主链含氨基酸、5-氟尿嘧啶和膦甲酸乙酯(膦乙酸乙酯)的聚磷酰胺和聚磷酸酯的合成及抗肿瘤活性研究

由1,3-双(氨基酸丙酯盐酸盐)-5-氟尿嘧啶与膦甲(乙)酸乙酯在DMF中反应制得二十种主链含氨基酸、膦甲(乙)酸乙酯和5-氟尿嘧啶三组分的聚合物。通过核磁、红外和紫外光谱以及元素分析测定了聚合物的结构。并试验了聚合物的体外抗肿瘤活性。     

氨基酸5—氟尿嘧啶酯类衍生物的合成及其抗肿瘤活性研究

用氨基酸作抗癌药物载体以提高对癌细胞选择性的研究引起了人们的浓厚兴趣。在前文中,我们报道了5-氟尿嘧啶乙酰和丙酰氨基酸及其氨基酸的3-(N′-5-氟尿嘧啶基)-丙醇酯的合成及其抗肿瘤试验研究。本文将报道一系列氨基酸(5-氟尿嘧啶-1,3-双丙基)酯盐酸盐的合成及其体外抗肿瘤活性的研究。 合成路线如下:     

聚5-氟尿嘧啶-1-乙酰天冬氨酰二胺的合成及其抗肿瘤活性

本文报道5-氟尿嘧啶-1-乙酰天冬氨酸,5-氟尿嘧啶-1-乙酰天冬氨酸双对硝基苯酯的合成。并用5-氟尿嘧啶-1-乙酰天冬氨酸双对硝基苯酯与一系列α,ω-二胺或赖氨酸乙酯缩聚,合成了五个聚5-氟尿嘧啶-1-乙酰天冬氨酰二胺和一个聚5-氟尿嘧啶-1-乙酰天冬氨酰赖氨酸乙酯。用~1HNMR,IR,UV和元素分析表征和签定了所得的单体和聚合物。抗动物肿瘤试验结果表明:聚5-氟尿嘧啶-1-乙酰天冬氨酰戊二胺,聚5-氟尿嘧啶-1-乙酰天冬氨酰赖氨酸乙酯,对小鼠艾氏腹水癌的抑制率分别为31.85％,44.23％。     

高分子药物研究——Ⅻ.侧链含5-氟尿嘧啶聚酰胺的合成及其抗肿瘤活性研究

本文用N-(5-氟尿嘧啶乙酰)谷氨酸双对硝基苯酯与一系列α、ω-多次甲基二胺缩聚制备了6种侧链含5-氟尿嘧啶的聚酰胺。通过元素分析、核磁共振谱、红外光谱和紫外光谱对单体和聚合物的结构进行了鉴定。经初步抗动物肿瘤试验,聚α-(5-氟尿嘧啶乙酰胺基)戊二酰乙二胺对艾氏腹水癌的抑制率为43.0％。     

N~1羟烷基-5-氟尿嘧啶和α-5-氟尿嘧啶-N~1-二羧酸的研究

5-氟尿嘧啶(5-FU)是一种广谱性的抗肿瘤药物,其主要缺点是脂溶性小,口服吸收困难,毒副作用较大。为此,多年来,对5-FU进行了大量的化学修饰工作。已成功用于临床的5-FU衍生物主要有呋喃啶(FT-207),双呋喃啶(Thf_2-5-FU)、氟尿嘧啶脱氧核苷(FUDR)及卡莫氟(HCFU)等。在前文中,我们报道了1,3-二羟烷基-5-氟尿嘧啶和氨基酸短肽负载的5-氟尿嘧啶的合成及其抗肿瘤活性。     

含5-氟尿嘧啶生物可降解聚磷酰胺的合成及其抗肿瘤活性研究

通过L-赖氨酸(N¹-5-氟尿嘧啶)烷基酯双盐酸盐与二氯磷酸乙酯、二氯膦甲酸乙酯、二氯膦乙酸乙酯共聚,合成了三类12种侧链含5-氟尿嘧啶的聚磷酰胺。聚合物的结构经UV、IR、¹H NMR及元素分析鉴定。聚合物用微量细胞培养四氮唑实验方法(MTT法)进行了对人肝癌细胞系Bel-7402细胞的微量培养实验。     

氨基酸5-氟尿嘧啶酯类衍生物的合成及其抗肿瘤活性研究

以N-保护的氨基酸钾盐与1-(ω-溴丙基)-5-氟尿嘧啶和1-(ω-溴丁基)-5-氟尿嘧啶反应,制备了18种氨基酸的ω-(N¹-5-氟尿嘧啶基)-丙醇酯和丁醇酯的盐酸盐,并确定了它们的结构。动物试验的初步结果表明,酪氨酸、苯丙氨酸的3-(N¹-5-氟尿嘧啶基)-丙醇酯盐酸盐对小鼠艾氏腹水癌的抑制率分别为88.1%和86.7%。     

5-氟尿嘧啶短肽的合成及其抗肿瘤活性研究

5-氟尿嘧啶乙酸对-硝基苯酯和5-氟尿嘧啶丙酸对-硝基苯酯分别与三种二肽反应,制备了五个5-氟尿嘧啶二肽(4 a-e)。以5-氟尿嘧啶的氨基酸对-硝基苯酯(2 a-c)分别和三种二肽反应,制得四个5-氟尿嘧啶三肽(5 a-d)。产物经元素分析、NMR、IR和UV鉴定。初步动物试验表明:5-氟尿嘧啶丙酰甘-苯丙二肽,5-氟尿嘧啶乙酰甘-甘-苯丙三肽和5-氟尿嘧啶乙酰缬-亮-甘三肽对小白鼠移植性艾氏腹水癌有一定的抑制作用。     

5-氟尿嘧啶N1-甲酰基氨基酸、短肽的合成及抗肿瘤活性

5-氟尿嘧啶N¹-甲酰氯分别与Gly、Val、Leu、Ile、Phe、Asp和Glu的苄酯反应,制备了7种5-氟尿嘧啶-N¹-甲酰基氨基酸苄酯。氢解后得到了相应的5-氟尿嘧啶N¹-甲酰氨基酸。将其进一步与氨基酸甲酯或二肽甲酯缩合,制备了5-氟尿嘧啶N¹-甲酰基二肽甲酯和三肽甲酯。5-氟尿嘧啶-N¹-甲酰基二肽甲酯也可采用5-氟尿嘧啶-N¹-甲酰氯与二肽甲酯直接反应制备。     

5-氟尿嘧啶短钛的合成及其抗肿瘤活性研究

5-氟尿嘧啶乙酸对-硝基苯酯和5-氟尿嘧啶丙酸对-硝基苯酯分别与三种二肽反应,制备了五个5-氟尿嘧啶二肽(4aα-e).以5-氟尿嘧啶的氨基酸对-硝基苯酯(2a-c)分别和三种二肽反应,制得四个5-氟尿嘧啶三肽(5A-d).产物经元素分析,NMR,IR和UV鉴定.初步动物试验表明:5-氟尿嘧啶丙酰甘-苯丙二肽,5-氟尿嘧啶乙酰甘-甘-苯丙三肽和5-氟尿嘧啶乙酰缬-亮-甘三肽对小白鼠移植性艾氏腹水癌有一定的抑制作用.     

Chiral soluble polymers and microspheres for enantioselective crystallization

A series of chiral polymers based on poly(N‐acryl) amino acids was synthesized using a convergent synthetic approach. These chiral polymers have been used as chiral additives to induce enantioselective crystallization of racemic or conglomerate amino acids in solutions. These polymeric additives showed strong capabilities to enhance highly enantioselective resolution during the crystallization of amino acids. In addition, these polymers caused unusual modifications of amino acid crystal morphologies. Furthermore, spherical microparticles of those same chiral polymers were also shown active in similar chiral discriminations during amino acid crystallizations occurring on microparticle surfaces. Our study demonstrates the high potential of chiral polymers and microparticles to resolve amino acids throughout crystallization processes. High enantiomeric excesses in one targeted enantiomer of amino acids can also be maximized via time‐dependent kinetic control of crystallizations. © 2006 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 44: 3009–3017, 2006     

Preparation of new membranes based on sulfonated aromatic copolyimides

New sulfonated aromatic copolyimides with controlled degree of sulfonation were prepared via polycondensation reactions of a sulfonated diamine and two unsulfonated diamines with 1,4,5,8‐naphthalene tetracarboxylic dianhydride (NDA). The sulfonated diamine 3,3′‐disulfonic acid‐ bis[4‐(5‐amino‐1‐naphthoxy)phenyl]sulfone (DANPS) was synthesized through nucleophilic substitution reaction of 5‐amino‐1‐naphthol with disodium‐3,3′‐disulfonate‐4,4′‐dichlorodiphenysulfone (SDCDPS) and subsequent acidification. Two unsulfonated diamines 4,4′‐(5‐amino‐1‐naphthoxy)diphenylsulfone (ANDS) and 4,4′‐(4‐aminophenoxy)diphenylsulfone (APDS) were prepared by nucleophilic reaction of 5‐amino‐1‐naphthol and 4‐aminophenol with 4,4′‐dichlorodiphenylsulfone in the presence of potassium carbonate, respectively. After characterization of the monomers and polymers with common methods, the physical properties of the polymers including thermal behavior and stability, viscosity, molecular weight, and ion exchange capacity (IEC) were studied. The polymers showed high thermal stability and ion exchange capacity which were the basic requirements for application as fuel cell membranes. Copyright © 2008 John Wiley & Sons, Ltd.     

SYNTHESIS OF CONDENSATION POLYMERS OF SALICYLIC ACID, FORMALDEHYDE AND ALKYL PRIMARY AMINES AND ITS APPLICATION AS A CATALYST FOR THE HYDROLYSIS OF p-NITROPHENYL ACETATE (PNPA) IN AQUEOUS SOLUTION

As a model of serine hydrolase, the condensation polymers of salicylic acid, formaldehyde and methyl amine, n-propyl amine, n-hexyl amine or n-lauryl amine were prepared by polycondensation catalyzed by sulfuric acid. It was confirmed by potentiometric titration and infrared spectrum that the polymers containing tertiary amino group possess the structure which resembles the internal salt of amino acid in weak basic and weak acidic solution:     

Synthesis and radical ring‐opening polymerization of vinylcyclopropanes derived from amino acids with hydrophobic moieties

Six 1,1‐disubstituted vinylcyclopropanes (VCP) were synthesized from glycine and amino acids bearing hydrophobic moieties, l ‐alanine, l ‐valine, l ‐leucine, l ‐isoleucine, and l ‐phenylalanine. These VCP derivatives efficiently underwent radical ring‐opening polymerization to afford the corresponding polymers bearing trans‐vinylene moiety in the main chains and the amino acid‐derived chiral moieties in the side chains. The polymers were film‐formable, and in the films of polymers bearing the glycine‐ and alanine‐derived side chains, presence of hydrogen bonding was confirmed by IR analysis. Thermogravimetric analysis of the polymers revealed that the temperatures of 5% weight loss were higher than 300 °C. Differential scanning calorimetry clarified that the polymers were amorphous ones showing glass transition temperatures in a range of 48–80 °C. © 2017 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2017 , 55, 3996–4002     

Synthesis and specific biodegradation of novel polyesteramides containing amino acid residues

Novel polyesteramides were synthesized from p‐nitrophenyl esters of sebacic or adipic acids and diamines containing α‐amino acid ester groups. The optimal polymerization condition was 60 °C in N,N‐dimethylformamide. The structures of these polymers were confirmed by IR and NMR. The number‐average molecular weights of these polyesteramides ranged from 2280 to 23,600 (except for the polymers containing glycine residues), depending on the nature of the amino acid used. The biodegradability of the polyesteramides was investigated by in vitro hydrolysis with proteases and a lipase as catalysts in borate buffer solutions. The results indicated that the polymers containing L ‐phenylalanine were hydrolyzed most effectively by α‐chymotrypsin, subtilisin Carlsberg, and subtilisin BPN′. The polyesteramides containing other amino acid residues also underwent hydrolysis to different extents, reflecting the substrate specificity of the proteases. Lipase had almost no effect on the hydrolytic degradation of these polyesteramides. The polymers containing glycine residues were hardly decomposed by any of the enzymes used. © 2001 John Wiley & Sons, Inc. J Polym Sci A: Polym Chem 39: 1318–1328, 2001     

Capillary electrochromatographic separation of amino acid enantiomers with molecularly imprinted polymers as chiral recognition agents

The use of molecularly imprinted polymers polymerized in a capillary for the separation of amino acid enantiomers by electrochromatography is described. The substrate-selective polymers were prepared by using l-phenylalanine anilide as print molecule and methacrylic acid as the functional monomer. The treatment of the inside surface of the capillary, the composition of the polymer and the electrochromatographic running conditions were investigated. This preliminary report demonstrated a novel and simple method for capillary electrochromatographic separations of amino acid enantiomers using molecularly imprinted polymers. Received: 9 April 1996 / Revised: 8 August 1996 / Accepted: 8 August 1996     

Pendant structure governed anion sensing property for sulfonamide‐functionalized poly(phenylacetylene)s bearing various α‐amino acids

The colorimetric detection of anionic species has been studied for α‐amino acid‐conjugated poly(phenylacetylene)s, which were prepared by the polymerization of the ethyl esters of N‐(4‐ethynylphenylsulfonyl)‐L ‐alanine, L ‐isoleucine, L ‐valine, L ‐phenylalanine, L ‐aspartic acid, and L ‐glutamic acid using Rh⁺(2,5‐norbornadiene)[(η⁶‐C₆H₅)B^?(C₆H₅)₃] as the catalyst in CHCl₃. The one‐handed helical conformations of all the sulfonamide‐functionalized polymers were characterized by Cotton effects in the circular dichroism spectra. The addition of anions with a relatively high basicity, such as tetra‐n‐butylammonium acetate and fluoride, induced drastic changes in both the optical and chiroptical properties. On the other hand, anions with a relatively low basicity, such as tetra‐n‐butylammonium nitrate, azide, and bromide, had essentially no effects on the helical conformation of all the sulfonamide‐functionalized polymers. The anion signaling property of the sulfonamide‐functionalized polymers possessing α‐amino acid moieties was significantly affected by the installed residual amino acid structures. © 2010 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 48: 1683–1689, 2010     

生物降解聚合物的研究和产业化进展及展望

结合作者等近十年来在生物降解聚合物领域的研究和产业化工作,本文概述了聚乳酸、聚氨基酸、聚对二氧六环酮及其它生物降解聚合物的合成进展,综述了可生物降解温度敏感水凝胶、形状记忆高分子材料的研究概况,阐述了可生物降解聚合物在生物活性大分子控释体系、超细纤维组织工程支架上的应用研究,介绍了可生物降解聚合物在食品包装、纺织和汽车电子等方面的应用,总结了可生物降解聚合物、医疗器械、药物制剂和组织工程等领域产业化近况.最后展望了生物降解聚合物的研究、应用和产业化前景.     

Novel Flame‐Retardant and Thermally Stable Poly(Amide‐imide)s Based on Bicyclo[2,2,2]oct‐7‐Ene‐2,3,5,6‐Tetracarboxylic Diimide and Phosphine Oxide in the Main Chain: Synthesis and Characterization

Six novel poly(amide‐imide)s PAIs 5a‐f were synthesized through the direct polycondensation reaction of six chiral N,N′‐(bicyclo[2,2,2]oct‐7‐ene‐tetracarboxylic)‐bis‐L‐amino acids 3a‐f with bis(3‐amino phenyl) phenyl phosphine oxide 4 in a medium consisting of N‐methyl‐2‐pyrrolidone (NMP), triphenyl phosphite (TPP), calcium chloride (CaCl₂) and pyridine. The polymerization reaction produced a series of flame‐retardant and thermally stable poly(amide‐imide)s 5a‐f with high yield and good inherent viscosity of 0.39–0.83 dLg^?1. The resultant polymers were fully characterized by means of FTIR, ¹H NMR spectroscopy, elemental analyses, inherent viscosity, specific rotation and solubility tests. Thermal properties and flame retardant behavior of the PAIs 5a‐f were investigated using thermal gravimetric analysis (TGA and DTG) and limited oxygen index (LOI). Data obtained by thermal analysis (TGA and DTG) revealed that these polymers show good thermal stability. Furthermore, high char yields in TGA and good LOI values indicated that resultant polymers exhibited good flame retardant properties. N,N′‐(bicyclo[2,2,2]oct‐7‐ene‐tetracarboxylic)‐bis‐L‐amino acids 3a‐f were prepared in quantitative yields by the condensation reaction of bicyclo[2,2,2]oct‐7‐ene‐2,3,5,6‐tetracarboxylic dianhydride 1 with L‐alanine 2a , L‐valine 2b , L‐leucine 2c , L‐isoleucine 2d , L‐phenyl alanine 2e and L‐2‐aminobutyric acid 2f in acetic acid solution. These polymers can be potentially utilized in flame retardant thermoplastic materials.     

Bioconjugates of smart polymers and proteins: synthesis and applications

Over the past 20 years we have been deeply involved with the synthesis and applications of stimuli-responsive polymer systems, especially polymer-biomolecule conjugates. The work of Toyoichi Tanaka has been a constant inspiration for our work and this article is dedicated to him. This article summarizes the research that we have carried out along with many collaborators on polymer-protein conjugates. We include conjugates prepared by random polymer conjugation to lysine amino groups, and also those prepared by site-specific conjugation of the polymer to specific amino acid sites that are genetically-engineered into the known amino acid sequence of the protein. We describe the preparation and properties of thermally-sensitive, random conjugates to enzymes and several affinity recognition proteins. We have also prepared site-specific conjugates to streptavidin. with temperature-sensitive polymers, pH-sensitive polymers, and light-sensitive polymers. The preparation of these conjugates and their many fascinating applications are reviewed in this article.