甲氧基聚乙二醇-1,2-二硬脂酰甘油磷酰乙醇胺的合成

以1,2-二硬脂酸甘油酯为原料,依次与三氯氧磷和乙醇胺反应,得到1,2-二硬脂酰甘油磷酰乙醇胺(DSPE),其在N,N’-羰基二咪唑作用下与甲氧基聚乙二醇(mPEG2000)反应,生成甲氧基聚乙二醇2000-1,2-二硬脂酰甘油磷酰乙醇胺(mPEG2000-DSPE)。产物结构经过红外光谱、质谱及核磁氢谱等表征确证。     

聚乙二醇二丁二酸酯的合成

聚乙二醇在药物合成上有很广泛的用途,但其端羟基的活性相对较低,直接应用受到限制.若将羟基活化为羧基则可以扩大其应用范围;尤其是在合成二聚物时,将疏水链换成亲水的聚乙二醇二丁二酸酯链可以增加桥链的亲水性.为此,以聚乙二醇、丁二酸酐为反应物,以吡啶为溶剂,分别合成了一缩二乙二醇二丁二酸酯、二缩三乙二醇二丁二酸酯、三缩四乙二...     

聚乙二醇-异黄酮复合物的合成

用聚乙二醇(PEG)修饰异黄酮类化合物(1)的侧链,并采用不同氨基酸做连接臂,合成了聚乙二醇-异黄酮复合物--聚乙二醇-异黄酮酯前药(6),其结构经1H NMR和IR表征.在磷酸缓冲溶液中,1能在10 h内释放完全;6的载药量有待进一步提高.     

聚乙二醇衍生物的合成研究进展

功能化聚醚尤其是功能化聚乙二醇衍生物,如聚乙二醇对甲苯磺酸酯、胺基聚乙二醇、羧基聚乙二醇、聚乙二醇－聚酯及聚乙二醇－聚氨基酸共聚物等在有机合成、多肽合成,高分子合成、药物的缓释控释、靶向施药等多方面具有广泛的应用前景,目前它已成为国内外研究的热点,本文综述了近年来聚乙二醇衍生物的合成研究进展。     

牛血清蛋白对二硬脂酰基磷脂酰乙醇胺单层膜结构的影响

利用Langmuir-Blodgett(LB)技术结合原子力显微镜(AFM),研究了牛血清蛋白(BSA)在气/液界面上对二硬脂酰基磷脂酰乙醇胺(DSPE)单层膜结构的影响.通过改变亚相的pH值和BSA浓度,获得了不同条件下DSPE单层膜的等温线、吸附曲线和压缩循环曲线等.实验结果表明,亚相中BSA的存在对DSPE单层膜的压缩性、稳定性以及相变行为产生了较大的影响.吸附动力学结果表明,DSPE单层膜对BSA分子的吸附量存在一定的阈值,且该阈值的大小与亚相pH值相关.通过分析实验数据可知,当亚相pH=3时,BSA的疏水残基几乎全部暴露在外面,2种分子之间的相互作用最强;而pH=7时,BSA仅有少量的疏水残基暴露在外面,2种分子之间的相互作用最弱.原子力显微镜观测到的单层膜形态变化特点与曲线分析结果一致.该研究为了解牛血清蛋白与磷脂分子之间的相互作用机理提供了重要的实验基础和理论依据.     

磷脂酰乙醇胺型聚磷酸酯脂质体膜材的合成

以Ｐ，Ｐ－二氯磷酸β－－氯乙酯与季戊四醇的双脂肪酸酯为单体，通过缩聚反应合成磷酸酯，再经氨基化制备了四种磷酰乙醇胺型聚磷酸酯脂质膜材，用逆相蒸发法制备了脂质体，偏光显微镜及电镜表明，脂质体为大单层，以５－氟尿嘧啶为模型药物进行包封，测定了包封率和体外释放性能。     

1,2-双十六烷基-3-甘油-磷酸乙醇胺的合成研究

1,2-双十六烷基-3-甘油-磷酸乙醇胺(DHPE)属于甘油磷脂的一种,在生物学方面具有广泛的应用.报道了化合物DHPE的合成,合成路线以(S)-(+)-甘油醇缩丙酮、十六醇、乙醇胺为起始原料,得到了关键中间体1,2-双十六烷基甘油醇和Boc保护乙醇胺,然后通过Still-Gennari试剂将二者进行偶联,随后利用Horner-Wadsworth-Emmons反应高效的脱去磷脂上的乙酸甲酯基团,最终经过8步反应,以32%的总收率得到目标化合物DHPE.     

选择性聚乙二醇化赖氨酸的合成

以单甲氧基聚乙二醇(mPEG)和Fmoc-Lys(Boc)-OH(1)为主要原料,经过羧基苄酯化、侧链Boc脱除、ε-氨基丁二酸酐修饰得到功能化的赖氨酸化合物N-α-芴甲氧羰基-N-ε-(γ-氧代丁酸)-L-赖氨酸苄酯(4);1和4分别与mPEG在偶联剂D IC/HOB t的作用下联接,最终分别实现了赖氨酸主链和侧链的mPEG定点修饰,合成了新型的N-α-芴甲氧羰基-N-ε-(γ-氧代丁酸聚乙二醇酯)-L-赖氨酸苄酯(5,总收率52.6%)和N-ε-叔丁氧羰基-N-α-芴甲氧羰基-L-赖氨酸聚乙二醇酯(6,收率93.7%),其结构经1H NMR,IR和MS表征。     

脂质体药用辅料DMPG的合成研究

以三氯氧磷、1,2-二肉豆蔻酰甘油及甘油缩丙酮为原料,通过磷酰化、水解等反应合成1,2-二肉豆蔻酰磷脂酰甘油(DMPG),反应收率为75.8%,其结构经过IR,MS,~1H NMR及~(13)C NMR等确证。该合成方法具有操作简单、条件温和、收率高等特点。     

1,2-二乙酰氧甲基碳硼烷的合成

以6,9-二乙腈十硼烷和1,4-二乙酰氧基-2-丁炔为原料,合成了高纯度的1,2-二乙酰氧甲基碳硼烷,产率81.2%,纯度96.2%,其结构经UV-Vis,<'1>H NMR,<'11>B N-MR,IR和元素分析表征.     

Identification and quantification of polyethylene glycol types in polyethylene glycol methyl ether and polyethylene glycol vinyl ether

Quantitative determination of polyethylene glycol (PEG) impurities in two monofunctional polyglycol types, PEG methyl ether (M-PEG) and PEG vinyl ether (V-PEG), has been carried out by reversed-phase liquid chromatography with evaporative light scattering detection (ELSD). In addition to optimizing the resolution between PEG and monofunctional PEG peaks, the major focus has been to determine the molecular weights of PEG impurities in M-PEG and V-PEG of diverse molecular weights. The latter is achieved by examining liquid chromatography–mass spectrometry (LC–MS) mass spectra of both monofunctional PEG and PEG in several cases, and matching peak retention times with those of available PEG standards for all M-PEG and V-PEG sample types. This information is helpful in selecting the appropriate PEG standard to determine PEG content in each sample type. ELSD response factors for various PEG standards have also been compared. It has been found that PEG standards with molecular weights from 1000 Da to 8000 Da show responses that are within 10% of each other. However, a low molecular weight PEG such as PEG 400, provides approximately 30% less response compared to its higher molecular weight counterparts.     

Synthesis of functionalised polyethylene glycol derivatives of naproxen for biomedical applications

The preparation of a series of mono-naproxen functionalised polyethylene glycol derivatives have been achieved. These compounds feature several different terminal functional groups, the identities of which have been chosen to facilitate conjugation of these hybrid molecules to nanomaterials.     

(苯胺齐聚物-b-聚乙二醇)_3星型刚柔嵌段共聚物的合成

采用3种合成策略来制备(苯胺齐聚物-b-聚乙二醇)3三臂星型刚柔嵌段共聚物,获得了预期的目标产物.对每一种合成策略中各阶段的产物进行了结构表征,分析讨论了氧化偶联策略A和"先臂后核"缩合策略B的优点以及存在的问题,最终发展了简单、高效的"先核后臂"缩合策略C,即从均苯三甲酰氯和氨基/羧基封端苯胺四聚体出发,通过酰基化反应得到单分散的苯胺四聚体星型中间体M03,然后以1-乙基-(3-二甲基氨基丙基)碳酰二亚胺盐酸盐(EDCI)和4-二甲氨基吡啶(DMAP)为催化剂,使星型中间体M03与聚乙二醇单甲醚(m-PEG 550)经过脱水缩合反应得到(苯胺四聚体-b-聚乙二醇)3星型刚柔嵌段共聚物,并用红外光谱、质谱、核磁氢谱等进行了表征,表明所获得的产物与预期结构一致.     

Synthesis of 3-amino 1H-pyrazoles catalyzed by p-toluene sulphonic acid using polyethylene glycol-400 as an efficient and recyclable reaction medium

Abstract

An efficient synthesis of 3-amino 1H-pyrazoles is described. The reaction of β-keto nitriles with hydrazines in the presence of a catalytic amount of p-toluene sulphonic acid using polyethylene glycol-400 as an efficient and recyclable reaction medium afforded the corresponding 3-amino 1H pyrazoles excellent yields.     

Linear oligosulfoxides: Synthesis and solubility studies

Synthesis of three linear oligosulfoxides containing up to six sulfoxide groups was achieved by multiple S_N2 reactions between an alkanethiol and alkyl tosylate to give a linear oligosulfide followed by oxidation of the oligosulfide with sodium periodate to give an oligosulfoxide. The challenge of complete avoidance of partial oxidation and over oxidation was easily overcome using the sodium periodate oxidation conditions. Although sulfoxide is a highly polar functional group, the oligosulfoxides were found to have limited solubility in many solvents including DMSO and water, which disobeys the “like dissolves like” rule. The surprising solubility pattern of oligosulfoxides was discussed in the context of the drastically different solubility patterns of polyethylene glycol (PEG), poly(butylene oxide), and poly(methylene oxide). According to a dissolution model, solubility properties of linear oligomers including the oligosulfoxides and PEGs may be heavily affected by their conformations and the suitability of their conformations in water for maximizing attractive interactions between them and water. Based on these hypotheses, the limited solubility of the present oligosulfoxides may not imply the low solubility of similar molecules.     

聚乙二醇-硫酸铵-二甲酚橙体系萃取分离钯

研究了萃取剂二甲酚橙与Pd(Ⅱ)离子的螯合物在聚合物-硫酸铵-水体系中两相间的分配行为。在pH1．0～6．0条件下，Pd(Ⅱ)几乎被二甲酚橙完全萃取到PEG相中，而Fe(Ⅱ)、Co(Ⅱ)、Zn(Ⅱ)萃取率随pH变化显著，Mn(Ⅱ)、Cd(Ⅱ)基本不被萃取。在HClO4介质pH1．0～2．0条件下，实现了Pd(Ⅱ)与Fe(Ⅱ)、Co(Ⅱ)、Zn(Ⅱ)、Mn(Ⅱ)、Cd(Ⅱ)的定量萃取分离。     

Denitrogenation of acrylonitrile-butadiene-styrene copolymers using polyethylene glycol/hydroxides

Alkaline hydrolysis of acrylonitrile-butadiene-styrene (ABS) copolymers has been systematically investigated to demonstrate the use of reaction systems based on polyethylene glycol (PEG)/hydroxides for N-elimination from ABS. The structure of denitrogenated ABS has been characterized using elemental analysis, FTIR, ¹H-NMR, and solid state ¹³C CP-MAS NMR, indicating sequential hydrolysis as a plausible mechanism of elimination of N from ABS. The effects of reaction conditions such as solvent selection, reaction temperature, alkaline species and concentration, as well as PEG molecular weight were evaluated. At optimal conditions (THF, PEG600, 4.3 wt % of NaOH), as much as 93.1% of the original nitrogen content of ABS was removed in 2 h at 160 °C, while it is only 35.6% without PEG. This clearly demonstrates the high-efficiency of a PEG/hydroxides catalytic system for denitrogenation of ABS, stressing the potential of this method for denitrogenation of other N-containing polymers.     

Separation of exenatide analogue mono-PEGylated with 40 kDA polyethylene glycol by cation exchange chromatography

Random PEGylation usually resulted in product mixtures composed of mono-PEGylated isomers and multi-PEGylated attachments. Generally in PEGylation research, separation of the mono-PEGylated isomers was the prerequisite for finding the optimal PEGylation site. However, when peptides or proteins were PEGylated with polyethylene glycol as large as 40 kDA, the physicochemical properties like hydrophobicity and molecular size of the isomers would become too similar to make the routine separation methods, like RP-HPLC, size-exclusion chromatography, SDS-PAGE and capillary isoelectric focusing invalid. This article presented a useful method of successfully separating exenatide analogue (an incretin for diabetic therapy) isomers mono-PEGylated with 40 kDA polyethylene glycol by cation exchange chromatography, which would be a powerful tool for the PEGylation research.