Novel Phosphonoacetic Acid Derivatives.Synthesis of N-(Ethoxycarbonylmethylphosphonyl)-α-Amino Esters and-α-Amino Phosphonic Acid Esters and Their Bioactivities

A series of novel phosphonoacetic acid derivatives, N-(ethoxycarbonylmethy-ethoxyphosphonyl)-α-amino acid esters and α-amino phosphonates, were synthesized via the reaction of the corresponding phosphonyl chloride with amino acid ester hydrochlorides or amino phosphonates in the presence of a base. The preliminary bioassay shows that some compounds show significant anti-viral activity against tobacco mosaic virus (TMV)

N-羟基邻苯二甲酰亚胺酯(NHP酯)的合成方法研究

报道了一种N-羟基邻苯二甲酰亚胺酯(NHP酯)的合成方法,我们采用商业化的氨基酸为原料,对氨基酸上的氨基进行修饰,然后与N-羟基邻苯二甲酰亚胺发生酯化反应,可以得到具有不同取代基的NHP酯,该方法操作简单,安全可靠,是一种可以用于有机合成的新策略。

手性磷酸催化非环状N,N′-缩酮的不对称合成

手性N,N′-缩酮是药物分子和生物活性化合物最重要的核心结构之一,也是有机合成中重要的催化剂或配体。因此,不对称合成N,N′-缩酮具有重要意义。通过手性磷酸、溶剂、催化剂负载量和投料比的筛选,确定了最佳的反应条件:在手性磷酸的催化下,以1,4-二氧六环作为溶剂,5-氨基异噁唑与β,γ-炔基-α-酮亚胺酯在室温下发生区域选择性的氮杂-曼尼希反应,实现异噁唑的不对称N—H烷基化,以中等至良好的收率(46%~83% yield)和较好的对映选择性(82%~92%ee)合成非环状的N,N′-缩酮。所有产物结构由^(1)H NMR,^(13)C NMR和HR-MS(ESI)确证,绝对构型通过X-射线晶体结构分析确定。

基于丙烯酸-N-琥珀酰亚胺酯共聚物交联剂的壳聚糖水凝胶的生物相容性研究

壳聚糖作为一种天然的氨基多糖,拥有良好的生物相容性和资源可再生性,但是较差的力学性能限制了其更广泛的应用。本研究以丙烯酸、N-乙烯基吡咯烷酮和丙烯酸-N-琥珀酰亚胺酯为单体聚合得到三元共聚物大分子交联剂,然后将其与壳聚糖溶液混合后制备壳聚糖水凝胶。采用红外、热重、SEM等对合成的聚合物及壳聚糖凝胶的组成、形貌和热稳定性进行了表征。结果表明,丙烯酸-N-琥珀酰亚胺酯共聚物的数均分子量为111900,具有一定的水溶性,与壳聚糖形成的水凝胶有良好的力学性能、溶胀性能和水蒸气渗透速率。在PBS(pH=7.4)中交联的凝胶膜与酸性条件下制备的凝胶膜相比,热分解温度提高,水接触角变大,力学性能得到较大提升。细胞毒性实验表明壳聚糖凝胶有良好的生物相容性,人脂肪干细胞在壳聚糖凝胶膜上会形成细胞簇并分泌外泌体。将壳聚糖凝胶膜覆盖在脂肪干细胞上,细胞能正常生长并分泌外泌体。因此,壳聚糖凝胶具有负载外泌体后应用于皮肤敷料的潜力。

Simple Detection Method of Biogenic Amines in Decomposed Fish by Intramolecular Excimer Fluorescence

Biogenic amines are known to have various biological functions such as not only neurotransmitter and cell proliferation but also food poisoning. Bacterially-decomposed amines such as histamine, agmatine, putrescine, cadaverine, spermidine and spermine cause allergic symptoms. We developed simple method for measurement of polyamine as indicator of food decomposition with a fluorometer by using 4-(1-Pyrene)butyric acid N-hydroxysuccinimide ester (PSE). PSE reacts with primary and secondary amino moieties of polyamines and produces the intramolecular excimer fluorescence. Excimer fluorescence with broad peak at around 470 nm was clearly detected in linear type biogenic amines such as putrescine, cadaverine, spermidine and spermine at 10 mM. However neither histamine nor trimethylamine altered the fluorescence. Decomposed sardine and mackerel by improper storage showed stronger intensity than fresh ones. Comparing with OPA-method, PSE method was useful for screening biogenic amines present in food, esp. fish since the analysis was simple after one-step purification procedure. An inexpensive system which can rapidly detect biogenic amines from food is necessary in a medium and small-sized food business. The technique using excimer has potential to realize the high through-put screening system for evaluation of food freshness and is expected to bring the public interests such as food security and safety of consumer.

A Novel Method for the Synthesis of Bioactive Benzimidazolyl-Phenoxyacetic Acid O-Acetylglucosyl Saccharide Esters

A novel method of synthesis of nitro or trifluoromethyl substituted benzimidazolyl phenoxyacetic acid O-acetylglucosyl saccharide esters by the reaction of O-acetylglucosyl bromide with substituted benzimidazolyl phenoxyacetic acid at room temperature was developed. 4 dimethylaminopyridine （DMAP） was used as catalyst, triethylamine （Et3N） was used as deacid reagent, three saccharide esters were synthesized in the system of DMAP/ Et3 N. The catalytic mechanism of DMAP/Et3N was discussed. The results show that DMAP is an effective catalyst, the yields can reach 50%. The test indicates that the title compounds show better antiplantviral activity.

An Alternative Synthesis and Crystal Structure Characterization of Nutrient Fortifier N-(1-(Phenylacetyl)-L-prolyl) Glycine Ethyl Ester

A nutritional fortifier N-(1-(phenylacetyl)-L-prolyl)glycine ethyl ester(4)was successfully synthesized through two synthetic schemes and characterized by IR,^1H-NMR,^13C-NMR,elemental analysis and X-ray single-crystal diffraction.The intermediate N-phenylacetyl-L-proline(2)was synthesized by the solid-liquid reaction of L-proline and phenylacetyl chloride directly.Compound 2(C13 H15 NO3,Mr=233.26)belongs to the orthorhombic system,space group P212121 with a=8.9468(3),b=9.3190(3),c=14.0453(4)A,V=1171.03(6)A^3,Z=4,Dc=1.323 g/cm^3,μ=0.773 mm^-1,F(000)=496.0,the final R=0.0313 and wR=0.0797 for all data.Compound 4(C17 H22 N2 O4,Mr=318.36)is of orthorhombic system,space group P212121 with a=6.5831(2),b=8.5536(2),c=28.9138(9)A,V=1628.11(8)A^3,Z=4,Dc=1.299 g/cm3,μ=0.763 mm-1,F(000)=680.0,the final R=0.0353 and wR=0.0816 for all data.

新型细胞调节性死亡Parthanatos参与子痫前期胎盘损伤的机制研究

目的:验证新型细胞调节性死亡Parthanatos在子痫前期(PE)胎盘中的发生情况,探讨抗氧化剂N-乙酰-L-半胱氨酸乙酯(NACET)对PE滋养细胞的保护作用。方法:胎盘样本选自行剖宫产手术的PE患者15例(PE组)和正常妊娠分娩的产妇15例(NP组),利用蛋白质免疫印迹(Western blot)、实时荧光定量PCR(qRT-PCR)、免疫荧光、透射电镜评估PE患者胎盘中Parthanatos的发生情况。通过细胞计数8(CCK8)、Western blot、免疫荧光、荧光探针分别验证二甲基胍(MNNG)及NACET(分别为对照组、MNNG处理组、MNNG+NACET处理组)对HTR8/Sveno细胞Parthanatos的诱导和抑制作用。结果:①与NP组胎盘相比,PE组胎盘多聚腺苷二磷酸(ADP)核糖基聚合酶1(PARP1)mRNA及蛋白的表达增高,多聚ADP核糖(PAR)累积增多,线粒体受损严重,凋亡诱导因子(AIFM1)核定位增加,差异均有统计学意义(P<0.05)。②与对照组相比,MNNG处理组表现为可以引起HTR8/Sveno细胞PARP1蛋白的表达增高,PAR累积增多,细胞内活性氧增多,线粒体膜电位下降,AIFM1核定位增加,差异均有统计学意义(P<0.05)。③与MNNG处理组相比,MNNG+NACET处理组中5μmol/L的NACET能够显著提高细胞的存活率;伴随PARP1蛋白表达降低和PAR蛋白累积减少、细胞内活性氧水平降低、细胞核内AIFM1蛋白表达量降低、线粒体膜电位升高,差异均有统计学意义(P<0.05)。结论:PE胎盘中Parthanatos水平显著升高,MNNG可显著诱导HTR8/Sveno细胞发生PARP1依赖性的细胞调节性死亡,而NACET能够有效抑制MNNG诱导的滋养细胞Parthanatos的发生,有望成为PE临床治疗的新靶点。

Chiral Separation of N-Benzoyl Phenylalanine Methyl Ester by Nonaqueous Capillary Electrophoresis

A successful chiral separation of N-benzoyl phenylalanine methyl ester has been achieved by nonaqueous capillary electrophoresis (NACE) using P-CD as chiral selector in formamide (FA). Some experimental parameters influencing the chiral separation such as concentration of P-CD, ionic strength and apparent pH (pH*) are discussed.

Synthesis and Characterization of 2-cetyl-3-20 keto acid(N-ethyl perfluorinated octyl sulfonamide) N-ethyl ester

2-Cetyl-3-20 keto acid（N-ethyl perfluorinated octyl sulfonamide） N-ethyl ester was synthesized by the reaction of N-ethyl-N-hydroxyethyl perfluorinated octyl sulfonamide and alky ketene dimer. The experimental results show that the yield of products can be 89% when the molar ratio of perfluorinated octyl sulfonamide to ketene dimer is 1 ： 1.1 and the reaction lasts about four hours at 80 ℃. The structure of the product was characterized by FTIR and ^1HNMR. The product can dissolve in polar solvents such as NMP, DMAC, THF, DMSO, CHCl3, and 10% weight-loss temperature measured by TGA is 202℃.

Chloroquine Relieves Acute Lung Injury in Rats with Acute Hemorrhagic Necrotizing Pancreatitis

Summary： This study preliminarily investigated the mechanism by which chloroquine （CQ） relieves acute lung injury （ALI） complicated in acute hemorrhagic necrotizing pancreatitis （AHNP）. Sixty male Wistar rats were randomized into sham-operated group （group A, n=10）, AHNP group （group B, n=10）, L-arginine-treated group （group C, n=10）, L-N-nitro-L-arginine methyl ester （NAME）-treated group （group D, n=10）, CQ-treated group （group E, n=10） and CQ＋L-NAME-treated group （group F, n=10）. TLR4 expression was measured by using real time-PCR and Western blotting respectively. The results showed that, in the group B, the expression of TLR4 and the levels of TNF-α and IL-6 in the lungs were significantly increased, and the nitric oxide （NO） concentration was reduced, as compared with those in the group A （P〈0.05 or P〈0.01）. Lung injury was aggravated with the increased expression of TLR4. When the inhibitor and stimulator of TLR4, namely L-Arg and L-NAME, were added respectively, lung injury was correspondingly relieved or aggravated （P〈0.05 or P〈0.01）. In the group E, TLR4 expres- sion was substantially lower and NO concentration higher than those in the group B （P〈0.05 or P〈0.01）. However, in the group F, NO concentration was markedly decreased, and the inhibitory effect of CQ on TLR4 expression and the relief of lung injury were weakened when compared with those in the group E （P〈0.05 or P〈0.01）. It was concluded that TLR4 may play an important role in the pathogenesis and development of ALl complicated in AHNP. CQ could relieve ALl by decreasing the TLR4 expression and increasing the NO release.

Studies on the esterifications of 9-(hydroxyimino)-4-methyl-8,9-dihydrofuro[2,3-h]chromen-2-one with acid chlorides under different conditions

The esterifications of 9-（hydroxyimino）-4-methyl-8,9-dihydrofuro[2,3-h]chromen-2-one （4） with acid chlorides afforded normal oxime-esters 3a-e in 35-78% yields in presence of excessive 4-dimethylaminopyridine as the acid scavenger, whereas the reactions gave unexpected 8-substituted products N-（8-chloro-4-methyl-2-oxo-2H-furo-[2,3-h]chromen-9-yl）amides （5a-c） and 4-methyl-2,9-dioxo-8,9-dihydro-2H-furo[2,3-h]chromen-8-ylcarboxyloates （6d-e） by using excessive acid chlorides. The structures of 10 new compounds were determined by 1H NMR, 13C NMR, MS and HRMS, and the possible mechanism for the formation of unexpected products 5a--c and 6d-e was also proposed.

Microwave-promoted solvent-free synthesis of N-(diphenylmethylene)glycine alkyl esters

The efficient synthesis of N-（diphenylmethylene） glycine alkyl esters was achieved for the first microwave irradiation under solvent-free condition, using PEG or quaternary ammonium salts as phase transfer catalysts （PTCs）. Under the optimum conditions, N-（diphenylmethylene） glycine alkyl esters were obtained in excellent yields in most cases.

STUDY ON THE SYNTHESIS AND PROPERTIES OF POLY(ESTER-IMIDEETHER)MULTIBLOCK COPOLYMERS

A new class of poly(ester-imide-ether) multiblock copolymers was synthesized by transes-terification and melt copolymerization of dimethyl terephthalate (DMT) and N-(4-carbomethoxyphenyl)-4-(carbomethoxy)-phthalimide with ethylene glycol (EG) and polytetramethylene glycol (PTMG). The structure of the above copolymers was characterized by H-1-NMR and IR spectroscopy. Some properties of the coplymers were also examined. It was found that their mechanical properties and heat stability, compared with poly(ether-ester) copolymers, were obviously improved.

金属/电催化NHPI烷基酯脱羧构筑碳-碳键研究进展

近年来,由于自由基反应在碳-碳键构筑中独特的作用,有机化学家相继开发了各种自由基前体化合物。N-取代丁二酰亚胺(NHPI)还原活性酯作为一种重要的自由基前体化合物,近期受到了有机化学家的广泛关注。本文综述了该领域的最新研究进展,主要介绍在电、金属催化条件下,自由基诱导N-取代丁二酰亚胺酯类化合物参与的碳-碳键构筑。

Pyrolysis-GC/MS of Menthyl Esters of N-Benzoxycarbonyl Amino Acid

With the aid of a Pyrolysis-GC/TOF MS technique, the pyrolysis behaviour of two menthyl esters of N-benzoxycarbonyl amino acid was investigated. A clear pattern emerges involving the cleavage of the bond linking the menthyl ring to the carboxy group, followed by further degradation of the fragments. The major pyroproducts were p-menth-l-ene pyrolysed at a higher temperature or p-menth-2-ene pyrolysed at a lower temperature, and various derivatives of cyclohexene pyrolyzed from the menthyl ring. In addition, some of the products were also iden- tified as derivatives of benzene from the pyrolysis of benzyloxyl moiety.

A new triterpene saponin from Panax japonicus C.A.Meyer var major(Burk.) C.Y.Wu et K.M.Feng

One new Iriterpene saponin was isolated from Panaxjaponicus C. A. Meyer var major （Burk.） C. Y. Wu et K. M. Feng, and established as oleanolic acid 3-O-[β-D-glucopyranosyl-（1 →2）-β-D-glucuronopyranosyl-6＇-O-n-butyl ester] which showed mod- erate antitumor activities against the A2780 cells and OVCAR-3 cells. Its structure was established by means of spectral data, particularly NMR, including HSQC and HMBC techniques.

Synthesis, Crystal Structure and Inhibition of N-2-Thiophenesulfonyl-α-L-phenylalanine Ethyl Ester on K562 Cell Proliferation

The title compound N-2-thiophenesulfonyl-a-L-phenylalanine ethyl ester has been synthesized. Complete assignments were achieved by IR, MS, ^1H NMR and single-crystal X-ray diffraction analyses. Using MTT assay, the inhibitory rate of the title compound on K562 cells （chronic myeloid leukemic cells） was measured and the result of preliminary bioassay showed that the title compound possesses antiproliferation effects on K562 cells. In order to investigate the relationship between structure and activity of the target compound, we report its crystal structure and biological behavior in the present paper. Crystallographic data： C15H17NO4S2, Mr = 339.42, monoclinic, space group P21, flack = -0.15（12）, a = 5.7916（10）, b = 11.5078（19）, c = 12.924（2） A, β = 97.781（3）°, Z = 2, V = 853.4（2） A^3, De = 1.321 g/cm^3, F（000） = 356, -7≤h≤7, -10≤k≤14, -15 ≤ l≤15, R = 0.0628, wR = 0.1540 and μ（MoKa） = 0.327 mm^-1. The molecule comprises a benzene and a thiofuran rings, and the intramolecular N（1）-H（1A）…O（1） makes a five-membered ring of O（1）--C（6）-C（5）--N（1）--H（1A）.

SnCl_2催化合成N,N-二乙基甘氨酸酯

对9种N,N-二乙基甘氨酸酯的合成进行了研究.以SnCl2作催化剂,N,N-二乙基甘氨酸分别与正己醇、正辛醇、正癸醇、正十二烷醇、正十四烷醇、正十六烷醇、香叶醇、香茅醇和1,6-己二醇在环己烷中回流反应合成了N,N-二乙基甘氨酸正己酯、N,N-二乙基甘氨酸正辛酯、N,N-二乙基甘氨酸正癸酯、N,N-二乙基甘氨酸正十二烷醇酯、N,N-二乙基甘氨酸正十四烷醇酯、N,N-二乙基甘氨酸正十六烷醇酯、N,N-二乙基甘氨酸香叶醇酯、N,N-二乙基甘氨酸香茅醇酯和N,N-二乙基甘氨酸-6-羟基-1-己酯,其结构经IR谱、1HNMR谱和ESI-MS谱确证.并考察了各因素对产物收率的影响,较佳的反应条件是:n(脂肪醇):n(N,N-二乙基甘氨酸):n(氯化亚锡)=1:1.2:0.09,在环己烷中回流2.5 h,产物的收率为89.3%～97.6%.