New particle-loaded monoliths for chiral capillary electrochromatographic separation

Fritless particle-loaded monoliths for chiral capillary electrochromatographic (CEC) separation were prepared. Silica particles containing a chiral selector are suspended in a monomer solution, which is drawn into the capillary followed by in situ polymerization. Thereby the silica-based particles containing the chiral selector are embedded in a nonchiral continuous bed. This kind of chiral stationary phase is inexpensive, easy, and reproducible to prepare and circumvents the preparation of frits. As a model, teicoplanin aglycone as chiral selector bonded to 3 microm silica particles was used. The applicability of this approach is demonstrated by means of the chiral separation of aliphatic and aromatic amino acids and dipeptides. As a further application, the chiral selector ristocetin A bonded to 3 microm silica particles was used for the enantiomeric separation of chiral alpha-hydroxy acids. Since alpha-hydroxy acids migrate toward the anode, a cationic charge-providing agent was copolymerized with the matrix. This served to reverse the direction of the electroosmatic flow (EOF).     

New Chiral Macrocyclic Compounds from D-Mannitol

We have recently reported the synthesis of new chiral macrocyclic polyhydroxyethers by reduction of cyclodextrins 1. These compounds display appreciable conformational freedom in solution as it occurs with the ionophores. Our chiral macrocycles may be considered as built by units of alditol (1 → 4) alditols. Such units, conveniently substituted, prepared by us by reduction of disaccharide derivatives2, are possible synthons for the synthesis of other macrocyclic polyhydroxyethers in which the nature and number of alditol (1 → n) alditol components can be varied at will. We are interested in the preparation and the structural studies of these type of receptors since the synthesis of new chiral macrocycles is a topic of interest and the building of chiral cavities may be of importance in the study of host-guest interactions. We now report on the preparation, from D-mannitol, a readily available starting material with C₂symmetry, and tetraethylene glycol, of the chiral macrocycles 1, 2, and 3, as model compounds in exploring the synthesis of more complex macrocyclic polyhydroxyethers derived from alditol (1 → n) alditol. Other macrocyclic compounds from D mannitol have been previously synthesised.     

New pyrimidino-crown ether ligands

Eight new macrocyclic ligands containing the pyrimidine subcyclic unit ( 3-10 , Figure 1) have been prepared. Two of these new crown ethers are chiral. Pyrimidino-crowns 3-8 were prepared by treating the di-tosylate derivative of the appropriate oligoethylene glycol with 4-methoxy-5-raethyl-2,6-pyrimidinedimeth-anol in basic conditions. The yields were in the 30-50% range giving the crowns as viscous oils. Chiral dimethyl-substituted pyrimidino-crown 9 was prepared from 4-methoxy-5-methyl-2,6-pyrimidinedimethyl di-tosylate and chiral dimethyl-substituted tetraethylene glycol. Treatment of dimethyl 4-methoxy-5-methyl-2,6-pyrimidinedicarboxylate with the diamine derivative of chiral dibenzyl-substituted tetraethylene glycol gave the chiral dibenzyl-substituted pyrimidino-crown diamide 10. Starting 4-methoxy-5-methyl-2,6-pyrimidinedi-methanol was prepared by a six step process from acetamidine hydrochloride and diethyl oxalpropionate.     

New approaches to chiral discrimination in coupling between molecules

Results in the coupling of chiral molecules are reviewed from elementary points of view and some new results are given. We show that interactions between chiral molecules can be treated by using molecular quantum electrodynamics in electric and magnetic dipole approximation in ways different from standard diagrammatic perturbation theory. The interactions are the dispersive coupling of ground-state chiral molecules and excitation transfer, with emphasis on chiral discrimination. For ground-state molecules the coupling is dealt with first by calculating the coupling, at all separation distances, of electric and magnetic dipoles induced in the two molecules by fluctuations in the vacuum radiation field. The second method is the response by one chiral molecule to the field generated by the other. Excitation transfer is treated as the response by the accepting ground-state molecule to the dipole field of the donor. A novel variant in finding the rate of excitation transfer is by using Poynting's theorem. Received: 17 June 1998 / Accepted: 6 October 1998 / Published online: 16 March 1999     

New chiral ionic liquids based on imidazolinium salts

The preparation and application of a new series of chiral ionic liquids are described. The salts are based on imidazolinium cations. Some of the cations also incorporated an axial chirality at the C(2) position next to the central chirality. These cations display a very high rotational barrier along the arene–imidazolinium axis. Furthermore, an analogue with a chiral anion was prepared. The salts have low melting points. Their potential as solvents and as chiral shift reagents was explored, resulting for the first time in an example of a chiral ionic liquid as a shift reagent for a neutral compound.     

金属催化的不对称氢化反应研究进展与展望

手性过渡金属络合物催化的不对称氢化反应是合成光学活性化合物的重要方法. 本文从手性配体及手性催化剂、不对称催化新反应、新方法和新策略三个方面简要评述新世纪以来过渡金属催化的不对称氢化反应研究领域的新进展. 从新世纪初至今, 手性单磷配体得到了复兴, 出现了如MonoPhos、SiPhos、DpenPhos等高效单齿亚磷酰胺酯配体; 磷原子手性(P-手性)配体也得到了快速发展, 如BenzP*、ZhanPhos、TriFer等已成为新的高效手性双膦配体; 螺环骨架手性配体成为新世纪手性配体设计合成的亮点, 除了SiPhos、SIPHOX、SpinPHOX等高效手性螺环配体外, 手性螺环吡啶胺基磷配体SpiroPAP的铱催化剂成为目前最高效的分子催化剂. 不对称催化氢化新反应研究也取得了突破, 如非保护烯胺、杂芳环化合物及N-H亚胺的氢化等反应都实现了高对映选择性. 自组装手性催化剂、树枝状手性催化剂、铁磁性纳米负载的可回收手性催化剂, 以及“混合”配体手性催化剂等新方法和新策略也在不对称催化氢化反应中得到了应用. 然而, 手性过渡金属络合物催化的不对称氢化研究仍然充满挑战, 也期待新的突破.     

Enantioselective Alkynylation of Benzaldehyde Catalyzed by New Chiral Lewis Acid Ligand: Zinc-Amide Complex

The enantioselective alkynylzinc addition to aldehydes is very useful for the synthesis of chiral propargyl alcohols which are important versatile building blocks of many biologically active compounds and natural products1. A series of chiral oxazolidines were conveniently synthesized from amino acids in three steps with good yields. The use of chiral Lewis acid ligand: zinc-amide complex in situ generated from this oxazolidine with alkylzinc as chiral catalysts for the enantioselective alkyny…     

Peptide Deravatives as New Chiral Ligands for Enantioselective Phenylacetylene Addition to Aldehydes

The asymmetric addition of alkynylzinc to aldehydes is an important method of synthesizing chiral propargyl alcohols, which are important precursors to many chiral organic compounds. Recently, many significant chiral ligands in this area have been disclosed.[1] Use of a short peptide as a catalyst would allow expansion beyond the (still uncharted) repertoire of single amino acids, while conserving the advantages of a small molecule catalyst. To the best of our knowledge,no results of peptide derivatives as chiral ligands in this reaction has been disclosed to date.[2] Herein, we report the initial results of peptide derivatives, which have been used directly as a chiral ligand in this reaction (Scheme 1).     

New chiral building blocks of β-peptoid analogs

The synthesis of chiral functionalized β-amino esters via the hydride reductive amination of chiral allenes was explored. These compounds can be regarded as β-peptoids building blocks bearing a chiral side chain at the nitrogen and at the same time retaining the β-amino acid side chain. β-Enamino esters were obtained from the nucleophilic addition of α-amino esters (l-Ala, d-Ala, l-Phe, l-Leu, l-Trp and d-Trp methyl esters) to 2,3-allenoates bearing a chiral auxiliary, which determines the stereochemistry outcome of the subsequent reduction reaction. It was also demonstrated that in the reduction of β-enamino esters derived from l-Pro and d-Pro methyl esters the chirality of the new chiral center is controlled by the α-amino ester moiety.     

化学拆分的新方法研究

主要介绍了近年来发展起来的两种化学拆分新方法,包括拆分和组合拆分;并简要论述了化学拆分中的手性识别现象,以及化学拆分方法在手性药物制备中的应用。     

Functionalized Chiral Ionic Liquids: A New Type of Asymmetric Organocatalysts and Nonclassical Chiral Ligands

By judiciously anchoring functional groups onto chiral ionic liquids, functionalized chiral ionic liquids (FCILs) are emerging as a new type of asymmetric organocatalysts and nonclassical chiral ligands. This Focus Review highlights the applications of FCILs from the viewpoint of asymmetric catalysis. We focus mainly on the de novo designed and synthesized FCILs which likely still maintain the typical ionic liquids properties, and in a few cases relevant ionic liquid immobilized chiral catalysts are briefly discussed.     

双氨基酸手性五配位氢膦烷化学新进展

本文关注了氨基酸手性五配位磷化学的新进展,结合本实验室对五配位磷的长期研究工作,对一类双氨基酸手性五配位磷化合物的结构进行了系统总结.确定该系列化合物中心磷原子属于三角双锥构型,H原子和两个N原子在平伏键,两个O原子在直立键.在此基础上,借鉴配位化合物的命名规则,对其绝对构型进行命名,并通过固体CD光谱以及1H NMR对该系列化合物的绝对构型进行关联.1H-1H COSY信号的差异表明,此类化合物还存在着特殊的4JH-C-N-P-H耦合相互作用.     

New 2,2'-substituted 4,4'-dimethoxy-6,6'-dimethyl[1,1'-biphenyls], inducing a strong helical twisting power in liquid crystals

Based on the stabilisation of the molecular motion by the chiral residue, novel optically active biphenylic chiral dopants for nematic liquid crystals were developed. This molecular congestion was obtained by introducing mesogenic residues on the 2,2'-positions of the chiral biphenyl; this led to a novel molecular architecture that was found to be efficient. The synthesised optically active biphenyls were characterised with very short cholesteric pitches when used as chiral dopants in nematic liquid crystals. The synthesis of the enatiomerically pure biphenyl dopants and their preliminary physicochemical characterisations are described.     

New cleft-like molecules and macrocycles from phosphonate substituted spirobisindanol

We have synthetized medium-sized cyclophanes and macrocycles containing phosphonic groups, directly linked to the aromatic rings of the phanes or as pendant arms,for use as specific receptors for the selective complexation of neutral guests or for complexing lanthanides, as luminescent sensors and for diagnostic bioassays in medicine.Furthermore, because it would be of great interest for biochemistry as well as for pharmacological studies to dispose of preorganized rigid chiral hosts for biorelevant molecules we designed inter alia, some new chiral macrocycles capable of a triple binding mode and we used them for constructing macrocycles that could also be of interest for chiral recognition and chiral separations. Thus, in this paper we shall review the salient aspects of some macrocycles synthetized in our laboratory, all possessing the phosphonate moiety and a spirobisindanol scaffold and able to act as complexing agents for cations and organic substrates. In particular, we shall describe their NMR characterization, their stereochemistry in solution and in the solid state, and their use as chiral receptors for biorelevant molecules. Chiral HPLC resolution of some of them is also reported.     

New Chiral Calixarene Derivatives： Syntheses and Their Chiral Recognition Toward Amino Acids by UV-Vis Spectroscopy

Three novel types of chiral calixarene derivatives 5, 8, and 10 were designed and synthesized by introducing chiral units to parent calixarenes. Their chiralities were confirmed by rotational analysis. Chiral recognition properties of these host compounds towards L- and D-threonine were studied by UV-Vis spectroscopy. The results indicated that calixarene derivatives 5 and 8 exhibited good chiral recognition capabilities toward L- or D-threonine. Although calixarene derivative 10 had no evident chiral recognition ability, the supramolecules of calixarene derivative 10 with L- or D-threonine showed a hypochromic effect or hyperchromic effect respectively. Therefore, calixarene derivative 10 might serve as a good chiral UV-indicator.     

Synthesis of New Phase-Transfer Catalysts and Their Application in Asymmetric Alkylation

Despite phase transfer catalysis (PTC) is an important and useful method in organic synthesis, asymmetric synthesis using chiral phase-transfer catalyst has not been well documented and limited number of chiral phase-transfer catalyst have been developed^[1].In 1989,O'Donnell published his pioneering work in the asymmetric synthesis of α-amino acids by enantioselective alkylation of a prochiral protected glycine derivative using chiral phase-transfer catalyst^[2]. Since then, several groups reported their improvements on enantioselectivity and applicability on this useful synthetic reaction^[3,4]. However, almost all of the chiral phase-transfer catalysts reported so far are the derivatives of cinchona^[5]. In this presentation, we wish to describe the design and synthesis of a new type of chiral phase-transfer catalyst based on the camphor and its application in asymmetric alkylation of tert-bntyl glycinate-benzophenone Schiff base.     

New types of multifunctional liquid crystalline photochromic copolymers for optical data recording and storage

A new family of multifunctional chiral‐photochromic liquid crystalline (LC) copolymers containing mesogenic, chiral and photoactive groups were synthesized. The new principles of photo‐regulation of the helical supramolecular structure and optical properties of the binary and ternary chiral‐photochromic LC polymers based on the change of helical twisting power of the chiral‐photochromic monomer units, the dual photochromism and photochemical spectral gap burning were developed. It was shown, that the introduction of small amount of low‐molar‐mass chiral‐photochromic dopants in chiral LC copolymers having different helix signs followed by light irradiation permits one to twist or untwist the helical supramolecular structure. The synthesized polymers are shown to be promising candidates for colour data recording and storage.     

Carbohydrates as Chiral Auxiliaries in Stereoselective Synthesis. New Synthetic Methods (90)

Carbohydrates are inexpensive natural products in which numerous functional groups and stereogenic centers are combined in one molecule. By directed regio-and stereoselective formation of derivatives they can be converted into efficient chiral auxiliaries for controlling asymmetric syntheses. Stereoelectronic effects and pre-orientation of the reactive and shielding groups through formation of complexes can often be used for effective diastereofacial differentiation. In aldol reactions and alkylations on carbohydrate ester enolates intramolecular complexation promotes simultaneous elimination with formation of ketene. The steric, stereoelectronic, and coordinating properties of carbohydrate templates can also be used selectively to attain high levels of asymmetric induction in processes such as Diels–Alder reactions, hetero-Diels–Alder reactions, [2 + 2] cycloadditions, cyclopropanations, and Michael additions. It was possible with bicyclic, strongly stereodifferentiating carbohydrate auxiliaries to achieve a diastereoselective synthesis of carboxylic acid derivatives branched in the β position by a new 1,4-addition of alkylaluminum halides to α,β-unsaturated N-acylurethanes, in which methylaluminum halides and higher alkyl- or arylaluminum compounds behave mechanistically in a strikingly different manners. As complex ligands in chiral reagents and promoters, carbohydrates allow highly stereoselective reductions and aldol reactions that lead, amongst others, to chiral alcohols and β-hydroxy-α-amino acids in excellent enantiomeric excesses. Glycosylamines offer the possibility of versatile stereoselective applications: in the presence of Lewis acids the corresponding aldimines permit high-yielding syntheses of enantiomerically pure α-amino acids by Strecker and Ugi reactions, controlled by steric and stereoelectronic effects and by complex formation. They can be used with equal efficiency for asymmetric syntheses of chiral homoallylamines and for asymmetric Mannich syntheses of β-amino acids and chiral heterocycles, for example alkaloids.     

New Chiral Metal Cluster Systems for Catalytic Asymmetric Syntheses of Chiral Alcohols

The efficient chiral Ru3(CO)12 systems were prepared in situ from Ru3(CO)12 and various chiral diiminoor diamino-diphosphine tetradentate ligands. The systems have been used for the asymmetric transfer hydrogenation of propiophenone in 2-propanol, leading to 1-phenyl-1-propanol in a 98% yield and 96% e.e. The IR study suggests that the carbonyl hydride anion [HRu3(CO)11]^- most probably exists as a principal species under the reaction conditions. The high chiral efficiency may be due to the synergetic effect produced by the neighboring ruthenium atoms and a special chiral micro-environment involving the polydentate ligand and the Ru3 framework.     

Pillararene Host–Guest Complexation Induced Chirality Amplification: A New Way to Detect Cryptochiral Compounds

The contradiction between the rising demands of optical chirality sensing and the failure in chiral detection of cryptochiral compounds encourages researchers to find new methods for chirality amplification. Inspired by planar chirality and the host–guest recognition of pillararenes, we establish a new concept for amplifying CD signals of cryptochiral molecules by pillararene host–guest complexation induced chirality amplification. The planar chirality of pillararenes is induced and stabilized in the presence of the chiral guest, which makes the cryptochiral molecule detectable by CD spectroscopy. Several chiral guests are selected in these experiments and the mechanism of chiral amplification is studied with a non‐rotatable pillararene derivative and density functional theory calculations. We believe this work affords deeper understanding of chirality and provides a new perspective for chiral sensing.