One-pot synthesis of Wieland–Miescher ketone by enzymes

Lai, Yi‐Feng; Zhang, Peng-Fei

doi:10.1007/s11164-013-1512-6

Cited by 8 publications

(18 citation statements)

References 17 publications

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“…We began by assembling a 14-member library of commercially available lipases preparations, selecting lipases previously reported to catalyze C-C bond forming reactions (Porcine pancreatic lipase, Candida antarctica lipase B) [11,12,14,17], in addition to lipase preparations with unknown biocatalytic properties in promiscuous biocatalysis (Wheat germ lipase). Biocatalytic potential of the lipase library was then assessed for synthesis of the Wieland-Miescher ketone from methyl vinyl ketone and 2-methyl-1,3-cyclohexanedione using recently reported literature conditions.…”

Section: Resultsmentioning

confidence: 99%

“…Biocatalytic potential of the lipase library was then assessed for synthesis of the Wieland-Miescher ketone from methyl vinyl ketone and 2-methyl-1,3-cyclohexanedione using recently reported literature conditions. [12] In order to rapidly assess biocatalytic potential of the library, an LC/MS method was developed (Materials and Methods) that detected only the main fragmentation pattern Wieland-Miescher ketone product ( Figure 2). Reaction yields were determined for each lipase using a standard curve ( Fig.…”

Section: Resultsmentioning

confidence: 99%

“…[9,10] The catalytic promiscuity of lipases has been the foundation on which various studies have been conducted to demonstrate a broad spectrum of lipase catalyzed organic transformations including the Robinson annulation, the Knoevenagel condensation, and the Morita-Baylis-Hillman reaction. [7,11,12] Despite intensive investigation of the lipase biocatalysis, unanswered questions remain regarding fundamental aspects of their propensity for promiscuous catalysis. [13] Some studies have identified crude lipase preparations with biocatalytic properties presuming, but not demonstrating, that lipase, in particular the lipase active site responsible for the in vivo hydrolysis of fatty acids ( Fig.…”

Section: Introductionmentioning

confidence: 99%

“…1C). [12,14] While in many instances the lipase activity present in crude lipase preparations is directly responsible for promiscuous catalysis, this is not always the case. [15,16] In the absence of a more thorough characterization of these catalytic moieties, it is challenging to improve on the initial findings through the now-standard means of rational design and/or directed evolution.…”

Section: Introductionmentioning

confidence: 99%

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Screening of Biocatalysts for Synthesis of The Wieland-Miescher Ketone

Patel¹,

Green²,

Burch³

et al. 2020

Preprint

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Lipases, a versatile class of biocatalysts, have been shown to function in non-aqueous media/organic solvents and to possess promiscuous catalytic activity for a wide range of organic transformations. In this study, we explore the biocatalytic properties of a library of commercially available lipases by screening them for catalysis of a one-pot synthesis of Wieland-Miescher Ketone, an important intermediate in the synthesis of biologically active compounds such as steroids and terpenoids, from methyl vinyl ketone and 2-methyl-1,3-cyclohexanedione. As a direct outgrowth of this screen, we have created an optimized procedure for Wieland-Miescher Ketone (WMK) synthesis using crude lipase preparations, characterizing both reaction yield and enantiomeric excess. We have also identified principal components of the crude lipase mixture through proteomics and present evidence for a non-lipolytic origin of the observed catalysis. Finally, using the optimized conditions developed in this study, we propose a general absorbance-based screening methodology for assessing biocatalytic potential of crude enzyme preparations for synthesis of WMK.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Screening of Biocatalysts for Synthesis of The Wieland-Miescher Ketone

Patel¹,

Green²,

Burch³

et al. 2020

Preprint

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“…[20][21][22] While a lipase-catalysed domino reaction of Wieland-Miescher ketone was recently reported, no stereoselectivity was observed. [23] (Scheme1)…”

Section: Introductionmentioning

confidence: 99%

Lipase-catalyzed domino Michael–aldol reaction of 2-methyl-1,3-cycloalkanedione and methyl vinyl ketone for the synthesis of bicyclic compounds

Sano

Kohari

Nakano

et al. 2015

Synthetic Communications

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Synthesis of bicyclic compounds was achieved via a lipase-catalysed, stereoselective, domino Michael-aldol reaction of 2-methyl-1,3-cycloalkanedione and methyl vinyl ketone. Appropriate reaction conditions, including the type of enzyme, solvent, and temperature, were determined. In addition, the effects of solvent polarity and addtives were investigated. The reaction proceeded in the presence of lipase AS in a solution of 20% acetone in dimethylsulfoxide (DMSO) at 10°C for 8 days, followed by the addition of p-toluenesulfonic acid (TsOH) to afford bicyclic compounds in 51%-83% yields with moderate stereoselectivity. Although this domino Michael-aldol reaction showed only moderate stereoselectivity, even with the acid-supported enhancement of the reaction, these results represent potential new applications for lipase.

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Discovery and Engineering of an Ene‐reductase for Kinetic Resolution and Cascade Reduction of Hajos‐Parrish/Wieland‐Miescher Ketones

Chen

et al. 2023

Adv Synth Catal

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Ene‐reductase (ERED)‐catalyzed asymmetric reduction of α,β‐unsaturated ketones is an attractive method in organic synthesis. Through the discovery and further structure‐guided protein engineering of BsER, an ERED from Bacillus subtilis, the selective bio‐reduction of the well‐known building blocks Hajos‐Parrish ketone (HPK, 1 a) and Wieland‐Miescher ketone (WMK, 1 b) was achieved in this study. The optically pure (R)‐HPK ((R)‐1 a) and (R)‐WMK ((R)‐1 b) with corresponding >99% and 98% enantiomeric excess (ee) values were obtained by kinetic resolution of the racemic substrates. To the best of our knowledge, this is the first example of ERED mediated kinetic resolution of rac‐HPK and rac‐WMK. In addition, the reduction products cis‐7a‐methylhexahydro‐1H‐indene‐1,5(4H)‐dione (cis‐2 a) and cis‐8a‐methylhexahydronaphtha‐ lene‐1,6(2H,5H)‐dione (cis‐2 b) with high diastereomeric ratios (dr) were also obtained. We also developed four routes of biocatalytic cascade reduction involving BsER and ketoreductases (KREDs). Using optimized ERED‐KRED and KRED‐ERED cascades, (S)‐HPK ((S)‐1 a) and (S)‐WMK ((S)‐1 b) could be reduced stepwise, yielding the bioactive products all with >91% purity. This study presents a biocatalytic strategy for the kinetic resolution and cascade reduction of HPK and WMK (1 a and 1 b).magnified image

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One-pot synthesis of Wieland–Miescher ketone by enzymes

Cited by 8 publications

References 17 publications

Screening of Biocatalysts for Synthesis of The Wieland-Miescher Ketone

Screening of Biocatalysts for Synthesis of The Wieland-Miescher Ketone

Lipase-catalyzed domino Michael–aldol reaction of 2-methyl-1,3-cycloalkanedione and methyl vinyl ketone for the synthesis of bicyclic compounds

Discovery and Engineering of an Ene‐reductase for Kinetic Resolution and Cascade Reduction of Hajos‐Parrish/Wieland‐Miescher Ketones

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