Application of microwave heating technique for rapid synthesis of ?,?-unsaturated esters

The use of microwave heating technique for the acceleration of ortho ester Claisen rearrangement (a three step transformation) is described. Irradiation of a DMF solution of the allyl alcohol 5, triethyl orthoacetate and propionic acid (catalytic) in an Erlenmeyer flask for 10 minutes in a microwave oven generated the ester 8 in 83% yield. Analogously, ortho ester Claisen rearrangement of a variety of allyl and propargyl alcohols (9, 12-22) were achieved. The formation of the diester 10 from 2-butyne-1,4-diol (9) via the ortho ester Claisen rearrangement of two allyl alcohol moieties (involving sh steps) in 15 minutes, demonstrates the versatility of the microwave heating technique.

Crystal Structures and Physicochemical Properties of Four New Lamotrigine Multicomponent Forms

In the present study, four new multicomponent forms of lamotrigine (LTG) with selected carboxylic acids, viz. acetic acid, propionic acid, sorbic acid, and glutaric acid, have been identified. Preliminary solid-state characterization was done by differential scanning calorimetry/thermogravimetric, infrared, and powder X-ray diffraction techniques. X-ray single-crystal structure analysis confirmed the proton transfer, stoichiometry, and the molecular composition, revealing all of these to be a new salt/salt-cocrystal/salt monosolvate monohydrate of LTG. All four compounds exhibited both the aminopyridine dimer of LTG (motif 4) and cation-anion dimers between protonated LTG and the carboxylate anion in their crystal structures. Further, these new crystal forms were subjected to solubility studies in water, powder dissolution studies in 0.1 N HCl, and stability studies under humid conditions in comparison with pure LTG base. The solubility of these compounds in water is significantly enhanced compared with that of pure base, which is attributed to the type of packing motifs present in their crystal structures as well as to the lowering of the pH by the acidic coformers. Solid residues of all forms remaining after solubility and dissolution experiments were also assessed for any transformation in water and acidic medium.

The physicochemical characteristics and anaerobic degradability of desiccated coconut industry waste water

Desiccated coconut industries (DCI) create various intermediates from fresh coconut kernel for cosmetic, pharmaceutical and food industries. The mechanized and non-mechanized DCI process between 10,000 and 100,000 nuts/day to discharge 6-150 m(3) of malodorous waste water leading to a discharge of 2646642 kg chemical oxygen demand (COD) daily. In these units, three main types of waste water streams are coconut kernel water, kernel wash water and virgin oil waste water. The effluent streams contain lipids (1-55 g/l), suspended solids (6-80 g/l) and volatile fatty acids (VFA) at concentrations that are inhibitory to anaerobic bacteria. Coconut water contributes to 20-50 % of the total volume and 50-60 % of the total organic loads and causes higher inhibition of anaerobic bacteria with an initial lag phase of 30 days. The lagooning method of treatment widely adopted failed to appreciably treat the waste water and often led to the accumulation of volatile fatty acids (propionic acid) along with long-chain unsaturated free fatty acids. Biogas generation during biological methane potential (BMP) assay required a 15-day adaptation time, and gas production occurred at low concentrations of coconut water while the other two streams did not appear to be inhibitory. The anaerobic bacteria can mineralize coconut lipids at concentrations of 175 mg/l; however; they are severely inhibited at a lipid level of = 350 mg/g bacterial inoculum. The modified Gompertz model showed a good fit with the BMP data with a simple sigmoid pattern. However, it failed to fit experimental BMP data either possessing a longer lag phase and/or diauxic biogas production suggesting inhibition of anaerobic bacteria.

Development of intermediate moisture marinated fish product and its storage characteristics

An attempt was made to prepare an intermediate moisture (around 44% moisture) marinated (pH around 4) fish product. Fillets from Sciaenid fish (each fish weighing 70-80 gm) were dipped in a solution containing 7% acetic acid, 20% common salt and 1% propionic acid for 2 hours. After soaking, the soaked fillets were partially dried to about 44% moisture. Three effective hurdles like low pH (by using 7% acetic add and 1% propionic acid), low water activity (by using 20% salt and partially drying the fillets) and preservative (1% propionic add), were used to prepare a shelf-stable product at room temperature. The dried product was sprayed with 0.0 5% BHA in 50% alcohol and further dried for 10 minutes to remove added water and alcohol, thereby another hurdle (preservative) against fat oxidation. The product was packed in 300 gauge polythene bags and stored in transparent screw cap plastic jars. Fortnightly samples were drawn and subjected to biochemical, bacteriological and organoleptic evaluation to study its storage characteristics. The product was in good acceptable form up to 4 months at ambient temperature. The product needed one hour soaking in water with two changes of water in between to make it free from excess salt and acid smell.

Opiate withdrawal induces dynamic-expressions of AMPA receptors and its regulatory molecule CaMKII alpha in hippocampal synapses

Adaptive changes in brain areas following drug withdrawal are believed to contribute to drug seeking and relapse. Cocaine withdrawal alters the expression of GluR1 and GluR2/3 subunits of alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) rec

特异性干扰肽对海马突触可塑性的影响及其功能研究

在哺乳动物复杂的神经网络中，突触是信息传递的枢纽，其突触传递效能的持续性变化被称为突触可塑性（synaptic plasticity）。长时程增强（long-term potentiation，LTP）和长时程抑制（long-term depression，LTD）现象是两种经典的突触可塑性形式，被视作学习和记忆可能的物质基础，得到了广泛地关注。其中，海马CA1区谷氨酸能突触处的LTP和LTD目前研究得最为广泛。 α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid（AMPA）受体作为介导兴奋性谷氨酸能突触基础传递的主要受体，是海马CA1区LTP和LTD正常表达的必要条件。近期的研究表明，AMPA受体通过胞吞、胞吐及侧向移动等方式在细胞膜和细胞内进行着持续地循环。因此，通过调节AMPA受体的上、下膜，进而影响突触后膜上AMPA受体的数量，便能对LTP和LTD产生影响。在本研究中，我们利用生物信息学的手段，以AMPA受体为靶点，设计出了旨在特异阻断LTP或LTD的多肽。运用离体脑片全细胞记录方式，在海马CA1区证明了干扰肽Pep-A2能够特异地阻断LTP而不影响LTD，Pep-A3能够特异地阻断LTD而不影响LTP。并初步探究了其关键的作用位点，为进一步理解LTP和LTD具体的分子机理打下了基础。成瘾作为异常的学习记忆过程，势必涉及到突触可塑性的变化。而特异性地阻断LTP和LTD，对药物成瘾效果的影响却鲜有报道（Wang YT，2007）。在另一部分工作中，我们采用穿膜肽Tat-A2和Tat-A3，在吗啡条件化位置偏爱（morphine conditioned place preference，morphine CPP）模型小鼠的测试前进行系统给药，结果发现两种干扰肽均能阻断或损伤其CPP的表达过程。这一现象，提示我们LTP和LTD在条件化位置偏爱的表达过程中都是不可或缺的，同时也为人们更好地理解成瘾过程的机理，及开发专一有效的治疗药物提供了新的思路。

5-氟尿嘧啶-β-环糊精结肠靶向前体药物的研究

5-氟尿嘧啶(5-Fluorouracil， 5-FU)是一种抗代谢药物，广泛用于临床治疗结直肠癌、胃癌、乳腺癌等多种癌症，但其首过代谢显著、亲脂性较低，选择性差、毒副作用大。为克服这些缺点人们对5-FU进行了大量的修饰工作，包括小分子修饰以及与各种载体形成微球、微囊、纳米粒、共价前药等。 环糊精(Cyclodextrin，简称CD)，可被结肠中的糖苷酶特异性地降解成小分子糖，而胃和小肠中由于缺乏相应的酶而使环糊精不被降解，这一特性在结肠药物的靶向输送及释放中有重要应用价值。环糊精中含有丰富的羟基，易进行化学修饰，将药物与环糊精通过共价键结合制成前药，使其在胃和小肠中不降解，而在盲结肠中被特异性的酶降解释出药物，达到结肠靶向释药的目的。研究表明，环糊精作为一种前药载体为结肠靶向释药和缓释、控释系统提供了一种有效的手段。 本工作选择5-氟尿嘧啶为模型药物、β-环糊精作为载体，通过中间体5-FU羧酸衍生物的制备及其与β-环糊精的偶联，合成了系列5-FU-β-CD前体药物，并利用紫外、红外、质谱、核磁、元素分析、热分析等手段对其进行结构表征。同时，还研究了前体药物的体外释药性质。具体内容包括： 1. 含有羧基的5-FU衍生物中间体的合成：(5-氟尿嘧啶-1-基)-乙酸(FUAC)、3-(5-氟尿嘧啶-1-基)-丙酸(FUPC)、5-(5-氟尿嘧啶-1-基)-戊酸(FUVC)的合成。 2. 中间体5-FU的羧酸衍生物与β-CD的偶联：分别通过以6-OTs-β-CD为中间体的取代法和活化酯法，合成了第一面取代和第二面取代的5-FU-β-CD大分子前体药物。在二面取代的前体药物制备中，通过改变原料的比例，合成了系列不同取代度(DS)的2-[(5-氟尿嘧啶-1-基)-乙酰基] -β-环糊精结合物。 3. 对上述前体药物进行体外释放研究：分别考察了前体药物在不同pH缓冲溶液中的水解行为及其在小鼠胃肠道人工体液中的酶解行为，并通过UV-Vis及HPLC对前体药物释放情况进行检测分析。 5-Fluorouracil(5-Fu), commonly known as a broad-spectrum antineoplastic drug, has been widely used in the treatment of various kinds of cancer including colon cancer for 40 years. However, this antitumor agent exhibits serious adverse effects, such as their marrow toxicity, gastrointestinal reaction and low selectivity in their clinical use. In order to improve its antitumor activity and reduce its toxicity, the compound was modified in various ways, including the formation of conjugated prodrugs with kinds of carrier, microsphere and nanoparticles etc. Cyclodextrins(CDs) are known to be barely capable of being hydrolyzed and only slightly absorbed in passing through the stomach and small intestine; however they are fermented into small saccharides by colonic microflora and thus absorbed as small saccharides in the large intestine. This biodegradation property of CDs may be useful as a colon-targeting carrier, and thus CD prodrugs may serve as a source of site-specific delivery of drugs to colon. It was demonstrated that prodrugs of CDs can provide a versatile means for construction of not only colon targeted delivery systems, but also delayed release systems. 5-Fluorouracil was taken as a model drug and β-CD as the carrier in this study. Series prodrugs of 5-FU was prepared through the preparation of reactive 5-FU derivatives containing carboxyl group and coupling to hydroxyl groups of CD. The structures of the conjugates were charactered by using IR, UV–vis, ESI-MS, 1H, 13C-NMR spectra, elemental analyses, and thermal analysis. In vitro hydrolysis behavior in aqueous solution and in rat gastrointestinal tract contents of the conjugates were also investigated. The main content of this dissertation includes following aspects: 1. The preparation of 5-FU derivatives containing carboxyl group: 5-Fluorouracil- acetic acid(FUAC)、3-(5-FU-1)-propionic acid (FUPC)、and 5-(5-FU-1)-valeric acid(FUVC). 2. The coupling of 5-FU derivatives to β-CD: 5-FU was selectively conjugated onto the primary or secondary hydroxyl groups of β-CD through an ester linkage, by the substitution of 6-OTs-β-CD and the activated ester method respectively. For the secondary face conjugation, the degree of substitution(DS) can be controlled by changing the mole ratio of the starting materials(FUAC and β-CD). 3. In vitro release behavior of the conjugates in aqueous solution and in rat gastro- intestinal tract contents of the conjugates were investigated, and the reaction was monitored and analyzed by using UV-Vis and HPLC methods.

Performance of palladium-containing supported catalysts in the oxidation of 1-butene

Performance of palladium-containing supported catalysts in the oxidation of 1-butene was investigated in a fixed-bed flow microreactor. The Pd-Fe-HCl/Ti-Al catalyst is the best among the five Pd-Fe-HCl/X (A = SiO2, gamma-Al2O3, Al-Ti, TiO2, MCM-22) catalysts for the oxidation of I-butene to butanone. It is interesting that high propionic acid selectivity can be obtained when V and H2SO4 are added to the palladium-containing supported catalysts.

A strategy for synthesis of ion-bonded amphiphilic miktoarm star copolymers via supramolecular macro-RAFT agent

Amphiphilic supramolecular miktoarm star copolymers linked by ionic bonds with controlled molecular weight and low polydispersity have been successfully synthesized via reversible addition-fragmentation chain transfer (RAFT) polymerization using an ion-bonded macromolecular RAFT agent (macro-RAFT agent). Firstly, a new tetrafunctional initiator, dimethyl 4,6-bis(bromomethyl)-isophthalate, was synthesized and used as an initiator for atom transfer radical polymerization (ATRP) of styrene to form polystyrene (PSt) containing two ester groups at the middle of polymer chain. Then, the ester groups were converted into tertiary amino groups and the ion-bonded supramolecular macro-RAFT agent was obtained through the interaction between the tertiary amino group and 2-dodecylsulfanylthiocarbonylsulfanyl-2-methyl propionic acid (DMP). Finally, ion-bonded amphiphilic miktoarm star copolymer, (PSt)(2)-poly(N-isopropyl-acrylamide)(2), was prepared by RAFT polymerization of N-isopropylacrylamide (NIPAM) in the presence of the supramolecular macro-RAFT agent. The polymerization kinetics was investigated and the molecular weight and the architecture of the resulting star polymers were characterized by means of H-1-NMR, FTIR, and GPC techniques. (c) 2008 Wiley Periodicals, Inc.

Effect of La3+ on structure and electrochemical reaction of microperoxidase-11 in imitated physiological solution

In this paper, the interaction mechanism between La3+ and microperoxidase-11 (MP-11) in the imitated physiological solution was investigated with the electrochemical and spectroscopic methods. It was found that when the molar ratio of La3+, and MP-11 is low, such as 2, La3+ can coordinate with oxygen in the propionic acid group of the heme group in the MP-11 molecule, forming the La-MP-11 complexes and leading to the increase in the non-planarity of the porphyrin cycle in the heme group and then the increase in the extent of exposure of the electrochemically active center, Fe(I I I) in the porphyrin cycle of the heme group. The increase in the extent of exposure of the electrochemically active center, Fe(III) in the porphyrin cycle of the heme group would increase the reversibility of the electrochemical reaction of the La-MP-11 complexes and its electrocatalytic activity for the reduction of H2O2. The results of the chromatographic analysis demonstrated that the average molar ratio of La3+ and MP-11 in the La-MP-11 complexes is 1.62.When the molar ratio of La3+ and MP-11 is high, such as 3, La3+ would shear some amino acid residues of the peptide of MP-11. Therefore, many La3+ ions can bind to the oxygen- and/or nitrogen-containing groups in the sheared amino acid residues except coordinating with the sheared and non-sheared MP-11 molecules.

Study on mechanism of interaction between Eu3+ and microperoxidase-11

The interaction mechanism between Eu3+ and microperoxidase-II (MP-11) in the aqueous solution was investigated using the UV-vis absorption spectroscopy, cyclic voltammetry and electrospray ionization mass spectrometry. It was found that one Eu3+ ion can coordinate with two carboxyl oxygen of two propionic acid groups of the heme group in the MP-11 molecule, leading the increase in the nonplanarity of the porphyrin ring and exposure degree of Fe(III) in the heme group. Therefore, the reversibility of the electrochemical reaction and the electrocatalytic activity of MP-11 for the reduction of oxygen are increased.

Resonance Raman spectroscopic study of cytochrome c mutants

The spectroscopic characteristics of cytochrome c(WT) and its mutants(Y67F and N521) in the low frequency region were studied by Resonance Raman technique. The results show that the replacement of phenylalanine for Tyr 67 in WT had a very slight effect on the hydrogen-bonding and conformation of the amino acid residues around propionic acid side chains of heme group. However, large effects on the hydrogen-bonding of internal water with its surrounding amino acid residues and hydrophobility of the home cavity were observed as Asn 52 was substituted with isoleucine, which resulted in conformational regulations of home group and surrounding amino acid residues.

Natural bromophenols from the marine red alga Polysiphonia urceolata (Rhodomelaceae): Structural elucidation and DPPH radical-scavenging activity

Three new natural occurring bromophenols, 3-(3-bromo-4,5-dihydroxyphenyl)-2-(3,5-dibromo-4-hydroxyphenyl)propionic acid (1), (E)-4-(3-bromo-4,5-dihydroxyphenyl)-but-3-en-2-one (2), and (3,5-dibromo-4-hydroxyphenyl) acetic acid butyl ester (3), together with one known bromophenol, 1,2-bis(3-bromo-4,5-dihydroxyphenyl)ethane (4), were isolated and identified from the marine red alga Polysiphonia urceolata. The structures of these compounds were elucidated by extensive analysis of ID and 2D NMR and IR spectra and MS data. Each of the isolated compounds was evaluated for scavenging alpha,alpha-diphenyl-beta-picrylhydrazyl (DPPH) radical activity and all of them exhibited significant activity with IC50 values ranging from 9.67 to 21.90 mu M, compared to the positive control, a well-known antioxidant butylated hydroxytoluene (BHT), with IC50 83.84 mu M. (C) 2007 Elsevier Ltd. All rights reserved.

三种海洋红藻和两株放线菌次级代谢产物研究

海洋是一个巨大的天然产物宝库，约占地球表面积70%的海洋蕴藏着80%的生物资源。由于海洋生态环境的特殊性，导致海洋生物能够产生大量结构独特多变和活性特殊多样的代谢产物。我国海域辽阔，海洋资源丰富，为寻找结构新颖、生理活性独特的先导化合物，加强对海洋资源的开发利用，本论文对中国沿海的三种海洋红藻和两株放线菌次生代谢产物以及生物活性进行研究，为新药研究与开发提供模式结构和药物前体。 对红藻似瘤凹顶藻Laurencia similis乙酸乙酯萃取物进行分离纯化，从中得到单体化合物35个，通过波谱学方法（IR、MS、NMR等）鉴定了他们的结构。分别为：2, 2, 5, 5, 6, 6-sixibromo-3, 3-bi-1H-indole (1)，3,5-dibromo- 1-methyl-indole (2)，3',5',6,6'-tetrabromo-2,4-dimmethyldiphenyl ether (3)，1,2,5- tribromo-3-bromoamino-7-bromomethylnaphthalene (4)，2,5,8-tribromo-3-bromo- amino-7-bromomethylnaphthalene (5)，2,5,6-tribromo-3-bromoamino-7-bromo- methylnaphthalene (6), 2,5,6,5',6'-pentabromo-3,4,3',4'-tetramethoxybenzophenone (7), (4E)-1-bromo-5-[(1'S*,3'R*)-3'-bromo-2',2'-dimethyl-6'-methylenecyclohexyl] -3-methylpent-4-ene-2,3-diol (8)，4-hydroxy-Palisadin C (9)，Isopalisol (10)，Luzonensol (11)，Palisadin B (12)，Aplysistatin (13)，Palisadin A (14)，5-Acetoxypalisadin B (15)，Aristolan-1(10)- en-9-ol (16)，Aristol-8-en-1-one (17)，Aristolan-9-en-1-one (18)，Aristolan-1(10)-en- 9-one (19)，Aristofone (20)，Aristolan-1(10)-8-diene (21)，Aristolan-1,9-diene (22)，10-Hydroxyaristolan-9-one (23)，7,11,15-trimethyl-3-methylene-hexadecan-1,2-diol (24)，3β-Hydroxyergosta- 5,24(28)-dien-7-one (25)，Isofucosterol (26)，β-sitosterol (27)，豆甾-4-烯-3α,6β-二醇 (28)，Cholesta-5-en-3β-ol (29)，Stigmasterol (30)，2,3,5,6-四溴-吲哚 (31)，2,3,6-tribromo-1H-indole (32)，3,5,6-tribromo-1-methylindole (33)，3,5,6-tribromo -1H-indole (34)，2,3,5-tribromo-1-methylindole (35)，其中化合物1-9为新化合物，化合物10-15、20和化合物24-30均为首次从该种海藻中得到。对新化合物1-9进行PTP1B酶抑制剂活性筛选，新化合物1、3、7显示强的PTP1B酶抑制活性。 对红藻齐藤凹顶藻Laurencia saitoi乙酸乙酯萃取物进行分离纯化，从中得到单体化合物11个，通过波谱学方法（IR、MS、NMR等）鉴定了他们的结构，分别为：2-hydroxyl-Luzofuranone (1)，2-hydroxyl-Luzofuranone B (2)，4-hydroxyl-Palisudin C (3)，2-bromo-γ-ionone (4)，Aplysistatin (5)，5-Acetoxypalisadin B (6)，Palisadin B (7)，Palisadin A (8)，Pacifigorgiol (9)，豆甾-4-烯-3α,6β-二醇 (10)，2, 3, 5, 6-四溴-吲哚 (11)，其中化合物1-4为新化合物，所有化合物均为首次从该种海藻中得到。通过MTT法对分离得到的新化合物1-4进行肿瘤细胞毒活性筛选，结果显示4个新化合物对所测肿瘤细胞株均无明显的活性。 对红藻瘤状软骨凹顶藻Chondrophycus papillous乙酸乙酯萃取物进行分离纯化，从中得到单体化合物5个，通过波谱学方法（MS、NMR等）鉴定了他们的结构，分别为邻苯二甲酸二丁酯 (1)，邻苯二甲酸二异辛酯 (2)，胆甾醇 (3)，3,7,11,15-tetramethyl-hexadec-2-en-1-ol (4)，4-羟基苯甲醛 (5)，所有化合物均为首次从该种海藻中得到。 对海洋放线菌M159乙酸乙酯萃取物进行分离纯化，从中得到单体化合物13个，通过波谱学方法（MS、NMR等）鉴定了他们的结构，分别为：5-(4',6'-dihydroxy-6-methyloctyl)furan-2(5H)-one (A)，phenethyl alcohol (1)，4-羟基苯甲醛(2)，anthranilic acid (3)，4-Hydroxy-3-methoxy- phenyl-propionic acid (4)，5-(6,7-dihydroxy-6-methyloctyl)furan-2(5H)-one (5)，p-Hydroxyphenylethyl alcohol (6)，3-Indoleacrylic acid (7)，Indol-3-carboxylic acid (8)，Adenine cordyceposide (9)，腺嘌呤核苷(10)，尿嘧啶核苷(11)，Thymidine (12)，其中化合物A为新化合物。所有化合物均为首次从该株放线菌中得到。 对海洋放线菌L211乙酸乙酯萃取物进行分离纯化，从中得到单体化合物15个，通过波谱学方法（MS、NMR等）鉴定了7个结构，分别为：spatozoate (1)，anthranilic acid (2)，3-Indolylethanol (3)，1-Acetyl-β-carbolin (4)，p-Hydroxyphen- ylethyl alcohol (5)，Indole-3-acetic acid (6)，Indol-3-carboxylic acid (7)，所有化合物均为首次从该株放线菌中得到。

Bromophenol derivatives from the red alga Rhodomela confervoides

Eight new bromophenol derivatives, 2,3-dibromo-4,5-dihydroxybenzyl methyl sulfoxide (1), 4-(2,3-dibromo-4,5-dihydroxyphenyl)-3-butene-2-one (2), 2-(3-bromo-5-hydroxy-4-methoxyphenyl)-3-(2,3-dibromo-4,5-dihydroxyphenyl)propionic acid (3), 2-(3-bromo-5-hydroxy-4-methoxyphenyl)-3-(2,3-dibromo-4,5-dihydroxyphenyl)propionic acid methyl ester (4), 2-phenyl-3-(2,3-dibromo-4,5-dihydroxyphenyl)propionic acid (5), 4'-methoxy-2",3',3"-tribromo-4",5',5"-trihydroxydiphenylacetic acid (6), and 3-bromo-5-hydroxy-4-methoxyphenylacetic acid (7) and its methyl ester (8), together with a known bromophenol, 3-bromo-5-hydroxy4-methoxybenzoic acid (9), were isolated from the red alga Rhodomela confervoides. Their structures were elucidated by spectroscopic methods including IR, EIMS, FABMS, ESIMS, HRFABMS, HRESIMS, 1D and 2D NMR, and single-crystal X-ray structure analysis. Compounds 1-4, 8, and 9 were found inactive against several human cancer cell lines and microorganisms.