Enzymatic resolution of an amine under solvent-free conditions with diethyl malonate as reagent for acylation

Uthoff, Florian; Reimer, Anna; Liese, Andreas; Gröger, Harald

doi:10.1016/j.scp.2016.12.002

Cited by 11 publications

(4 citation statements)

References 26 publications

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“…In addition, diethylmalonate is used as an acylation reagent in the initial screening experiments, as Gröger et al. recently showed that this acyl donor enables efficient enzymatic resolutions of 1-arylethylamines. , The results, which are described in the Supporting Information (Table S3), reveal lipase B from Candida antarctica (CAL-B) as the most suitable enzyme for the kinetic resolution of 1-aminoindane rac - 24 .…”

Section: Resultsmentioning

confidence: 99%

Chemoenzymatic Synthesis of a Chiral Ozanimod Key Intermediate Starting from Naphthalene as Cheap Petrochemical Feedstock

et al. 2019

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Ozanimod represents a recently developed, promising active pharmaceutical ingredient (API) molecule in combating multiple sclerosis. Addressing the goal of a scalable, economically attractive, and technically feasible process for the manufacture of this drug, a novel alternative synthetic approach toward (S)-4-cyano-1-aminoindane as a chiral key intermediate for ozanimod has been developed. The total synthesis of this intermediate is based on the utilization of naphthalene as a readily accessible, economically attractive, and thus favorable petrochemical starting material. At first, naphthalene is transformed into 4-carboxy-indanone within a four-step process by means of an initial Birch reduction, followed by an isomerization of the CC double bond, oxidative CC cleavage, and intramolecular Friedel–Crafts acylation. The transformation of the 4-carboxy-indanone into (S)-4-cyano-1-aminoindane then represents the key step for introducing the chirality and the desired absolute S configuration. When evaluating complementary biocatalytic approaches based on the use of a lipase and transaminase, respectively, the combination of a chemical reductive amination of the 4-carboxyindanone followed by a subsequent lipase-catalyzed resolution turned out to be the most efficient route, leading to the desired key intermediate (S)-4-cyano-1-aminoindane in satisfactory yield and with excellent enantiomeric excess of 99%.

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Section: Resultsmentioning

confidence: 99%

Chemoenzymatic Synthesis of a Chiral Ozanimod Key Intermediate Starting from Naphthalene as Cheap Petrochemical Feedstock

et al. 2019

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“…Diethyl malonate has been shown to be an efficient acyl donor in lipase-catalyzed resolution of aromatic amines [26]. Subsequently, a robust and efficient solvent-free method was developed for the kinetic resolution of racemic 1-phenylethane-1-amine with diethyl malonate catalyzed by immobilized CaLB [27].…”

Section: Introductionmentioning

confidence: 99%

Diisopropyl Malonate as Acylating Agent in Kinetic Resolution of Chiral Amines with Lipase B from Candida antarctica

Szemes

Malta-Lakó

Tóth

et al. 2022

Period. Polytech. Chem. Eng.

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Activity of diisopropyl malonate (2) as a novel acylating agent was investigated in kinetic resolution (KR) of various racemic amines [(±)-1a-d] catalyzed by lipase B from Candida antarctica. Diisopropyl malonate (2) proved to be effective acylating agent with four racemic amines [(±)-2-aminoheptane, (±)-1-methoxy-2-propylamine, (±)-1-phenylethylamine and (±)-4-phenylbutan-2-amine; (±)-1a-d, respectively] selected for this study. The lipase-catalyzed acylation of the amines (±)-1a-d with 2 proceeded with good conversions (44.9–52.1%) and provided the expected (R)-amides [(R)-3a-d] in moderate to excellent yields (51–98%) with high enantiomeric excess (ee(R)-3a-d 92.0–99.9%) after 4 h reaction time under mild reaction conditions in batch mode. The best conversion (50%) combined with high enantiomeric purity (ee(R)-2d > 99%ee) was achieved in the KR from racemic 2-aminoheptane (±)-1a. The four novel (R)-amides [(R)-3a-d] were isolated and properly characterized.

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“…Classical enzymatic kinetic resolution (EKR) relies on a simple and well-known phenomenon that due to the chirality of the active site of the enzyme, one enantiomer fits better into the active site than its counterpart and is therefore converted at a higher rate . The EKR methodology has become one of the most prevalent approaches used nowadays in the synthesis of optically active compounds (especially chiral sec -alcohols/esters, − carboxylic acids/esters, − and primary amines/amides − ) mostly because of the possibility of obtaining both enantiomeric forms of the respective racemic substrates in a single run at relatively mild temperatures. However, the applicability of the EKR process on an industrial scale is strongly limited as this method is not attractive from the practical point of view due to several drawbacks mainly associated with low reaction yields (in the best-case scenario, only one substrate enantiomer reacts for a theoretical maximum yield of 50%) and high cost of isolation and purification operations of the desired products.…”

Section: Introductionmentioning

confidence: 99%

From Waste to Value—Direct Utilization of α-Angelica Lactone as a Nonconventional Irreversible Acylating Agent in a Chromatography-Free Lipase-Catalyzed KR Approach toward sec-Alcohols

Poterała

Borowiecki

2021

ACS Sustainable Chem. Eng.

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Although the classical enzymatic kinetic resolutions (EKRs) are among the most important reactions in biocatalysis, the requirement of application of chromatographic purification technique, which is responsible for the generation of large amounts of waste organic solvents, is its major drawback. To minimize the environmental impact of such attempts and to address the current sustainability challenges, we decided to develop a novel EKR methodology, which relies on the usage of cheap, fully renewable, nontoxic, and irreversible acyl group donor reagent, namely, α-angelica lactone. The employed activated enol lactone-based acyl donor proved to be a versatile reagent enabling efficient and highly enantioselective (up to E ≫ 500) lipase-catalyzed resolution of a set of racemic sec-alcohols with up to >99% ee and near to quantitative isolation yields according to conversions achieved during the respective EKR procedure. Moreover, α-angelica lactone provided, in this case, an ability of fast and straightforward separation of the enzymatic reactions’ products via chromatography-free reactive liquid–liquid extraction (LLE) workup using either saturated aqueous sodium bisulfate in dimethylformamide (DMF) or Girard’s P reagent in a mixture of EtOH/AcOH (90:10, v/v), respectively. The NaHSO3/DMF LLE workup and the subsequent reisolation of the respective levulinate from the aqueous layer turned out to be less efficient than a separation with Girard’s P reagent. The selective LLE of optically active levulinate-Girard P-hydrazones from the respective alcohols and further hydrolysis of the respective hydrazides with diluted HClaq. could be performed with high levels of recovery of both EKR products isolated usually without loss of enantiomeric purity.

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Enzymatic resolution of an amine under solvent-free conditions with diethyl malonate as reagent for acylation

Cited by 11 publications

References 26 publications

Chemoenzymatic Synthesis of a Chiral Ozanimod Key Intermediate Starting from Naphthalene as Cheap Petrochemical Feedstock

Chemoenzymatic Synthesis of a Chiral Ozanimod Key Intermediate Starting from Naphthalene as Cheap Petrochemical Feedstock

Diisopropyl Malonate as Acylating Agent in Kinetic Resolution of Chiral Amines with Lipase B from Candida antarctica

From Waste to Value—Direct Utilization of α-Angelica Lactone as a Nonconventional Irreversible Acylating Agent in a Chromatography-Free Lipase-Catalyzed KR Approach toward sec-Alcohols

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