Biocatalytic approaches for enantio and diastereoselective synthesis of chiral β-nitroalcohols

Rao, D. H. Sreenivasa; Chatterjee, Ayon; Padhi, Santosh Kumar

doi:10.1039/d0ob02019b

Cited by 18 publications

(11 citation statements)

References 60 publications

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“…The synthesis then is a biocatalytic Henry reaction (Scheme 4). 40,41,47,48 Recent developments have focussed on even more enzymes from unusual sources such as millipedes 44,[51][52][53] and bacteria, [54][55][56] the exploration of evolutionary ancestors 57 and other methods to interconvert HNL activity with other enzyme activities, in particular hydrolase activity. 58 Reaction engineering with a special focus of the application of HNLs in flow has recently led to promising results.…”

Section: C-c-bond Forming Reactionsmentioning

confidence: 99%

Biocatalysis making waves in organic chemistry

2022

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Section: C-c-bond Forming Reactionsmentioning

confidence: 99%

Biocatalysis making waves in organic chemistry

2022

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“…Details about the study is already reviewed elsewhere. [37] To summarize this section, several HNLs were immobilized and studied for biocatalysis in last seven years. Immobilization of HNLs has improved various biocatalytic properties, i. e. rate (MeHNL), stability at low pH (AtHNL), recyclability (AtHNL, BmHNL, PaHNL, ParsHNL), high thermostability (AtHNL), storage stability (DtHNL, ParsHNL), and enantioselectivity (BmHNL).…”

Section: Asymmetric Synthesis Using Non-natural Nucleophile (Nitromet...mentioning

confidence: 99%

Hydroxynitrile Lyase Discovery, Engineering, and Promiscuity towards Asymmetric Synthesis: Recent Progress

Priya,

Padhi

2023

Eur J Org Chem

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Hydroxynitrile lyases (HNLs) primarily catalyze the stereoselective synthesis of cyanohydrins, but some of them also carry out asymmetric nitroaldol synthesis (Henry reaction). By virtue of the importance of asymmetric C‐C bond formation, and the wide application of chiral cyanohydrins and β‐nitroalcohols, HNLs have gained significance in organic synthesis. Over the years new HNLs have been discovered and their synthetic scope are evaluated. Engineering of HNLs has contributed towards increasing not only the catalytic toolbox but also broad substrate selectivity, stereoselectivity, enzyme stability and application of the enzymes for different transformations other than the conventional ones. This review describes the recent discoveries of diverse hydroxynitrile lyases, and the developments to date since 2016, with respect to their biocatalytic applications in the asymmetric synthesis using both natural and promiscuous reactions.

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“…Chiral β-nitro alcohols are compounds containing two versatile functional groups, a hydroxyl and a nitro group, attached to adjacent carbon centres of which either one or both are asymmetric. These compounds are precursors of chiral β-amino alcohols, which are important chiral building blocks for the synthesis of bioactive compounds used as pharmaceutical ingredients such as bestatin, ephedrine, norephedrine, and sphingosine [1,2]. The nitroaldol synthesis (Henry reaction) of β-nitro alcohols is base catalysed and many bases have been evaluated.…”

Section: Introductionmentioning

confidence: 99%

“…Biocatalysis is an alternative method for producing β-nitro alcohols with high selectivity under mild reaction conditions. Six biocatalytic approaches have been described as recently reviewed [1]. Of these, the HNL catalysed Henry reaction is particularly attractive as a new carbon-carbon bond and a stereocentre is established simultaneously.…”

Section: Introductionmentioning

confidence: 99%

Batch and Flow Nitroaldol Synthesis Catalysed by Granulicella tundricola Hydroxynitrile Lyase Immobilised on Celite R-633

et al. 2022

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Granulicella tundricola hydroxynitrile lyase (GtHNL) catalyses the synthesis of chiral (R)-cyanohydrins and (R)-β-nitro alcohols. The triple variant GtHNL-A40H/V42T/Q110H (GtHNL-3V) was immobilised on Celite R-633 and used in monophasic MTBE saturated with 100 mM KPi buffer pH 7 for the synthesis of (R)-2-nitro-1-phenylethanol (NPE) in batch and continuous flow systems. Nitromethane was used as a nucleophile. A total of 82% of (R)-NPE and excellent enantioselectivity (>99%) were achieved in the batch system after 24 hours of reaction time. GtHNL-3V on Celite R-633 was successfully recycled five times. During more recycling steps a significant decrease in yield was observed while the enantioselectivity remained excellent over eight cycles. The use of a flow system enabled the continuous synthesis of (R)-NPE. A total of 15% formation of (R)-NPE was reached using a flow rate of 0.1 mL min−1; unfortunately, the enzyme was not stable, and the yield decreased to 4% after 4 hours on stream. A similar yield was observed during 15 hours at a rate of 0.01 mL min−1. Surprisingly the use of a continuous flow system did not facilitate the process intensification. In fact, the batch system displayed a space-time-yield (STY/mgenzyme) of 0.10 g L−1 h−1 mgenzyme−1 whereas the flow system displayed 0.02 and 0.003 g L−1 h−1 mgenzyme−1 at 0.1 and 0.01 mL min−1, respectively. In general, the addition of 1 M nitromethane potentially changed the polarity of the reaction mixture affecting the stability of Celite-GtHNL-3V. The nature of the batch system maintained the reaction conditions better than the flow system. The higher yield and productivity observed for the batch system show that it is a superior system for the synthesis of (R)-NPE compared with the flow approach.

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Biocatalytic approaches for enantio and diastereoselective synthesis of chiral β-nitroalcohols

Abstract: Chiral β-nitroalcohols find significant application in organic synthesis due to the versatile reactivity of hydroxyl, and nitro functionality located to one or two vicinal asymmetric centers. They are key building...

Cited by 18 publications

References 60 publications

Biocatalysis making waves in organic chemistry

Biocatalysis making waves in organic chemistry

Hydroxynitrile Lyase Discovery, Engineering, and Promiscuity towards Asymmetric Synthesis: Recent Progress

Batch and Flow Nitroaldol Synthesis Catalysed by Granulicella tundricola Hydroxynitrile Lyase Immobilised on Celite R-633

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