Enantiomeric separation of 2-(phenoxy)propionate derivatives by chiral high-performance liquid chromatography

2-(Phenoxy)propionate derivatives were separated on three chiral columns, OD, OK, and chiral-2 columns. The chlorine substitution in the phenyl ring and the alcohol moiety of the ester groups of the derivatives had great influence for separation on the OD and OK columns, but little effect on the chiral-2 column.     

Chromatographic resolution of chiral intermediates in β-adrenergic blocker synthesis on chiral stationary phases

The enantiomeric purities of optically active intermediates for β-adrenergic blocking agents prepared via enzyme-assisted processes can be determined rapidly and with high accuracy using HPLC on commercially available columns with chiral supports [Chiralcel OD, OB; Chiralpak OT(+)]. The dependence of the resolution parameters on the substitution pattern of both hydroxy compounds and their esters is reported. © 1993 Wiley-Liss, Inc.     

白腐真菌Trametes sp. SQ01漆酶的新功能:转化2-羟基-6氧-6-苯基-2，4-己二烯酸

【目的】利用白腐真菌Trametes sp.SQ01漆酶转化2-羟基-6氧-6-苯基-2,4-己二烯酸(HOPDAs),可以帮助我们进一步了解漆酶新的催化特性及解决多氯联苯降解过程中HOPDAs的积累问题。【方法】利用紫外可见光谱分析法,研究了漆酶对8种不同取代基的HOPDAs的转化情况,并对漆酶的稳态动力学参数进行了测定。【结果】漆酶可以在没有任何中介物的条件下催化HOPDAs,并生成无色的物质,尤其是漆酶可以催化3,8,11-3Cl HOPDA,而这一物质几乎不能被BphD和Rhodococcus sp.R04转化。稳态动力学分析表明,在5种HOPDAs中,10-Cl HOPDA是漆酶的最适底物,其Km与HOPDA和8-Cl HOPDA相近。尽管3,10-2F HOPDA并不是漆酶的最适底物(Km=17.02μmol/L),但是它的转化效率(kcat/Km)是最高的。【结论】漆酶可以有效转化多种HOPDAs,这为多氯联苯的降解提供一种新的思路。     

2-氧代-4-苯基丁酸乙酯还原酶产生菌筛选及产酶条件

研究了利用生物催化不对称还原的方法制备(R)-2-羟基-4-苯基丁酸乙酯[(R)-HPBE]。以2-氧代-4-苯基丁酸乙酯(OPBE)为底物,通过对实验室保藏菌株进行筛选,得到一株产物立体选择性较高的菌株G2ndida krusei SW2026,并对其发酵产酶条件进行研究。其最适的发酵培养基组成为4.5%葡萄糖,3%蛋白胨,1.5%牛肉膏,0.05%Mn~(2+);适宜的产酶发酵条件为初始pH 6.0,温度28℃,摇床转速180 r/min,发酵周期48 h。将此条件下发酵培养的菌体用于OPBE的不对称还原反应,产物(R)-HPBE的对映体过量值(e.e.)可达97.33%,产率最高达到72.54%。     

Sugar Composition of Cell Wall Polysaccharides of Suspension-cultured Tobacco Cells

Neutral sugar composition of cell walls of suspension-cultured tobacco cells was examined with the advance of culture age by an anion-exchange chromatography. Isolated cell walls gave on hydrolysis the following sugars: 2% of l-rhamnose, 6% of d-mannose, 26% of l-arabinose, 13% of d-galactose, 8% of d-xylose and 47% of d-glucose as neutral sugars. Little changes in composition of cell wall polysaccharides were recognized with the advance of culture age. Sugar composition of the extra-cellular polysaccharides was similar to that of hemicellulose fraction from cell walls. Pectinic acid gave on hydrolysis 2-O-(α-d-galactopyranosyluronic acid)-l-rhamnose, d-galacturonic acid and its oligosaccharides.     

A homogeneous enzyme immunoassay with avidin-ligand conjugate as the enzyme-modulator

A homogeneous enzyme immunoassay (EIA) based on the immunomodulation of an avidin-ligand conjugate and the inhibition of pyruvate carboxylase is described. The conjugation of the ligand, 5,5-diphenylhydantoin (DPH), to avidin does not affect avidin's capacity to bind biotin or inhibit pyruvate carboxylase. The DPH-avidin conjugate and free DPH were shown to compete for a limited number of antibody sites. The interaction of anti-DPH with the DPH-avidin conjugate sterically inhibited enzyme inactivation. Enzyme activity was correlated with DPH concentrations in the therapeutic range found in serum.     

Chiral-at-metal tetrahydrosalen complexes of resolved titanium(IV) sec-butoxides: Ligand wrapping and multiple asymmetric catalytic induction

The reaction of the racemic and resolved tetrahydrosalen derivative LH₂ (LH₂ = N,N’-bis(3,5-dichloro-2-hydroxybenzyl)-trans-1,2-diaminocyclohexane) with the resolved titanium(IV) sec-butoxides Ti(O^R-2Bu)₄ or Ti(O^S-2Bu)₄ yielded a series of four compounds, LTi(O²Bu)₂ (1-4), which have been characterized by IR, elemental analysis, ¹H and ¹³C NMR and X-ray crystallography. X-ray crystallography revealed the co-crystallization of two pseudo-C₂-symmetric products from racemic LH₂, whereas a perfect chiral induction of the ligand to the metal occurred when resolved (R,R)-LH₂ was used, resulting in a Δ fac-fac wrapping mode of the tetradentate ligand about the titanium center. Ab initio electronic structure calculations (DFT) are in agreement that the lowest energy isomer is that which is experimentally observed. Catalysis screenings show that Ti(O^S-2Bu)₄, in conjunction with (R,R)-LH₂, forms a matched pair that catalyzes the addition of dimethyl zinc to benzaldehyde with higher enantioselectivity than that observed for resolved (R,R)-LH₂ with Ti(O^R-2Bu)₄ or achiral Ti(OⁱPr)₄. Increasing the temperature of the system results in slightly increased enantiomeric excess.     

Effects of delayed and extended antioxidant treatment on acute acoustic trauma

Abstract

Objective: Hair cell death caused by acute acoustic trauma (AAT) reaches a secondary maximum at 7–10 days after noise exposure due to a second oxidative stress. Therefore, this study tested the effects of a combination of hydroxylated alpha-phenyl-tert-butylnitrone (4-OHPBN), N-acetyl-L-cysteine (NAC) and acetyl-L-carnitine (ALCAR) on AAT when the duration of treatment was extended over the period of 7–10 days after noise exposure as well as when the initial treatment was delayed 24 to 48 h after noise exposure. Methods: Thirty chinchilla were exposed to a 105 dB octave-band noise centred at 4 kHz for 6 h and received the following treatments: (1) noise + saline (2–5) 4-OHPBN (20 mg/kg) + NAC (50 mg/kg) + ALCAR (20 mg/kg) intraperitoneally injected beginning 24 or 48 h after noise exposure twice daily for the next 2, 8 or 9 days. Auditory brainstem response (ABR) threshold shifts, outer hair cell (OHC) counts and organ of Corti immunohistochemistry were analyzed. Results: The combination administration decreased ABR threshold shifts, inhibited OHC loss and reduced 4-hydroxynonenal (4-HNE) immunostaining. Significant decreases in the threshold shifts and reduction in OHC loss were observed with a shorter delay before starting treatment (24 h) and longer duration (9 days) treatment. Conclusions: These results demonstrate that the administration of antioxidant drugs extended up to 10 days after noise exposure can effectively treat AAT in a chinchilla model. This may provide significant and potentially clinically important information about the effective therapeutic window for AAT treatment.     

Potential Inhibitors of Angiogenesis. Part II: 3-(Azolylmethylene)-2,3-dihydrobenzo[b]furan-2-ones

The synthesis and pharmacological evaluation of new 3-(imidazol-4(5)-ylmethylene)-2,3-dihydrobenzo[b]furan-2-ones 8-10 and 3-(3,5-dimethylpyrrol-2-ylmethylene)-2,3-dihydrobenzo[b]furan-2-one 11, analogues of SU-5416, as potential inhibitors of angiogenesis, are reported. Compounds 8 and 11 were prepared by a Knoevenagel reaction starting from 2-hydroxyphenylacetic acid 2 and 4-formylimidazole 5 or 2-formyl-3,5-dimethylpyrrole 7, followed by acid-catalysed cyclodehydration. For compounds 9 and 10, an alternative method was used; it consisted in carrying out the Knoevenagel reaction with the 2,3-dihydrobenzo[b]furan-2-ones 3 and 4. The antiangiogenic activity of these compounds was evaluated in the three-dimensional in vitro rat aortic rings test at 1 μM. At this concentration, compound 11 induced a decrease of angiogenesis comparable to that observed with SU-5416; the vascular density index at 1 μM of 11 and SU-5416 were 30±10 and 22±4% of control, respectively.     

The synthesis and spectroscopic analysis of the neurotoxic prion peptide 106-126: Comparative use of manual Boc and Fmoc chemistry

A peptide corresponding to residues 106-126 of the human prion protein (PrP) possesses the neurotoxic and amyloidogenic properties of the infectious form of the parental protein. This peptide is now identified as a 'difficult sequence' and synthesis using conventional manual Fmoc chemistry was unsuccessful with acylation terminating at a central core of hydrophobic amino acids. The use of tetramethylfluoroformamidinium hexafluorophosphate and 1-methyl-2- pyrrolidone as anti-aggregatory agents in the coupling steps improved the synthesis but still resulted in an incomplete peptide. The incorporation of N-(2-hydroxy-4-methoxybenzyl) protection at glycine residues 119 and 124 enabled synthesis of the full length peptide in low yield. Synthesis using Boc chemistry with in situ neutralisation gave the full length peptide in high yield.     

Microbial Asymmetric Reduction. Preparation of Optically Active Methyl trans-3-(4-Methoxyphenyl)Glycidates

As a result of screening of microorganisms, Mucor ambiguus IFO 6742 was found to reduce methyl 2-chloro-3-(4-methoxyphenyl)-3-oxopropionate (2) to give methyl (2S,3R)-2-chloro-3-hydroxy-3-(4-methoxyphenyl)propionate [(2S,3R)-3] in good yield with high enantioselectivity. The resulting (2S, 3R)-3 was converted into methyl (2S,3R)-3-(4-methoxyphenyl)glycidate [(2S,3R)-4] by treatment with sodium methoxide. On the other hand, its enantiomer, (2R,3S)-4 was obtained by the Mitsunobu esterification of (2S,3R)-3 and subsequent treatment with sodium methoxide. Also (2R,3S)-4 was obtained by the treatment of (2RS,3S)-3, which was obtained from 2 by Trichoderma viride OUT 4642, with sodium methoxide.     

月腺大戟根中有效成分乙素和丙素的结构研究

本文主要报道从月腺大戟(Euphorbia ebracteolata Hayata)根中分离出的对结核菌有抑制作用的晶Ⅵ(乙素)和晶Ⅶ(丙素)的化学结构。经化学反应及光谱鉴定,确定晶Ⅵ为2,4-二羟基-6-甲氧基-3-甲基-苯乙酮,晶Ⅶ为2-羟基-6-甲氧基-3-甲基-1-苯乙酮-4-6-葡萄糖甙。乙素为首次分离的天然产物,丙素为新的化合物。该植物提取物对结核病有明显疗效。