Enantioselective esterification of(R,S)-2-(4-methylphenyl)propionic acid via Novozym 435:Optimization and application

This paper reports on the resolution of(R,S)-2-(4-methylphenyl)propionic acid(MPPA)enantiomers by enzymatic esterification in organic solvent.Novozym 435(CALB)has the best catalytic performance compared with other lipases.Of the alcohols screened,n-hexanol is the best acyl acceptor and gives the highest enzyme activity and enantioselectivity in n-hexane.Response surface methodology(RSM)was used to evaluate the influence of the factors,such as temperature,enzyme amount,substrate concentration and reaction time on the substrate conversion(c)and enantiomeric excess(ee).The correlation coefficient R2 for enantiomeric excess and the conversion are 0.9827 and 0.9910,respectively,indicating that can accurately predict the experimental results.By simulation and optimization,the optimal conditions were obtained,involving 600 mmol·L^-1 MPPA concentration(0.60 mmol),850 mmol·L^-1 hexanol concentration(0.85 mmol),58 mg enzyme amount,75℃temperature and 4.5 h reaction time,respectively.Under the optimized conditions,the experimental values of conversion and enantiomeric excess were 89.34%and 97.84%,respectively,which are in good agreement with the model predictions.

Synthesis of (R)(E)-3,7-Dimethyl-2-octene-1,8-dioic Acid, a Copulation Released Pheromone Component of Azuki Bean Weevil

Started from 5-hydroxy-2-pentanone, (R)(E)-3,7-dimethyl-2-octene-1,8-dioic acid, callosobruchusic acid, was synthesized via five steps with D-(-)-camphor sultam as the chiral auxiliary. It was of good optical purity and yield.

Crystal Structure and Biological Activities of (R)-N′-[2-(4-Methoxy-6-chloro)-pyrimidinyl]-N-[3-methyl-2-(4-chlorophenyl)butyryl]-urea

The title compound （R）-N′-[2-（4-methoxy-6-chloro）-pyrimidyl]-N-[3-methyl-2-（4- chlorophenyl）butyryl]-urea has been synthesized, and its crystal structure and biological behaviors were studied. Crystallographic data： C17H18C12N4O3, Mr = 397.25, monoclinic, space group P21/c, a = 12.331（2）, b = 14.025（3）, c = 23.085（5） A, β = 99.607（4）°, Z = 8, V = 3936.2（13） A3, Dc = 1.341 g/cm^3, F（000） = 1648, R = 0.0718, wR = 0.1585 and/t（MoKα） = 0.353 mm^-1. The preliminary biological tests showed that the title compound has definite insecticidal and fungicidal activities.

Design, Synthesis, Antifungal Activities and SARs of （R）-2-Aryl-4,5-dihydrothiazole-4-carboxylic Acid Derivatives

Based on the structure of natural product 2-aryl-4,5-dihydrothiazole-4-carboxylic acid, a series of novel （R）-2-aryl-4,5-dihydrothiazole-4-carboxylic acid derivatives were designed and synthesized. Their structures were characterized by ^1H NMR, ^13C NMR and HRMS. The single crystal structure of compound 9b was determined by X-ray diffraction analysis. The antifungal activities were evaluated for the first time. The bioassay results indicated that most compounds exhibited moderate to good antifungal activities. The antifungal activities of compound 13a （against Cercospora arachidicola Hori）, 13d （against Alternaria solani）, and 16e （against Cercospora arachidieola Hori） were 61.9%, 67.3% and 61.9%, respectively, which are higher than those of the commercial fungicides chlorothalonil and carbendazim. Moreover, compound 13d exhibited excellent antifungal activities against 7 kinds of the fungi tested （66.7%, 77.3%, 63.0%, 87.9%, 70.0%, 70.0% and 80.0% at 50 μg/mL）. Therefore, 13d can be used as a new lead structure for the development of antifungal agents.

Resolution of racemic R.S-α-arylethylamine by a new resolving agent (R)thiazolidine-2-thione-4-carboxylic acid

Racemic R.S-α-arylethylamine was resolved by R (-) thiazolidine-2-thione-4-carboxylic acid, a new resolving agent abbreviated as [R (-) TTCA], by which R (-) TTCA.S(-) arylethylamine salts2a-2e, [α] D 20 =-47.24° — 64.40° and optically active R(+)-a-arylethylamines3a – 3e, 74. 54%-94. 45% e, e., were obtained. Optically active S (-) -α-arylethylamines4a-4e, 72.84%-90.36% e.e., were obtained by the decomposition of2a-2e in basic solutions. The influence of substitutive group of the benzene ring on the basicity of the amino group was studied by semiempirical PM3 method. The structures of the R (-) TTCA.S (-) -α-phenylethylamine salt (2a(R-S) configuration) and R (-) TTCA-R(+)-a-phenylethylamine salt (2a(R-R) configuration) have been established by means of X-ray diffraction. They crystallize in a monoclinic system. Space group isP21. The cell constants of2a(R-S) configuration were obtained as follows: α = 1.387 8(2), b = 0.664 05(101,c = 1.580 O(2) nm; β = 90.844(10)° Z = 4; those obtained for2a(R-R) configuration were α = 1.080 6(2),b = 0.584 80(12),c = 1.2188(2) nm, β= 110.38(3)dg, V = 0.7220nm3,Z = 2. There are intermolecular hydrogen bonds in the crystals of the two kinds of configurations of the amine salt. The hydrogen bond number in the unit cell of R (-) TTCA.S (-)-α-phenylethylamine salt is twice as much as that of R (-) TTCA.R(+)-a-phenylethylamine salt.

Biosynthesis of(R)-2-hydroxy-3-phenylpropionic acid using whole recombinant Escherichia coli cells in an aqueous/n-octane biphasic system

（R）-2-hydroxy-3-phenylpropionic acid （PIP,） is an ideal antimicrobial compound with broad-spectrum activity against a wide range of Gram-positive bacteria, some Gram-negative bacteria, and fungi. We studied the bioconversion of phenylpyruvate （PPA） to PLA using whole recombinant Escherichia coli cells in a series of buffer/organic solvent systems. Octane was found to be the best organic solvent. The optimum volume ratio of the water phase to the n-octane phase, conversion temperature, substrate concentration, and cell concentration were 6：4, 40 ℃, 12.5 g/L, and 30 g/L wet cells, respectively. Under the optimized conditions, the average PLA productivity in the aqueous/ n-octane system was 30.69% higher than that in the aqueous system, and 32.31 g/L PLA was obtained with the use of a stirred reactor （2-L scale）. Taken together, our findings indicated that PLA biosynthesis was more efficient in an aqueous/n-octane biphasic system than in a monophasic aqueous system. The proposed biphasic system is an effective strategy for enhancing PLA yield and the biosynthesis of its analogues.

Crystal Structure of Isoquinoline Derivatives

The chiral compound 5H-imidazol[2,3-b]isoquinoline-l-ethanol-5-one-1,2, 3, 10b-tetrahydro- β（S）-phenyl-3（S）-phenyl was synthesized from the direct condensation of 2- cyanophenyacetonitrile with optically active （S）-（＋）-2-phenylglycinol in chlorobenzene under dry, anaerobic conditions. ZnCl2 was used as a Lewis acid catalyst in this reaction, and the structure of this compound was determined by X-ray diffraction, NMR, MS and IR. Crystal data of the title compound： C25H22N2O2, Mr = 382.45, P 21 21 21, a = 5.341（5）, b = 16.735（5）, c = 22.129（5） A, γ = 90°, V = 1978（2）A^3, Z = 4, Dc = 1.284 g/cm^3, the final R = 0.0321 for 2269 observed reflections with I 〉 2 σ（I） and Rw = 0.0771 for all data.

HPLC同时测定白及中3种成分的含量

目的：建立HPLC同时测定白及中红果酸,gymnosideⅠ,militarine 3种成分的含量。方法：采用Waters Symmetry ShieldTMRP18色谱柱（4.6 mm×250 mm,5μm）,流动相乙腈（A）-0.05%磷酸水（B）梯度洗脱（0~10 min,5%~20%A;10~35min,20%~35%A;35~50 min,35%~100%A）,流速1.0 m L·min-1,检测波长225 nm,柱温25℃。结果：3种成分均能达到基线分离,线性关系良好,加样回收率在95%~105%。结论：该方法专属性强,灵敏度高、重复性好、简单易行,可用于同时测定白及药材中红果酸,gymnosideⅠ,militarine 3种成分的含量,可为白及药材的质量控制提供依据。