Towards Diastereomeric Pure Salts with Antisolvent Methods

Chiral molecules, especially enantiomers and diastereomers of purity > 99 %, present a significant market share within the chemical, pharmaceutical, and flavor industries. Antisolvent precipitations, both batch and semicontinuous operations to serve the current trends in flow chemistry were demonstrated to be environmentally benign and efficient tools in achieving high optical purities. Although salts are known to be insoluble in supercritical CO₂, instabilities of the nascent salts were detected and applied for increasing efficiency. Diastereomeric excess values of the crystalline products exceeded 99 % in maximum of three consecutive steps both by repeated resolution with half molar equivalent of the amine to the acid and by direct recrystallization of the salts.     

药用辅料对CYP3A活性的影响及其对仿制药质量和疗效一致性评价的指导作用

药物制剂的处方和工艺是保证药物质量和疗效的基础，药用辅料是药物制剂处方的重要组成部分。部分药用辅料可影响CYP3A的活性，继而可能影响其底物在体内的代谢和生物利用度。在中国和美国，相对生物利用度是仿制药研究的关键内容。我国正在推进仿制药质量和疗效一致性评价。因此，了解药用辅料对CYP3A的影响及其对一致性评价的指导作用具有十分重要的现实意义。     

A facile and efficient method for preparation of chiral supported poly(styrene–divinylbenzene) copolymers

A new and efficient method for preparation of optically active poly(styrene–divinylbenzene) copolymers (PS-DVB) is presented here. This is carried out by Friedel–Crafts acylation reaction of chiral N-phthaloyl -leucine acid chloride with PS-DVB beads in the presence of aluminum chloride as Lewis acid catalyst and 1,2-dichloroethane as the solvent at ambient temperature. Reagents’ amounts and reaction conditions are mentioned and four samples with different amounts of functionality have been prepared. Final products were characterized by FT-IR and elemental analysis. The results obtained confirm that the above modification in preparation of chiral supported PS-DVB has been achieved well and in moderate yield.     

Separation of propranolol enantiomers through membranes based on chiral derivatized polysulfone

The characterization of new synthesized chiral polymeric membranes, based in polysulfone polymer is here reported. Polysulfone was derivatized to chiral polysulfone, by bonding covalently the chiral carrier, N-dodecyl-4(R)-hydroxy-l-proline, to the polymer matrix. Two different chiral polysulfones, referred to as CPS_A and CPS_B, have been synthesized and used in the preparation of chiral polymeric membranes. However, as a consequence of the limited CPS_B solubility, only CPS_A resulted adequate to obtain useful membranes. Therefore, various chiral polysulfone membranes containing different amounts of CPS_A in unmodified polysulfone (PS) were prepared and properly characterized by scanning electron microscopy (SEM) and by enantioselective transport experiments of racemic propranolol. Dialysis transport experiments allowed us to determine the influence of the carrier content in the membrane on the transport rate and on enantiomer separation. Membranes containing a CPS_A/PS ratio of 1:3 showed an alpha value of 1.1 at 96 h of performance. Modelling of the propranolol transport rate is also performed.     

旋波媒质基本参数的一种测试方法

本文提出了直接利用旋波材料板的Ｓ参数获得其基本参数的方法。通过自由空间测量旋波材料板的反射场和透射场，可以反演得到媒质的复介电常数、复磁导率、旋波量以及透射场的轴比和旋转角，测试程序简单，结果精度高。     

Photoswitching of Ferroelectric Liquid Crystals Using Unsymmetrical Chiral Thioindigo Dopants: Photoinduced Inversion of the Sign of Spontaneous Polarization

A new unsymmetrical chiral thioindigo dopant 6‐[(R,R)‐2,3‐difluorooct‐1‐yloxy]‐5′‐nitro‐6′‐[(R)‐2‐octyloxy]thioindigo ( 4 ) designed to photoinvert the sign of spontaneous polarization (P_S) in a ferroelectric chiral smectic C (SmC*) liquid crystal was prepared using a synthetic approach previously developed in our laboratory. In this new “ambidextrous” design, the (R)‐2‐octyloxy side‐chain is sterically coupled to the thioindigo core and induces a positive P_S, whereas the (R,R)‐2,3‐difluorooctyloxy side‐chain is decoupled from the core and induces a larger negative P_S. In the trans form, this dopant induces a negative polarization in the SmC host (+)‐4‐(4‐methylhexyloxy)phenyl 4‐decyloxybenzoate ( PhB ). Irradiation of a 1 mol‐% mixture of 4 in PhB at λ = 510 nm caused a sign inversion of P_S, from –0.88 to +0.42 nC cm^–2 at T – T_C = –5 °C, which is consistent with an increase in the polarization power of the coupled 2‐octyloxy/thioindigo unit over that of the 2,3‐difluorooctyloxy unit, due to the increase in transverse dipole moment of the thioindigo core upon trans–cis photoisomerization. The P_S sign inversion was confirmed by a surface‐stabilized ferroelectric liquid crystal photoswitching experiment. Spectroscopic measurements on films of the doped liquid crystal mixtures showed that trans–cis photoisomerization is gradually suppressed with increasing dopant mole fraction, possibly as a result of increased dopant aggregation.     

Enantioseparation of catechin and epicatechin in plant food by chiral capillary electrophoresis

The enantiomers of catechin and epicatechin were separated by chiral capillary electrophoresis using modified cyclodextrins as chiral selectors. Various conditions for the separation system were optimized, including the pH value and the concentration of the running buffer. A baseline separation of the catechin and epicatechin enantiomers could be achieved by using 0.1 mol l⁻¹ borate buffer (pH 8.5) with 12 mmol l⁻¹ (2-hydroxypropyl)-γ-cyclodextrin as chiral selector, a fused-silica capillary with 40 cm effective length (75 μm I.D.), +18 kV applied voltage, a temperature of 20 °C and direct UV detection at 280 nm. The method was applied to different plant food samples. (+)-Catechin and (−)-epicatechin could be verified as the most common flavan-3-ols. In the case of guaraná, however, we were able to identify all four enantiomers, both (+)- and (−)-catechin and (+)- and (−)-epicatechin, as naturally occurring compounds. This finding was verified by further isolation and purification of the flavan-3-ols and subsequent LC–MS analysis. This method allows for the identification of the authenticity of guaraná through the analysis of the catechin and epicatechin enantiomers, additionally to the conventional methods like HPLC.     

Random Copolymers with 2,2′-Dioxy-1,1′-biphenyl-phosphazene and Chiral 2,2′-dioxy-1,1′-binaphthylphosphazene Units Functionalized in the 6,6′-Positions with PPh<Subscript>2</Subscript> Groups as Precursors for Ru(arene) Catalysts

The chiral phosphazene copolymers {[NP(O₂C₁₂H₈)]_0.9[NP(O₂C₂₀H₁₂)]_0.1} (1) and {[NP(O₂C₁₂H₈)]_0.9[NP(O₂C₂₀H₁₀Br₂)]_0.1} _n (2) [(O₂C₁₂H₈) = 2,2′-dioxy-1,1′-biphenyl; (O₂C₂₀H₁₂) = R-2,2′-dioxy-1,1′-binaphthyl and (O₂C₂₀H₁₀Br₂) = R-6,6′-dibromo-2,2′-dioxy-1,1′-binaphthyl] were prepared by sequential substitution from [NPCl₂] _n and the corresponding dihydroxy-biphenyl or binaphthyl reagents in the presence of Cs₂CO₃ and K₂CO₃. The reaction of (2) with ^tBuLi in THF, followed by addition of PPh₂Cl and a treatment with SiHCl₃/PPh₃ to eliminate any oxidized OC₆H₄P(O)Ph₂ groups, gave the phosphine containing copolymer {[NP(O₂C₁₂H₈)]_0.9[NP(O₂C₂₀H₁₀[PPh₂]₂)]_0.1} _n (3), that was used as a chiral ligand to support [Ru(p-cymene)Cl] complexes. The resulting catalyst was active for hydrogen transfer from isopropyl alcohol to acetophenone but the placement of the Ru centers in the 6,6′-positions of the binaphthoxyphosphazene units induced no enantioselectivity. Dedicated to Professor Christopher Allen.     

Synthesis and self-assembly of comb oligomers having rigid racemic or chiral binaphthyl macrocyclic pendant groups

In this article, we described the synthesis of comb oligomers having rigid racemic or chiral binaphthyl macrocyclic pendant groups via the free radical polymerization. Oligomers obtained were well characterized by MALDI-TOF-MS, ¹H NMR, FT-IR, UV, CD and SEC. These comb oligomers having macrocyclic pendant groups showed very good solubility in common organic solvents at room temperature. Furthermore, the oligomers could self-assemble into different morphologies by dropping their THF solutions of different concentrations on the surface of water. At a relatively low concentration, the oligomers self-aggregated into hollow spheres. When the concentration was increased, the aggregates changed into solid spheres. The morphologies of the hollow or solid spheres were observed by TEM and ESEM.     

铼(Ⅶ)催化烯丙醇移位/去对称化串联反应

使用Re_2O_7和手性磷酸为共催化剂,实现了催化不对称的环己二烯酮烯丙醇移位/氧杂-Michael加成串联反应。通过这一反应,可以一步构建带有三个手性中心的环己烯酮骨架结构,为合成带有这一类骨架的天然产物和药物分子提供了高效的合成方法。同时,通过分析条件的优化,找到了合适的手性拆分条件,为光学活性环己烯酮化合物提供了分析方法。