Recent advances in the stereoselective synthesis of 1,3-diols using biocatalysts

Gupta, Pankaj; Mahajan, Neha; Taneja, Subhash C.

doi:10.1039/c3cy00125c

Cited by 28 publications

(19 citation statements)

References 129 publications

(44 reference statements)

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“…As the chiral 3,5-dihydroxyheptanoic acid derivatives represent the key pharmacophore in all of the super-statins [8], major efforts of the academic and industrial communities have been made for their efficient preparation [38][39][40][41][42][43][44][45][46]. In the course of time, biocatalysis [47][48][49][50][51][52][53][54][55][56][57][58][59][60][61][62] evolved as an important platform for greener and more efficient and stereoselective synthesis of 3,5-dihydroxyheptanoic (heptenoic) acid precursors [63][64][65][66][67][68][69][70][71][72][73][74][75].…”

Section: Structure Of Advanced Super-statin Lateral Chain Precursorsmentioning

confidence: 99%

Recent Progress in the Synthesis of Super-Statins

Časar

2015

Topics in Heterocyclic Chemistry

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Super-statins now represent a mature class of marketed drugs that faces the patent cliff, as has already occurred for fluvastatin and atorvastatin and is approaching for rosuvastatin and pitavastatin. However, they continue to trigger huge scientific interest in terms of their efficient preparation. This is not surprising, as easier accessibility of super-statins will promote even bigger demand in the market and consequently the need for higher rates of the production and productivity. Therefore, the stimulus for the development of even more efficient synthetic approaches to the heterocyclic moieties of super-statins and their chiral lateralchain precursors is at a peak, as also for the assembly of the these two parts into super-statins. The present report summarizes recent developments in the field of the synthesis of super-statins published from 2010 to 2015. Emphasis is given to the analysis of novel approaches to the formation of the chiral statin lateral chain, with detailed discussion of the development of new routes to respective heterocyclic cores and the assembly of these key units into the final super-statin structure.

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Section: Structure Of Advanced Super-statin Lateral Chain Precursorsmentioning

confidence: 99%

Recent Progress in the Synthesis of Super-Statins

Časar

2015

Topics in Heterocyclic Chemistry

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“…In particular, the synthesis of 1,3‐diols is currently of considerable interest in organic chemistry, because of their use as building blocks for drugs or biologically active agents containing 1,3‐diol subunits . Recently, it was reported that the enantioselective organocatalytic aldol addition of acetone to aldehydes can be combined, in a one‐pot procedure, with the diastereoselective enzymatic reduction of the aldol's keto function.…”

Section: Introductionmentioning

confidence: 99%

“…[5] In particular,t he synthesis of 1,3-diols is currently of considerable interesti no rganic chemistry,b ecause of their use as buildingb locks for drugs or biologically active agentsc ontaining 1,3-diol subunits. [6,7] Recently,i tw as reported that the enantioselective organocatalytic aldol addition of acetonet o aldehydes can be combined, in ao ne-pot procedure, with the diastereoselective enzymatic reduction of the aldol's keto function. As ar esult,a ll four stereoisomeric1 ,3-diols can be produced in such aw ay,w ith diastereomeric ratios (dr values) typically > 20:1, and virtually perfect enantiomeric purity (ee > 98 %).…”

Section: Introductionmentioning

confidence: 99%

Screening, Molecular Cloning, and Biochemical Characterization of an Alcohol Dehydrogenase from Pichia pastoris Useful for the Kinetic Resolution of a Racemic β‐Hydroxy‐β‐trifluoromethyl Ketone

et al. 2016

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The stereoselective synthesis of chiral 1,3-diols with the aid of biocatalysts is an attractive tool in organic chemistry. Besides the reduction of diketones, an alternative approach consists of the stereoselective reduction of β-hydroxy ketones (aldols). Thus, we screened for an alcohol dehydrogenase (ADH) that would selectively reduce a β-hydroxy-β-trifluoromethyl ketone. One potential starting material for this process is readily available by aldol addition of acetone to 2,2,2-trifluoroacetophenone. Over 200 strains were screened, and only a few yeast strains showed stereoselective reduction activities. The enzyme responsible for the reduction of the β-hydroxy-β-trifluoromethyl ketone was identified after purification and subsequent MALDI-TOF mass spectrometric analysis. As a result, a new NADP(+) -dependent ADH from Pichia pastoris (PPADH) was identified and confirmed to be capable of stereospecific and diastereoselective reduction of the β-hydroxy-β-trifluoromethyl ketone to its corresponding 1,3-diol. The gene encoding PPADH was cloned and heterologously expressed in Escherichia coli BL21(DE3). To determine the influence of an N- or C-terminal His-tag fusion, three different recombinant plasmids were constructed. Interestingly, the variant with the N-terminal His-tag showed the highest activity; consequently, this variant was purified and characterized. Kinetic parameters and the dependency of activity on pH and temperature were determined. PPADH shows a substrate preference for the reduction of linear and branched aliphatic aldehydes. Surprisingly, the enzyme shows no comparable activity towards ketones other than the β-hydroxy-β-trifluoromethyl ketone.

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“…1,2 Biocatalysis is an economic and green approach for chiral resolution of a racemic mixture, 3 in which lipase (triacylglycerol ester hydrolases, EC 3.1.1.3) is among the most attractive targets. 1,2 Biocatalysis is an economic and green approach for chiral resolution of a racemic mixture, 3 in which lipase (triacylglycerol ester hydrolases, EC 3.1.1.3) is among the most attractive targets.…”

Section: Introductionmentioning

confidence: 99%

Enantioselectivity and catalysis improvements of Pseudomonas cepacia lipase with Tyr and Asp modification

Yue

et al. 2015

Catal. Sci. Technol.

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A concise strategy to improve the p-NPP Ĳp-nitrophenyl palmitate) catalytic activity and enantioselectivity towards secondary alcohols of Pseudomonas cepacia lipase (PcL) has been described. The PcL was modified by I 3 − , N-acetyl imidazole (NAI), 1-Ĳ3-dimethylaminopropyl)-3-ethylcarbodiimide (EDC) and ethylenediamine (EDA) in the absence or presence of n-hexane, respectively. After being modified by the four modification reagents, the enantioselectivity (E value) of the PcL towards secondary alcohols was enhanced by 2-to 4-fold. The catalytic activity of EDA-PcL was increased by about 6-fold. The matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS) analysis of modified PcL showed that Tyr 4 , Tyr 29 , Tyr 45 , Tyr 95 , Asp 36 and Asp 55 were the modified sites. When Tyr 29 was modified, the E value of PcL towards secondary alcohols was largely improved. MALDI-TOF-MS characterization and molecular dynamics simulation of the lipase indicated that Tyr 29 located inside the catalytic cavity had a significant impact on the E value. The strong steric hindrance of acetyl and iodine ion to the groups on the chiral center of the substrates is responsible for the improvement. In addition, the enhancement of hydrophobicity on the surface of the lipase due to the sidechain replacement of Asp with uncharged hydrophobic groups also improved the E value.

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Recent advances in the stereoselective synthesis of 1,3-diols using biocatalysts

Cited by 28 publications

References 129 publications

Recent Progress in the Synthesis of Super-Statins

Recent Progress in the Synthesis of Super-Statins

Screening, Molecular Cloning, and Biochemical Characterization of an Alcohol Dehydrogenase from Pichia pastoris Useful for the Kinetic Resolution of a Racemic β‐Hydroxy‐β‐trifluoromethyl Ketone

Enantioselectivity and catalysis improvements of Pseudomonas cepacia lipase with Tyr and Asp modification

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