- Optimization of 2-alkoxyacetates as acylating agent for enzymatic kinetic resolution of chiral amines
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In this study, the activity of acetic acid esters modified with electron withdrawing 2-alkoxy-groups was investigated as acylating agent in kinetic resolution (KR) of racemic amines. A homologous series of the isopropyl esters of four 2-alkoxyacetic acids (2-methoxy-, 2-ethoxy-, 2-propoxy- and 2-butoxyacetic acids) were prepared and investigated for enantiomer selective N-acylation, catalyzed by lipase B from Candida antarctica, under batch and continuous-flow conditions. In the first set of experiments, isopropyl 2-propoxyacetate showed the highest effectivity with all of the four racemic amines [(±)-1-phenylethylamine, (±)-4-phenylbutan-2-amine, (±)-heptan-2-amine and (±)-1-methoxypropane-2-amine] in the set enabling excellent conversions (≥46%) and enantiomeric excess values (ee ≥ 99%) with each amines in continuous-flow mode KRs under the optimized reaction conditions. In a second set of experiments, KRs of five additional amines – being substituted derivatives of (±)-1-phenylethylamine – further demonstrated the usefulness of isopropyl 2-propoxyacetate – being the best acylating agent in the first set of KRs – in KRs leading to (R)-N-propoxyacetamides with high ee values (≥99.8%).
- Oláh, Márk,Kovács, Dániel,Katona, Gabriel,Hornyánszky, Gábor,Poppe, László
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- Efficient enzymatic kinetic resolution of 2-heptylamine with a highly active acyl donor
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Novozyme435 facilitated kinetic resolution of 2-heptylamine was here presented. Methyl methoxyacetate was used as acyl donor. A survey of influencing factors including hydrogen bonding effect, solvent effect, steric effect, temperature and the amount of acyl donor were investigated in detail. At the optimum conditions, the enantiomeric separation was successfully obtained within 8 h at 20 °C, and gave high conversion and optical purity of (R)-2-heptylamine, 48.9% and over 99% respectively. The immobilized lipase B was found to be suitable for the enantiomeric separation of aliphatic amines with good recyclability.
- Sun, Jian-Hua,Dai, Rong-Ji,Meng, Wei-Wei,Deng, Yu-Lin
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experimental part
p. 987 - 991
(2010/11/16)
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- Fully enzymatic resolution of chiral amines: Acylation and deacylation in the presence of Candida antarctica lipase B
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A fully enzymatic methodology for the resolution of chiral amines has been demonstrated. Candida antarctica lipase B (CaLB)-catalyzed acylation with N-methyl-and N-phenylglycine, as well as analogues having the general formula R1-X-CH2CO2R2 (R1 = Me, Ph; X = O, S) afforded the corresponding enantioenriched amides, which were subsequently enzymatically hydrolyzed. Surprisingly, CaLB also proved to be the catalyst of choice for this latter step. The heteroatom in the acyl donor profoundly influences both the enzymatic acylation and deacylation; the O-substituted reagents performed best with regard to enantioselectivity as well as reaction rate in synthesis and hydrolysis.
- Ismail, Hilda,Lau, Rute Madeira,Van Rantwijk, Fred,Sheldon, Roger A.
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experimental part
p. 1511 - 1516
(2009/08/07)
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