104013-24-3

Upstream product

• 108-22-5 Isopropenyl acetate 
• 6531-13-1 1-[4-nitrophenyl]-1-ethanol 
• 22391-01-1 1-(4-nitrophenyl)-1-(acetyloxy)ethylene 
• 100-19-6 (4-nitrophenyl)ethanone 
• 108-05-4 vinyl acetate 
• 108-24-7 acetic anhydride 
• 19759-27-4 4-(α-acetoxyethyl)-1-nitrobenzene 
• 17279-31-1 (-)-(S)-N,N-dimethyl-1-phenylethylamine 

Downstream Products

• 6531-13-1 (1R)-1-(4-nitrophenyl)ethanol 

Relevant academic research and scientific papers

A C2-symmetric metallocene-pyrrolidinopyridine nucleophilic catalyst for asymmetric synthesis

A C2-symmetric nucleophilic catalyst, (R,R)-3,5-diferrocenyl-4- (2′,5′-dimethylpyrrolidino)pyridine, was synthesised in three steps from commercially available (S,S)-hexane-2,5-diol. Application to the kinetic resolution of secondary alcohols (0.5 mol% loading) resulted in selectivity factors (s) of up to 6. Georg Thieme Verlag Stuttgart.

LipG9-mediated enzymatic kinetic resolution of racemates: Expanding the substrate-scope for a metagenomic lipase

Enzymes are the main biocatalysts of biological systems and nowadays they play an important role in asymmetric organic synthesis. Microorganisms are the main source for enzymes, however, just a very small portion of them are culturable at lab conditions and, as an alternative, metagenomics approaches allow new enzymes to be accessed from so-called “non-culturable” microorganisms. Several classes of metagenomic enzymes have been described in literature. Nevertheless, studies about their potential for asymmetric biotransformation are underexploited. Therefore, we present our recent efforts to establish the substrate-scope of LipG9, a metagenomic lipase, in enzymatic kinetic resolution (EKR) of chiral substances. LipG9 was previously isolated, immobilized and successfully applied in EKR of aliphatic alcohols. In this study, a series of resolvable chiral substances were assayed with LipG9, and secondary benzyl alcohols/esters were preferentially resolved in a much superior enantioselectivity (E > 200) than those described for aliphatic alcohols (E from 4 to 63). In an opposite way, Im-LipG9 did not present activity for tertiary alcohols, amines and lactones. When compared to commercial lipases, Im-LipG9 enantioselectivity was superior to Candida rugosa lipase and equivalent to Candida antarctica lipase B. Thus, the chemo and enantioselectivity of LipG9 in EKR reactions were identified and its potential for asymmetric synthetic approaches was demonstrated.

Separation of enantiopure m-substituted 1-phenylethanols in high space-time yield using Bacillus subtilis esterase

A recombinant Bacillus subtilis esterase (BsE) expressed in E. coli was found to exhibit excellent enantioselectivity (E was always greater than 100) towards m-substituted 1-phenylethanol acetates in the enantioselective hydrolysis reaction. An explanation for the high enantioselectivity observed towards these substrates was provided by molecular modeling. Moreover, the BsE also showed strong tolerance towards a high concentration of m-substituted 1-phenylethanol acetates (up to 1 M). Based on these excellent catalytic properties of BsE, a kind of m-substituted 1-phenylethanols, (R)-1-(3-chlorophenyl)ethanol, was efficiently synthesized in space-time yield of 920 g per L per day and 97% ee, indicating that the BsE was considered as a potentially ideal and promising biocatalyst for large-scale production of optically active m-substituted 1-phenylethanols. The Royal Society of Chemistry 2013.

Modular P-OP ligands in rhodium-mediated asymmetric hydrogenation: A comparative catalysis study

Highly efficient and enantioselective hydrogenation reactions for α-(acylamino)acrylates, itaconic acid derivatives and analogues, α-substituted enol ester derivatives, and α-arylenamides (25 substrates) catalyzed by chiral cationic rhodium complexes of a set of P-OP ligands have been developed. The catalytic systems derived from these P-OP ligands provided a straightforward access to enantiomerically enriched α-amino acid, carboxylic acid, amine, and alcohol derivatives that are valuable chiral building blocks. Excellent efficiencies (full conversion in all cases) and extremely high enantiomeric excesses (94-99% ee) were achieved for a wide range of α-substituted enol ester derivatives, regardless of the substitution pattern. The R-oxy group of the ligand (methoxy or triphenylmethoxy) strongly influences the enantioselectivity and catalytic activity. Greater steric bulk around the metal centre correlated to greater (or similar) enantioselectivity, but also to slower hydrogenation. Furthermore, the hydrogenation rates observed with the four model substrates follow the same trend, independently of the R-oxy group of the ligand: methyl 2-acetamidoacrylate>dimethyl itaconate>1-phenylvinyl acetate>N-(1- phenylvinyl)acetamide. A substrate-to-catalyst ratio (S/C) of up to 10,000:1 was sufficient for total hydrogenation of a model substrate of intermediate reactivity (dimethyl itaconate), and did not imply any loss in conversion or enantioselectivity. Copyright

Chiral rhodium complexes derived from electron-rich phosphine-phosphites as asymmetric hydrogenation catalysts

Two new chiral cationic rhodium(I) complexes derived from electron-rich dicyclohexylphosphine-phosphite ligands were prepared from enantiopure Sharpless epoxy ethers. The best-performing catalyst system, which bears a less bulky methyl ether moiety, exhibited remarkably high enantioselectivity (up to 99% ee) and reactivity (up to >2500 TON) in asymmetric hydrogenation reactions of various functionalized alkenes (α-(acylamino)acrylates, itaconic acid derivatives, α-substituted enol esters and α-arylenamides). Our synthetic methodology has been successfully applied to the enantioselective synthesis of the antiepileptic drug (R)-lacosamide (Vimpat).

Dynamic kinetic resolution of a wide range of secondary alcohols: Cooperation of dicarbonylchlorido(pentabenzylcyclopentadienyl)ruthenium and CAL-B

The substrate scope in the dynamic kinetic resolution ofsecondary alcohols was studied by using 31 structurallydifferent alcohols and isopropenyl acetate in the presence ofdicarbonylchlorido(pentabenzylcyclopentadienyl)rutheniumand Candida antarctica lipase B (Novozym 435, CAL-B) in toluene. The enzyme and the ruthenium complex were shown to function in a highly compatible manner allowing the conversion of the racemic alcohols into the (R)-acetates in practically theoretical yields and, in most cases, ee values exceeding 99%. The results are fully comparable to those published previously by using earlier reported, state-of-the-art ruthenium-based catalysts for the alcohol racemization. A clear benefit of the dicarbonylchlorido(pentabenzylcyclopentadienyl)ruthenium system, when compared to other (cyclopentadienyl)ruthenium racemization catalysts, is its simple and cost-efficient preparation. The substrate scope of 31 secondary alcohols was studied in the dynamic kinetic resolution by utilizing dicarbonylchlorido(pentabenzylcyclopentadienyl)rutheniumand Candida antarctica lipase B (CAL-B) in the acylation with isopropenyl acetate in toluene at room temperature. The secondary alcohols were transformed into highly enantiopure (R)-acetates (in most cases ee > 99%) in close to quantitative isolatedyields. Copyright

Evaluation of snake venom phospholipase A2: Hydrolysis of non-natural esters

Phospholipase A2 from the rattlesnake Crotalus durissus terrificus was employed for the first time to test its enantioseletivity on the hydrolysis of different non-natural esters. It was observed that the structure of this small enzyme is restrictive in the choice of its lipase action with non-natural substrates. Two forms of the enzyme were used; free and as its cross-linked enzyme aggregate (CLEA). With all substrates, the free enzyme showed activity similar to the CLEA preparation. The advantage of the CLEA phospholipase is the possibility to reuse it in several consecutive reactions without a decrease of activity and selectivity with good but higher yields and ee than with the free enzyme.

A tandem and fully enzymatic procedure for the green resolution of chiral alcohols: Acylation and deacylation in non-aqueous media

A green and fully enzymatic procedure for the resolution of chiral alcohols through lipase/esterase-catalyzed acylation and subsequent lipase-catalyzed aminolysis using anhydrous ammonia was demonstrated. Both enantiomers can be obtained in high ee values (up to >99%) under ambient reaction conditions. The solvent and acyl donors can be recycled, and the enzyme can be reused for up to five times.

Enzymatic kinetic resolution of (RS)-1-(phenyl)ethanols by Burkholderia cepacia lipase immobilized on magnetic nanoparticles

Lipase from Burkholderia cepacia immobilized on superparamagnetic nanoparticles using adsorption and chemisorption methodologies was efficiently applied as recyclable biocatalyst in the enzymatic kinetic resolution of (RS)-1-(phenyl)ethanols via transesterification reactions. (R)-Esters and the remaining (S)-alcohols were obtained with excellent enantiomeric excess (> 99percent), which corresponds to a perfect process of enzymatic kinetic resolution (conversion 50percent, E > 200). The transesterification reactions catalysed with B. cepacia lipase immobilized by the glutaraldehyde method showed the best results in terms of reusability, preserving the enzyme activity (conversion 50percent, E > 200) for at least 8 successive cycles.

Escherichia coli BioH: A highly enantioselective and organic solvent tolerant esterase for kinetic resolution of sec-alcohols

Escherichia coli BioH, which is obligatory for biotin synthesis, was found to be an organic solvent tolerant esterase with high enantioselectivity for the kinetic resolution of sec-alcohols using free enzyme powder. With this esterase, a variety of racemic sec-alcohols were efficiently resolved with ee values of up to 99%.