenglerases and the oxidative CÀC bond forming flavoenzyme Berberine Bridge Enzyme. Protein engi-neering studies, improving the substrate scope of these enzymes, and thereby leading to the synthesis of non-natural alkaloids possessing higher or newer pharmacological activities, are also discussed. Furthermore, the integration of these biocatalysts with other enzymes, in multi-enzymatic cascades for the enantioselective synthesis of alkaloids, is also reviewed. Current results suggest that these enzymes hold great promise for the generation of CÀC bonds in the selective synthesis of alkaloid compounds possessing diverse pharmacological properties.

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“…D-Fagomine is a naturally occurring iminosugar which can be found in plants in small quantities. 19 The strategy devised in this work consisted of the simultaneous use of three enzymes: horse liver alcohol dehydrogenase (HLADH) used for the oxidation of N-Cbz-3-aminopropanol (1) to N-Cbz-3-aminopropanal (2), D-fructose-6-phosphate aldolase (FSA) variant A129S for the aldol addition, and a third enzyme; NADH oxidase (NOX) for coenzyme regeneration (Scheme 1). Lactobacillus).…”

Section: Introductionmentioning

confidence: 99%

A new concept for production of (3S,4R)-6-[(benzyloxycarbonyl)amino]-5,6-dideoxyhex-2-ulose, a precursor of d-fagomine

et al. 2015

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A novel cascade reaction for the production of aldol adduct (3S,4R)-6-[(benzyloxycarbonyl)amino]-5,6dideoxyhex-2-ulose was studied in this work. The strategy combines three enzymes in one pot: (i) horse liver alcohol dehydrogenase for the oxidation of N-Cbz-3-aminopropanol to the corresponding aldehyde, (ii) NADH oxidase for the regeneration of coenzyme NAD + and (iii) D-fructose-6-phosphate aldolase from E. coli A129S variant for the aldol addition of dihydroxyacetone to N-Cbz-3aminopropanal. On the basis of preliminary experiments, optimization of the initial reaction conditions was done using statistical methods, i.e. factorial design of experiments. 79% yield of aldol adduct was achieved in the batch reactor after optimization.Scheme 1 Reaction scheme of cascade reaction of amino alcohol 1 oxidation to 2 with coenzyme regeneration using NOX and aldol addition of DHA to 2 catalyzed by FSA A129S. 69820 | RSC Adv., 2015, 5, 69819-69828This journal is

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The role of biocatalysis in the asymmetric synthesis of alkaloids

Abstract: This article reviews the progress in chemo-enzymatic alkaloid synthesis over the last 25 years, focusing on recent developments that have led to significant improvements in terms of step-economy and yield.

Cited by 67 publications

References 241 publications

Immobilization of lipases on glyoxyl–octyl supports: Improved stability and reactivation strategies

Immobilization of lipases on glyoxyl–octyl supports: Improved stability and reactivation strategies

Biocatalyzed C−C Bond Formation for the Production of Alkaloids

A new concept for production of (3S,4R)-6-[(benzyloxycarbonyl)amino]-5,6-dideoxyhex-2-ulose, a precursor of d-fagomine

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