手性不对称脲氨基醇的合成

L-氨基酸甲酯盐酸盐与三光气和苯胺反应合成了手性不对称脲氨基酸甲酯(2),2经NaBH4还原得到8个手性不对称脲氨基醇,其结构经1H NMR,IR和MS确证。     

Synthesis of chiral ionic liquids from natural amino acids

For the first time, chiral imidazolium ionic liquids containing one chiral carbon (10a-c) were synthesized from the natural amino acids by a simple and straightforward procedure. The characteristics of the chiral ILs are very similar to the popular ionic liquids.     

SiO2固载咪唑基手性硫醚钯(ll)催化剂的合成及其在Suzuki反应中的应用

以L-缬氨酸、L-亮氨酸和L-苯丙氨酸为原料合成了未见报道的4种咪唑基手性硫醚化合物,并将咪唑基硫醚固载到SiO2上制备了二氧化硅固载咪唑基手性硫醚配体,用元素分析、热重等手段进行了表征;进而与PdCl2反应得到二氧化硅固载咪唑基手性硫醚-钯(Ⅱ)催化剂,用XPS等方法对其进行了表征.考察了该催化剂在Suzuki反应中的催化性能.结果表明,在以溴苯与苯硼酸为底物的Suzuki反应中,该催化剂用量为底物的0.75％、反应时间为5h、温度为80℃时,溴苯的转化率可达95％.     

新型酯键型鹅去氧胆酸分子钳的设计合成

以鹅去氧胆酸为隔离基、芳香族化合物为手臂设计合成了一类新型的分子钳, 其结构经¹H NMR, IR, MS和元素分析确证, 并且考察了其对D/L-氨基酸甲酯的对映选择性识别性能. 初步的结果表明, 这类手性分子钳对D-氨基酸甲酯有较好的识别性能.     

Imidazole-based potential Bi- and tridentate nitrogen ligands: synthesis, characterization and application in asymmetric catalysis

Twelve new imidazole-based potential bi- and tridentate ligands were synthesized and characterized. Whereas in the first series the alpha-amino acid and imidazole moieties were linked by an amino bond, in the second series the tridentate ligands, containing two imidazole groups, were separated by an amide bond. The first series was obtained by the reductive amination of 2-phenylimidazole-4-carboxaldehyde with alpha-amino acid esters. The tridentate ligands were prepared from 2-phenylimidazole-4-carboxylic acid and chiral amines. In the Henry reaction, the amines were revealed as a more reactive species than the less nucleophilic amides, however the enantiomeric excesses were generally poor.     

α-猪去氧胆酸类分子钳的设计合成

以α-猪去氧胆酸为隔离基，芳香族化合物为手臂设计合成了一类新型的酯键 型分子钳，结构均经^1H NMR，IR,MS及元素分析所确证，并且考察了其对芳香胺类 化合物和D／L-氨基酸甲酯的识别性能．初步研究结果表明，这类分子钳受体不但 对中性小分子具有识别性能，而且对D／L-氨基酸甲酯具有对映选择性识别性能．     

Facile synthesis of chiral <Emphasis Type="Italic">N</Emphasis>-glycosylated amino acids

Five designed chiral glycosylated amino acids have been synthesized for the first time by coupling of 1,3,4,6-tetra-O-acetyl-β-D-glucosamine sulfate (2), previously prepared by direct acetylation of D-glucosamine hydrochloride with acetic anhydride, with chiral Fmoc-protected amino acids and DIC, HOBt, and DIEA under mild conditions. The structures of these new compounds were characterized by IR, ¹H NMR, and ¹³C NMR spectroscopy and ESI MS.     

Click chemistry inspired synthesis of ferrocene amino acids and other derivatives

This work reports the synthesis of a wide range of ferrocenyl-amino acids and other derivatives in excellent yield. Diverse amino acid containing azides were synthesized and ligated to ferrocene employing click reaction to access ferrocenyl amino acids. Chiral alcohols, esters, diols, amines containing azido group were tagged to ferrocene via click reaction to generate ferrocene derived chiral derivatives. A novel strategy for direct incorporation of ferrocene into a peptide and a new route to 1, 1′disubstituted ferrocene amino acid derivative are reported.     

单手性臂脱氧胆酸分子裂缝的设计与微波合成

以脱氧胆酸甲酯为隔离基 ,3位构建为非手性单元 ,在 12位引入手性单元 ,合成具有不同手性中心和裂穴的新型单手性臂分子裂缝受体 .结构均经1 HNMR ,IR ,MS及元素分析所确证 ,并且考察了其对中性小分子和D/L 氨基酸甲酯的识别性能 .初步研究表明 ,这类裂缝型受体不仅对中性小分子具有优良的识别性能 ,而且对D/L 氨基酸甲酯具有良好的手性识别能力 .     

Enantiomeric recognition of amino acids by amphiphilic crown ethers in Langmuir monolayers

Four new chiral, amphiphilic crown ethers differing by the hydrophobic tailgroups were synthesized, and their capacity to recognize enantiomeric amino acids was examined using Langmuir films. Surface pressure and surface potential measurements performed on the subphases containing L or D enantiomers of alanine, valine, phenylglycine, and tryptophane indicate that the crown ethers forming the monolayer interact with the amino acids. The effects observed are ascribed to the formation of host-guest complexes. The differences in the magnitude of the effects measured show that the crown ethers are capable of discriminating between different amino acids as well as the enantiomers. Our results demonstrate that the structure of the monolayer plays a decisive role in the molecular recognition process including chiral recognition.     

Alternative heterocycles for DNA recognition: the benzimidazole/imidazole pair

Boc-protected benzimidazole-pyrrole, benzimidazole-imidazole, and benzimidazole-methoxypyrrole amino acids were synthesized and incorporated into DNA binding polyamides, comprised of N-methyl pyrrole and N-methyl imidazole amino acids, by means of solid-phase synthesis on an oxime resin. These hairpin polyamides were designed to determine the DNA recognition profile of a side-by-side benzimidazole/imidazole pair for the designated six base pair recognition sequence. Equilibrium association constants of the polyamide-DNA complexes were determined at two of the six base pair positions of the recognition sequence by quantitative DNase I footprinting titrations on DNA fragments each containing matched and single base pair mismatched binding sites. The results indicate that the benzimidazole-heterocycle building blocks can replace pyrrole-pyrrole, pyrrole-imidazole, and pyrrole-hydroxypyrrole constructs while retaining relative site specifities and subnanomolar match site affinities. The benzimidazole-containing hairpin polyamides represent a novel class of DNA binding ligands featuring tunable target recognition sequences combined with the favorable properties of the benzimidazole type DNA minor groove binders.     

Chiral capillary electrophoresis-mass spectrometry of amino acids in foods

In this work, the development of a new chiral capillary electrophoresis-mass spectrometry (CE-MS) method to separate D- and L-amino acids is shown. On-line coupling between CE and MS is established through an electrospray-coaxial sheath flow interface. Enantiomer separation is achieved by using a cheap, nonvolatile, chiral selector as beta-cyclodextrin in the background electrolyte (BGE) together with a physically coated capillary that is aimed to prevent contamination of the electrospray. The capillary coating is simple and easy to obtain as it only requires flushing of the capillary with a polymer aqueous solution for 3 min. Optimization of CE parameters (pH of BGE, type and concentration of chiral selector, and capillary inner diameter) and electrospray-MS parameters (nature and flow rate of the sheath liquid, nebulizer pressure) is carried out. Two different derivatization protocols of amino acids using dansyl chloride (DNS) and fluorescein isothiocyanate (FITC) are compared in terms of MS sensitivity and chiral resolution. Under optimum CE-MS conditions it is observed that the MS sensitivity obtained for FITC- and DNS-amino acids is similar (with limit of detection (LOD) in the microM range, corresponding to amounts injected in the fmol range) while chiral resolution is better for FITC-amino acids. The optimized method is demonstrated to provide the simultaneous analysis of 15 selected amino acids (i.e., FITC-D/L-Asp, -Glu, -Ser, -Asn, -Ala, -Pro, -Arg, and FITC-gamma-aminobutyric acid (GABA) in a single chiral CE-MS run, corresponding to the main amino acids that can be found in orange. Moreover, as a result of the high resolution achieved, it is possible to detect down to 2% of D-Asp in the presence of 98% of L-Asp. The good possibilities of chiral CE-MS in food analysis are corroborated through the detection of the main amino acids in a commercial orange juice (i.e., FITC-L-Asp, -Glu, -Ser, -Asn, -Pro, -Arg, and the nonchiral FITC-GABA) as well as the determination of the fraudulent addition of synthetic amino acids (containing D- and L-forms) to a fresh orange juice.     

Synthesis of novel non-proteinogenic α-amino acids with charged imidazolium fragment in the side chain

Zwitterionic imidazolium and benzimidazolium salts bearing chiral amino acid moiety were synthesized using chiral Ni^II complexes. Different N-derivatives of the synthesized enantiomerically pure amino acids were prepared; their zwitterionic structures were confirmed by X-ray analysis.     

Synthesis of noval chiral tridentate amino alcohols as chiral solvating agents under ball-milling conditions

A new family of chiral solvating agents based on chiral didentate amino alcohols and chloromethyl pyridine derivatives were synthesized by ball milling in solvent free condition. The new chiral tridentate amino alcohols were tested as chiral NMR solvating agents for the Ts-derivatives of amino acids, other several acids and pyrazole drugs. For the Ts-derivatives of amino acids studied herein, chiral tridentate amino alcohol 3a could be used for the assignment of the absolute configurations of their racemes through the chemical shift non-equivalences of their CH₃ (Ts) protons with certain confidence.     

L-亮氨酸衍生物手性氨基醇的合成与应用

以N,N-二甲基苯胺为原料,经对位溴化、邻位甲酰化得到5-溴-2-(二甲氨基)苯甲醛;L-亮氨酸经酯化、格氏反应得到二齿手性氨基醇;将5-溴-2-(二甲氨基)苯甲醛与上述氨基醇经缩合、还原得到三齿手性氨基醇;产物经红外光谱(IR)、质谱(MS)及核磁共振氢谱(1H-NMR)表征,考察了二齿手性氨基醇和三齿手性氨基醇作为...     

Synthesis of Histidine‐Containing Oligopeptides via Histidine‐Promoted Peptide Ligation

Histidine‐containing peptides are valuable therapeutic agents for a treatment of neurodegenerative diseases. However, the synthesis of histidine‐containing peptides is not trivial due to the potential of imidazole sidechain of histidine to act as a nucleophile if unprotected. A peptide ligation method utilizing the imidazole sidechain of histidine has been developed. The key imidazolate intermediate that acts as an internal acyl transfer catalyst during ligation is generated by deprotonation. Transesterification with amino acids or peptides tethered with C‐terminal thioester followed by N→N acyl shifts led to the final ligated products. A range of histidine‐containing dipeptides could be synthesized in moderate to good yields via this method without protecting the imidazole sidechain. The protocol was further extended to tripeptide synthesis via a long‐range N→N acyl transfer, and tetrapeptide synthesis.     

微波促进一锅法合成氨基甲酸酯型α-猪去氧胆酸分子钳

在微波辐射条件下, 以α-猪去氧胆酸为隔离基, 通过三光气桥连各种芳香胺, 以很好的产率合成了一系列新的手性分子钳, 其结构经¹H NMR, IR, MS和元素分析确证, 并且考察了其对中性分子和D/L-氨基酸甲酯的识别性能. 实验结果表明, 这类分子钳人工受体不仅对中性有机小分子具有优良的识别性能, 而且对D/L-氨基酸甲酯亦具有良好的对映选择性识别能力.     

Application of DEPBT on the Synthesis of the Protected Dipeptides Containing Histidine with Unprotected Imidazole Group by Solution Method

3- (Diethoxyphosphoryloxy)- 1,2,3-benzotriazln-4 (3H)-one (DE-PBT) was an organophosphorus coupling reagent developed by our group. It was an effective coupling reagent for the synthesis of protected peptides containing Tyr, Ser and Thr with unprotected hydroxy group on their side chain. The further study of the synthesis of a series of protected dipeptides containing hisfidine with unprotected imidazole group using DEPBT is reported. During the synthetic procedure, the imidazole group of histidine did not need to be protected. When the carboxyl components were N-protected aromatic amino acids or basic amino acids, the yields were relatively high (63%--81%). However,when the carboxyl components were N-protected acidic amino acids, the yields were relatively low (47%--48%). The results expanded the application of DEPBT on the synthesis of bioactive peptides containing histidine.     

Synthesis and application of dehydroabietylisothiocyante as a new chiral derivatizing agent for the enantiomeric separation of chiral compounds by capillary electrophoretic

A new chiral derivatizing reagent, dehydroabietylisothiocyante (DHAIC), was synthesized and used for the enantiomeric separation of chiral compounds in capillary electrophoresis (CE). The synthetic route to obtain DHAIC is described. The separation conditions for the chiral separation of several chiral compounds, such as protein amino acids and chiral drug DOPA were optimized. Best results for the chiral separation of DHAIC derivatized amino acids and DOPA were obtained in a running buffer consisted of 50 mM borate (pH 9.5), 5 mM sodium dodecyl sulphate (SDS) and 20% acetonitrile for amino acids and 60 mM Na₂HPO₄ (pH 8.0), 17 mM SDS and 25% acetonitrile for DOPA. Under the conditions studied, chiral separation of five amino acids including Ser, Val, Ala, Thr, Cys and a chiral drug DOPA as their diastereomeric DHAIC derivatives has been achieved by micellar electrokinetic chromatography (MEKC).     

含丝氨酸和组氨酸残基手性肽核酸单体的合成

设计合成了含组氨酸残基碱基为胸腺嘧啶的手性肽核酸单体, 咪唑氨基的最终保护基为2,4-二硝基苯基(Dnp). 对文献合成方法进行了适当改进, 制备了两种含丝氨酸和组氨酸残基碱基为腺嘌呤的手性肽核酸单体, 以上化合物均可作为制备手性肽核酸的基本构建单元.