Various aryl and alkyl substituted optically pure propargyl alcohols were obtained with excellent ee (up to >99%) and isolated yields (up to 87%) by deracemization using whole cells of Candida parapsilosis ATCC 7330. The whole cells show substrate specificity towards alkyl substituted propargyl alcohols and a switch in the enantioselectivity has been observed from 'R' to 'S' upon increasing the chain length. For the first time, enantiopure (R)-4-(3-hydroxybut-1-ynyl)benzonitrile, (R)-4-(biphenyl-4-yl)but-3-yn-2-ol, (S)-ethyl 3-hydroxy-5-phenylpent-4-ynoate and (S)-4-phenylbut-3-yne-1,2-diol were obtained using this strategy. Optically pure propargyl alcohol thus obtained was used as a chiral starting material in the synthesis of enantiomerically enriched poly-substituted pyrrolidines and a pyrrole derivative successfully demonstrating a chemoenzymatic route. This journal is © 2014 the Partner Organisations.

Anju Chadha

Department Of Biotechnology

Sushital Jana

Aromatic compounds

CANDIDA PARAPSILOSIS

CHEMO-ENZYMATIC SYNTHESIS

CHEMOENZYMATIC ROUTE

DE-RACEMIZATION

Isolated yield

Propargyl alcohol

PYRROLE DERIVATIVES

Substrate Specificity

Enantiomers

alkyne

polycyclic hydrocarbon

Propanol

pyrrolidine derivative

Biocatalysis

Candida

chemistry

conformation

Cytology

enzymology

high performance liquid chromatography

Organic Chemistry

procedures

Stereoisomerism

synthesis

X ray crystallography

Alkynes

Chemistry, Organic

Chromatography, High Pressure Liquid

Crystallography, X-Ray

Molecular Conformation

Polycyclic Compounds

PROPANOLS

Pyrrolidines

IIT Madras is a public technical and research university located in Chennai, Tamil Nadu. Founded in 1959, it is recognised as an Institute of National Importance.

IIT Madras has been ranked as the top engineering institute in India for four years in a row by the National Institutional Ranking Framework of the MHRD

It currently offers undergraduate, postgraduate and research degrees across 16 disciplines in Engineering, Sciences, Humanities and Management. About 596 faculty belonging to science and engineering departments and centres of the Institute are engaged in teaching, research and industrial consultancy.

IIT Madras

Organic and Biomolecular Chemistry

This review highlights the importance of the biocatalyst, Candida parapsilosis for oxidation and reduction reactions of organic compounds and establishes its versatility to generate a variety of chiral synthons. Appropriately designed reactions using C. parapsilosis effect efficient catalysis of organic transformations such as deracemization, enantioselective reduction of prochiral ketones, imines, and kinetic resolution of racemic alcohols via selective oxidation. This review includes the details of these biotransformations, catalyzed by whole cells (wild type and recombinant strains), purified enzymes (oxidoreductases) and immobilized whole cells of C. parapsilosis. The review presents a bioorganic perspective as it discusses the chemo, regio and stereoselectivity of the biocatalyst along with the structure of the substrates and optical purity of the products. Fermentation scale biocatalysis using whole cells of C. parapsilosis for several biotransformations to synthesize important chiral synthons/industrial chemicals is included. A comparison of C. parapsilosis with other whole cell biocatalysts for biocatalytic deracemization and asymmetric reduction of carbonyl and imine groups in the synthesis of a variety of enantiopure products is presented which will provide a basis for the choice of a biocatalyst for a desired organic transformation. Thus, a wholesome perspective on the present status of C. parapsilosis mediated organic transformations and design of new reactions which can be considered for large scale operations is provided. Taken together, C. parapsilosis can now be considered a ‘reagent’ for the organic transformations discussed here. © 2016 Elsevier Inc.

Bioorganic Chemistry

Candida parapsilosis: A versatile biocatalyst for organic oxidation-reduction reactions

Confocal microscopic studies with the resting cells of yeast, Candida parapsilosis ATCC 7330, a reportedly versatile biocatalyst for redox enzyme mediated preparation of optically pure secondary alcohols in high optical purities [enantiomeric excess (ee) up to >99%] and yields, revealed that the yeast cells had large vacuoles under the experimental conditions studied where the redox reaction takes place. A novel fluorescence method was developed using 1-(6-methoxynaphthalen-2-yl)ethanol to track the site of biotransformation within the cells. This alcohol, itself non-fluorescent, gets oxidized to produce a fluorescent ketone, 1-(6-methoxynaphthalen-2-yl)ethanone. Kinetic studies showed that the reaction occurs spontaneously and the products get released out of the cells in less time [5 mins]. The biotransformation was validated using HPLC.

Fulltext

Scientific Reports

Direct observation of redox reactions in Candida parapsilosis ATCC 7330 by Confocal microscopic studies

Enantiomerically pure β- and γ-nitro alcohols were prepared from their respective nitro ketones by asymmetric reduction mediated by the biocatalyst, Candida parapsilosis ATCC 7330 under optimized reaction conditions (ee up to >99%; yields up to 76%). This biocatalyst exhibits high chemoselectivity and reduces the keto group in preference to nitro group along with good enantioselectivity to produce enantiomerically enriched nitro alkanols. The asymmetric reduction of aliphatic nitro ketones was carried out in water with ethanol as cosolvent and glucose as cosubstrate using the whole cells of Candida parapsilosis ATCC 7330 in much lesser time (4 h). For the first time, the biocatalytic asymmetric reduction of the following ketones is reported here: 1-nitro-butan-2-one, 1-nitro-pentan-2-one, 3-methyl-1-nitro-butan-2-one and 1-cyclohexyl-2-nitroethanone to produce (R)-alcohols [ee up to 79%, yield up to 74%] and 1-nitro-hexan-2-one and 1-nitro-heptan-2-one to produce (S)-alcohols [ee up to 81%, yield up to 76%]. © The Royal Society of Chemistry.

RSC Advances

Enantio- &amp; chemo-selective preparation of enantiomerically enriched aliphatic nitro alcohols using Candida parapsilosis ATCC 7330

An efficient protocol for the construction of chromeno annulated pyrrolizine and thiazolizines derivatives through an in-situ formation of an azomethine ylides and zwitterionic intermediate followed by 1,3-dipolar cycloaddition reaction is described. This novel one-pot reaction paves the way for the successful assembly of salicaldehydes, dialkyl acetylenedicarboxylates and L-proline or thiazolidine-4-carboxylic acid in the presence of a basic catalyst. This domino process affords polycyclic chromeno annulated pyrrolizines and chromenothiazolizines in good yields. © 2018 Wiley-VCH Verlag GmbH &amp; Co. KGaA, Weinheim

ChemistrySelect

Regio- and Stereoselective Multicomponent Synthesis of Novel Chromeno-Annulated Pyrrolizine and Thiazolizine Scaffolds via 1,3-Dipolar Cycloaddition Reactions

Optically pure allylic alcohols and 4-phenylbutan-2-ols were prepared by oxidative kinetic resolution using whole cells of Candida parapsilosis ATCC 7330. Only the 'S' enantiomer is selectively oxidized to the corresponding keto compound (yield, 37-46%) leaving the 'R' alcohol (yield, 37-52% and ee 46 to >99%). The biocatalytic method is carried out under mild conditions at 20°C, pH 6.5 in phosphate buffer. © 2014 The Royal Society of Chemistry.

Enantioselective oxidation of secondary alcohols by Candida parapsilosis ATCC 7330

Asymmetric reduction of alkyl-3-oxobutanoates mediated by Candida parapsilosis ATCC 7330 resulted in optically pure alkyl-3-hydroxybutanoates in good yields (up to 72 %) and excellent enantiomeric excess (up to >99 %). A detailed and systematic optimisation study was necessary and was carried out to avoid the undesired transesterification reaction during the course of asymmetric reduction. Under optimised conditions, the (S)-alkyl hydroxyesters were produced predominantly except for the methyl ester which formed the (R)-enantiomer. To the best of our knowledge, the biocatalytic asymmetric reduction of isoamyl-3-oxobutanoate to (S)-isoamyl-3-hydroxybutanoate is reported here for the first time. © 2013 Springer Science+Business Media New York.

Applied Biochemistry and Biotechnology

Asymmetric reduction of alkyl-3-oxobutanoates by Candida parapsilosis ATCC 7330: Insights into solvent and substrate optimisation of the biocatalytic reaction

Biocatalytic preparation of various substituted N-phenylacetamides was carried out for the first time using whole cells of Candida parapsilosis ATCC 7330 under mild reaction conditions with excellent conversions (up to 93%) and good yields (up to 81%). Arylamine N-acetyltransferase (NAT) from whole cells of Candida parapsilosis ATCC 7330 is implicated in the N-acylation which is known to transfer the acetyl group from acetyl CoA (coenzyme A) to aromatic amines. Mechanistic investigation carried out using deuterated ethanol to find the source of acetyl CoA revealed that the reaction proceeds through the formation of acetaldehyde in situ, which is a potential source for the acetyl group of cytoplasmic acetyl CoA. Furthermore, experiments on regioselectivity, carried out with 2-phenylenediamine (2-PDA) resulted in a cyclised product 2-methyl benzimidazole (conversion 99%). The biocatalyst also mediates the cyclization of 3-(phenylamino)cyclohex-2-enones in the presence of the in situ generated acetaldehyde to form acridine-1,8-diones (conversion up to 70%), which is a green process reported here for the first time. © The Royal Society of Chemistry 2013.

A novel green route for the synthesis of N-phenylacetamides, benzimidazoles and acridinediones using Candida parapsilosis ATCC 7330

The stereochemical preference of the biocatalyst, Candida parapsilosis ATCC 7330, was investigated with respect to the E/Z configuration in the deracemization and the asymmetric reduction of aryl secondary alcohols and prochiral ketones, respectively. The biocatalyst preferred the E-isomers over Z-isomers as substrates as evidenced from the experimental results of >99% ee and up to 86% isolated yield for E-secondary alcohols. The synthesis of enantiomerically pure E-4-phenylbut-3-ene-1,2-diol (ee >99%, isolated yield 86%) by whole cell mediated deracemization is reported here for the first time. The geometric preference of the enzymes was confirmed by using the cell free extract of this biocatalyst. Mechanistic insights using in silico studies showed that the E-isomers when located in the active site are favourably placed with respect to the catalytic triad (Ser-Tyr-Lys) for hydride transfer from NADPH. © 2012 Elsevier Ltd. All rights reserved.

Tetrahedron Asymmetry

Stereochemical preference of Candida parapsilosis ATCC 7330 mediated deracemization: E- versus Z-aryl secondary alcohols

Racemic alkyl-2-hydroxy-4-arylbut-3-ynoates were deracemized to the (S)-alkyl-2-hydroxy-4-arylbut-3-ynoates in excellent enantiomeric excesses (up to &gt;99%) and good isolated yields (up to 81%) with the biocatalyst Candida parapsilosis ATCC 7330. The absolute configuration of the resulting enantiomer was assigned by 1H NMR using Mosher's method. © 2010 Elsevier Ltd. All rights reserved.

Biocatalytic deracemization of alkyl-2-hydroxy-4-arylbut-3-ynoates using whole cells of Candida parapsilosis ATCC 7330

Utilization of whole cell mediated deracemization in a chemoenzymatic synthesis of enantiomerically enriched polycyclic chromeno[4,3-b] pyrrolidines

Journal	Data powered by TypesetOrganic and Biomolecular Chemistry
Publisher	Data powered by TypesetRoyal Society of Chemistry
ISSN	14770520
Open Access	No