(2R,3S,4S)-2-(N,N-二乙氨基)甲酰氧基-3-苯基-4-苯甲酰基-N-甲基-γ-内酰胺的合成及工艺研究

目的：通过对黄皮酰胺全合成中间体（2R,3S,4S）-2-羟基-3-苯基-4-苯甲酰基-N-甲基-γ-内酰胺（化合物A）2位羟基的酯化,提高脂水分配系数（kP）,考察对谷丙转氨酶活性的影响。方法：以化合物A为原料,通过酰化反应合成（2R,3S,4S）-2-（N,N-二乙氨基）甲酰氧基-3-苯基-4-苯甲酰基-N-甲基-γ-内酰胺（化合物B）,重点考察了摩尔比、反应温度、反应时间等条件对反应的影响。化合物B结构已经元素分析、红外光谱、质谱及核磁共振氢谱确证。结果：化合物A和酰化剂以摩尔比2：3,在160℃下反应1h,目标化合物B。收率78．42％。结论：本合成路线及具体反应方法,具有试剂廉价易得、反应条件温和、后处理简便等优点,是一种较为实用的合成方法。     

(2R,3S,4S)-2-(N,N-二乙氨基)甲酰氧基-3-苯基-4-苯甲酰基-N-甲基-Y-内酰胺的合成及工艺研究

目的:通过对黄皮酰胺全合成中间体(2R,3s,4S)-2-羟基-3-苯基-4-苯甲酰基-N-甲基-Y-内酰胺(化合物A)2位羟基的酯化,提高脂水分配系数(1gP),考察对谷丙转氨酶活性的影响。方法:以化合物A为原料,通过酰化反应合成(2R,3S,4S)-2-(N,N-二乙氨基)甲酰氧基-3-苯基-4-苯甲酰基-N-甲基-Y-内酰胺(化合物B),重点考察了摩尔比、反应温度、反应时间等条件对反应的影响。化合物B结构已经元素分析、红外光谱、质谱及核磁共振氢谱确证。结果:化合物A和酰化剂以摩尔比2:3,在160℃下反应1h,目标化合物B,收率78．42%。结论:本合成路线及具体反应方法,具有试剂廉价易得、反应条件温和、后处理简便等优点,是一种较为实用的合成方法。     

2-芳基-1,3-二氧环戊烷的合成与表征

以3-硝基-4-甲基苯甲酸为主要原料,依次通过乙硼烷还原、氯代反应将其中羧基转化为氯甲基,又经过缩争、氧化、醛基保护将甲基转化为缩醛等步骤合成了2-[2-硝基-(4-氯甲基)]苯基-1,3-二氧环戊烷.目标产物及某些重要中间体的结构已通过红外光谱、质谱、核磁共振氢谱的方法进行了表征.     

β-内酰胺的合成方法

本方法是以(R)-3-羟基丁酸甲酯为初始原料,合成β-内酰胺(简写4-AA)的一条路线,它的优点是:其初始原料(R)-3-羟基丁酸乙酯是通过生物发酵生产的具有天然手性的P3hb通过高温高压裂解得来的。去除了以往纯化学合成手性拆分的麻烦,大大缩短了合成路线,而且此路线成本较低,有利于工业化。     

侧链含有鬼臼毒素高分子抗癌药物的合成

分别用可溶性淀粉,羧甲基纤维素钠和甲壳胺为载体与鬼臼毒素合成了三种侧链含有鬼臼毒素高分子抗癌药物。在pH7.4的缓冲溶液中对鬼臼毒基羰甲基淀粉,鬼臼毒基羰甲基纤维素和鬼臼毒基羰甲基甲壳胺的体外水解释放进行了考查。     

亮菌乙素的结构确证及其合成

利用柱层析从亮菌子实体的甲醇提取物中分离得到了亮菌乙素,经波谱分析确定亮菌乙素的最终结构为2-羟基-2-苯基-丙二酰胺.以苯马龙酸为原料经三步反应合成了亮菌乙素.     

2-甲基-4-硝基-吡啶-N-氧化物的合成方法研究

对2-甲基-4-硝基-吡啶-N-氧化物的合成方法进行了工艺改进,以2-甲基吡啶为原料,经氧化、硝化合成目标产物。总产率达到70.36%。     

寡核苷酸合成的一种优化方法

为提高寡核苷酸的合成效率,结合本实验室研制出的探针并行合成装置,提出了一种寡核苷酸合成的优化方法,可有效减少合成的循环次数,同时使合成成本降低、合成时间缩短,合成效率大大提高。     

药物合成中的氨基化合物环合反应

随着我国社会经济的发展,也相应的促进了我国医药行业的发展,通过不断的进行医药研究,进而研究出更多的医药,促进相关疾病治疗的康复。因此,本文针对于药物合成中的氨基化合物的环合反应进行了相关方面的探讨,希望通过本文的分析,能够为相关方面的研究提供理论性的参考。     

合成寡核苷酸的简易纯化方法

由手工或机器合成寡核苷酸到使用它们的过程中,纯化步骤经常成为速度限制因素,因为目前采用的常规纯化方法比较繁复,特别当样品数和每份样品量多时,往往难以满足工作的需求。有鉴于此,1986年Lloyd等报道了一个简易的纯化方法,似可克服上述不足。笔者从1986年以来曾多次参照Lloyd等法(仅在某些细节上略作改变)纯化由合成机合成的脱氧寡核苷酸片段(其长度为30-mer—50-mer),效果不错,在此作一介绍,以供参考。     

First enzymatic synthesis of water-soluble conducting poly(3,4-ethylenedioxythiophene)

The enzymatically catalyzed polymerization of 3,4-ethylenedioxythiophene in the presence of polystyrenesulfonate is introduced. This is the first time that an enzymatically catalyzed poly(3,4-ethylenedioxythiophene) (PEDOT) is reported. Horseradish peroxidase enzyme was used as a catalyst for the polymerization process leading to a water-soluble PEDOT that was characterized by UV-vis spectra, Fourier transform infrared, and electrical conductivity measurements. Water-soluble PEDOT showed excellent film formation ability as confirmed by atomic force microscopy images.     

Synthesis,copolymerization and peptide-modification of carboxylic acid-functionalized 3,4-ethylenedioxythiophene (EDOTacid) for neural electrode interfaces

Background

Conjugated polymers have been developed as effective materials for interfacing prosthetic device electrodes with neural tissue. Recent focus has been on the development of conjugated polymers that contain biological components in order to improve the tissue response upon implantation of these electrodes.

Methods

Carboxylic acid-functionalized 3,4-ethylenedioxythiophene (EDOTacid) monomer was synthesized in order to covalently bind peptides to the surface of conjugated polymer films. EDOTacid was copolymerized with EDOT monomer to form stable, electrically conductive copolymer films referred to as PEDOT-PEDOTacid. The peptide GGGGRGDS was bound to PEDOT-PEDOTacid to create peptide functionalized PEDOT films.

Results

The PEDOT-PEDOTacid-peptide films increased the adhesion of primary rat motor neurons between 3 and 9 times higher than controls, thus demonstrating that the peptide maintained its biological activity.

Conclusions

The EDOT-acid monomer can be used to create functionalized PEDOT-PEDOTacid copolymer films that can have controlled bioactivity.

General Significance

PEDOT-PEDOTacid-peptide films have the potential to control the behavior of neurons and vastly improve the performance of implanted electrodes. This article is part of a Special Issue entitled Organic Bioelectronics—Novel Applications in Biomedicine.     

Biological response of protists Haematococcus lacustris and Euglena gracilis to conductive polymer poly (3,4-ethylenedioxythiophene) polystyrene sulfonate

Improving the growth and pigment accumulation of microalgae by electrochemical approaches was considered a novel and promising method. In this research, we investigated the effect of conductive polymer poly (3,4-ethylenedioxythiophene) polystyrene sulfonate (PEDOT:PSS) dispersible in water on growth and pigment accumulation of Haematococcus lacustris and Euglena gracilis. The results revealed that effect of PEDOT:PSS was strongly cell-dependent and each cell type has its own peculiar response. For H. lacustris, the cell density in the 50 mg·l⁻¹ treatment group increased by 50·27%, and the astaxanthin yield in the 10 mg·l⁻¹ treatment group increased by 37·08%. However, under the high concentrations of PEDOT:PSS treatment, cell growth was significantly inhibited, and meanwhile, the smaller and more active zoospores were observed, which reflected the changes in cell life cycle and growth mode. Cell growth of E. gracilis in all the PEDOT:PSS treatment groups were notably inhibited. Chlorophyll a content in E. gracilis decreased while chlorophyll b content increased in response to the PEDOT:PSS treatment. The results laid a foundation for further development of electrochemical methods to promote microalgae growth and explore the interactions between conductive polymers and microalgae cells.     

Biomimetic synthesis of water-soluble conducting copolymers/homopolymers of pyrrole and 3,4-ethylenedioxythiophene

A novel biomimetic route for the synthesis of electrically conducting homopolymers/copolymers of pyrrole and 3,4-ethylenedioxythiophene (EDOT) in the presence of a polyelectrolyte, such as polystyrene sulfonate (SPS), is presented. A poly(ethylene glycol)-modified hematin (PEG-hematin) was used to catalyze the homopolymerization of pyrrole and EDOT as well as copolymerization of EDOT and pyrrole in the presence of SPS to yield homopolymers of polypyrrole/SPS and PEDOT/SPS as well as a polypyrrole-co-poly(3,4-ethylenedioxythiophene)/SPS complex. Spectroscopic characterization [UV-visible, Fourier transform infrared (FTIR), and X-ray photoelectron spectroscopy (XPS)], thermal analysis, (TGA), and electrical conductivity studies for these complexes indicated the presence of a stable and electrically conductive form of these polymers. Furthermore, the presence of SPS that serves as a charge-compensating dopant in this complex provides a unique combination of properties such as processability and water solubility.     

Synthetic approaches to 6-substituted 9-(3-azido-3,4-dideoxy-β-d,l-erythro-pentopyranosyl)purines

Methyl 3-azido-2-O-benzoyl-3,4-dideoxy-β-dl-erythro-pentopyranoside (6) was synthesized through two routes in five steps from methyl 2,3-anhydro-4-deoxy-β-dl-erythro-pentopyranoside (1). The first route proceeded via selective azide displacement of the 3-tosyloxy group of methyl 4-deoxy-2,3-di-O-tosyl-α-dl-threo-pentopyranoside, followed by detosylation and benzoylation. The second route consisted, with a better overall yield, in the azide displacement of the mesyloxy group of methyl O-benzoyl-4-deoxy-3-O-methylsulfonyl-α-dl-threo-pentopyranoside (10), obtained by benzylate opening of 1, followed by benzoylation, debenzylation, and mesylation. Compound 6 was transformed into its glycosyl chloride, further treated by 6-chloropurine to give the nucleoside 9-(3-azido-2-O-benzoyl-3,4-dideoxy-β-dl-erythro-pentopyranosyl)-6-chloropurine (13). When treated with propanolic ammonia, 13 yielded 9-(3-azido-3,4-dideoxy-β-dl-erythro-pentopyranosyl)adenine.     

Synthesis of (3,4) beta-methylenecepham and (3,4) beta-methylene-carbacepham via intramolecular carbene addition to double bond

A series of new (3,4) beta-methylenecepham and carbacepham analogues were synthesised as potential antibacterial agents. The key step of the synthesis included presumed generation of the carbene species from the oxalimide substrate effected by triethylphosphite and its intramolecular addition to the double bond. The stereochemistry of the tricyclic system has been elucidated by NMR and X-ray crystallography. In preliminary screening, two of the synthesised compounds exhibited modest antibacterial activity at 1.5-2.0 mg/mL against a number of bacterial strains.     

Atypical membrane-embedded phosphatidylinositol 3,4-bisphosphate (PI(3,4)P2)-binding site on p47(phox) Phox homology (PX) domain revealed by NMR

The Phox homology (PX) domain is a functional module that targets membranes through specific interactions with phosphoinositides. The p47(phox) PX domain preferably binds phosphatidylinositol 3,4-bisphosphate (PI(3,4)P(2)) and plays a pivotal role in the assembly of phagocyte NADPH oxidase. We describe the PI(3,4)P(2) binding mode of the p47(phox) PX domain as identified by a transferred cross-saturation experiment. The identified PI(3,4)P(2)-binding site, which includes the residues of helices α1 and α1' and the following loop up to the distorted left-handed PP(II) helix, is located at a unique position, as compared with the phosphoinositide-binding sites of all other PX domains characterized thus far. Mutational analyses corroborated the results of the transferred cross-saturation experiments. Moreover, experiments with intact cells demonstrated the importance of this unique binding site for the function of the NADPH oxidase. The low affinity and selectivity of the atypical phosphoinositide-binding site on the p47(phox) PX domain suggest that different types of phosphoinositides sequentially bind to the p47(phox) PX domain, allowing the regulation of the multiple events that characterize the assembly and activation of phagocyte NADPH oxidase.     

A [Ni(cyclam)]2+-functionalised poly(3,4-ethylenedioxythiophene): Synthesis,electropolymerisation and characterisation of the polymer by cyclic voltammetry and in situ reflectance FTIR spectroscopy

A 1,4,8,11-tetraazacyclotetradecane (cyclam) derivative of 3,4-ethylenedioxythiophene (EDOT) has been synthesised. Its square planar Ni(II) tetrafluoroborate complex has been electrochemically polymerised, with EDOT itself, to give a highly stable conducting polymer with covalently attached [Ni(cyclam)]²⁺ moieties. The cyclic voltammogram shows redox behaviour typical of a functionalised PEDOT, with the reversible Ni(II)–Ni(III) process of the [Ni(cyclam)]²⁺ complex superimposed. Reflectance in situ FTIR spectroscopy (RIFTIRS) shows that the presence of the metal complex has a profound influence upon the behaviour of the electronic band of the oxidised form of the polymer, and of the vibrational signature due to the charge carriers.     

水飞蓟素提取工艺的改进和探讨

对水飞蓟种皮中的水飞蓟素提取方法进行初步研究。实验采用乙酸乙酯超声波辅助浸提,水飞蓟素提取率可达到7．0％以上,且缩短提取时间（〈10h）,在甲醉体系下3次重结晶,水飞蓟宾纯度可达到97．0％。原料收率为7．07mg／g。研究认为,水飞蓟种子皮壳分离对提高产品质量和资源利用价值有显著意义。     

Redox self-sufficient biocatalyst system for conversion of 3,4-Dihydroxyphenyl-l-alanine into (R)- or (S)-3,4-Dihydroxyphenyllactic acid

Journal of Industrial Microbiology & Biotechnology - We developed an efficient multi-enzyme cascade reaction to produce (R)- or (S)-3,4-Dihydroxyphenyllactic acid [(R)- or (S)-Danshensu, (R)-...