局部麻醉药盐酸达克罗宁高效合成工艺

以对羟基苯乙酮和溴丁烷为起始原料,利用相转移催化剂通过两步反应合成药用级的盐酸达克罗宁。首先利用相转移催化剂催化生成中间体对丁氧基苯乙酮,再与哌啶盐酸盐、多聚甲醛反应生成产物。合成产物经1H-NMR和MS结构确证。结果表明,该反应总产率超过90%,简单易操作,适合工业生产。     

双氧水介导制备对硝基苯甲酸乙酯的初步研究（英文）

目的：探讨双氧水催化合成对硝基苯甲酸乙酯的可行性,并考察了反应物的摩尔比、催化剂用量、反应温度及反应时间对产物收率的影响。方法：分别采用单因素设计实验与正交设计实验,分析比较这两种方法的最佳反应条件。采用数字熔点仪测定样品的熔点;用GC112A型气相色谱仪测定了产物的纯度;用傅里叶变换红外光谱仪测定产物的结构。结果：双氧水可以作为合成对硝基苯甲酸乙酯的催化剂。综合分析可知：当无水乙醇和对硝基苯甲酸的摩尔比为4：1,催化剂含量为10%,反应温度为80℃,反应时间为2.5-3h时酯化产率可达到最高值。结论：双氧水催化对硝基苯甲酸、无水乙醇合成对硝基苯甲酸乙酯的效率较高,产品纯度高,环境污染小,不失为一种新的合成方法。     

双氧水介导制备对硝基苯甲酸乙酯的初步研究

目的:探讨双氧水催化合成对硝基苯甲酸乙酯的可行性,并考察了反应物的摩尔比、催化剂用量、反应温度及反应时间对产物收率的影响.方法:分别采用单因素设计实验与正交设计实验,分析比较这两种方法的最佳反应条件.采用数字熔点仪测定样品的熔点:用GC112A型气相色谱仪测定了产物的纯度;用傅里叶变换红外光谱仪测定产物的结构.结果:双氧水可以作为合成对硝基苯甲酸乙酯的催化剂.综合分析可知:当无水乙醇和对硝基苯甲酸的摩尔比为4:1,催化剂含量为10%,反应温度为80℃,反应时间为2.5-3h时酯化产率可达到最高值.结论:双氧水催化对硝基苯甲酸、无水乙醇合成对硝基苯甲酸乙酯的效率较高,产品纯度高,环境污染小,不失为一种新的合成方法.     

毕赤酵母表面展示南极假丝酵母脂肪酶B全细胞催化合成葡萄糖月桂酸酯

利用表面展示南极假丝酵母脂肪酶B(Candida antarctica lipase B,CALB)的毕赤酵母细胞为全细胞催化剂,以葡萄糖为酰基受体,月桂酸为酰基供体,在非水相体系中催化合成糖酯。用硅胶柱层析对产物进行初提,再用制备液相色谱进一步分离纯化,并用高效液相色谱-质谱鉴定纯品性质。对该酶法合成糖脂反应体系进行了优化,其中考察了有机溶剂种类、复合溶剂体系中二甲基亚砜(DMSO)体积百分比、酶量、底物摩尔比、水活度和温度等几个影响酯化反应的因素。结果表明:在5mL反应体系中,以叔戊醇/二甲基亚砜(DMSO30%,V/V)为反应介质,添加初始水活度为0.11的全细胞催化剂0.5g,葡萄糖0.5mmol/L,月桂酸1.0mmol/L,60°C下反应72h后,葡萄糖月桂酸单酯的转化率达到48.7%。     

生物可降解聚酯PBS的合成工艺研究

目的:为了提高1,4-丁二醇的附加值和开发新型的生物可降解材料.方法:以钛酸四丁酯为催化剂通过酯化缩聚合成了聚丁二酸丁二醇酯(PBS).考察了醇酸摩尔比、催化剂用量、反应温度、反应时间等因素对酯化率的影响.结果:醇酸物质的量比为1∶1.2,催化剂用量为0.6%(质量百分含量),反应温度220℃,反应时间6h,酯化率可达98.7%,平均分子量和分子量分布分别为:Mn=182197,Mw/Mn=1.626406.利用红外谱(IR)、凝胶渗透色谱(GPC)对产物进行了表征确认.     

氮杂环卡宾二氧化碳加合物催化转酯反应制备生物柴油

为了开发一种无金属有机催化剂用于生物柴油的制备,合成了一系列咪唑(啉)类氮杂环卡宾的二氧化碳加合物(N-heterocyclic carbenes CO2adducts,NHC-CO2),通过加热使其释放游离卡宾,并催化转酯反应制备生物柴油。为了比较催化活性,不同结构的NHC—CO2被用于大豆油的转酯反应中。结果发现:当使用咪唑类催化剂时,产物中甲酯含量大于90%,而当使用咪唑啉型催化剂,甲酯含量不足20%,这说明咪唑类催化剂更适合本研究中的转酯反应。催化剂最佳用量为大豆油的2%(摩尔百分比),最佳醇油比为12∶1。本研究中催化剂前体释放游离卡宾进入反应介质,反应迅速,产品分离简单,是制备生物柴油的有效绿色方法。     

酸性功能性离子液体催化合成二甘醇二苯甲酸酯

选用6种酸性功能化离子液体作为催化剂,催化苯甲酸和二甘醇酯化合成增塑剂二甘醇二苯甲酸酯(DEDB),通过实验考察反应温度、时间、催化剂种类及用量、原料投料比等工艺因素对合成收率的影响,确定了最佳反应条件:优选1-丁基磺酸-3-甲基咪唑对甲基苯磺酸盐([(CH_2)_4SO_3HMIm]TS)为催化剂,反应温度160℃,时间4.0 h,苯甲酸与二甘醇的摩尔比为2.2∶1,催化剂用量为二甘醇质量的10%,最终发现DEDB产率可达99.1%,且产品具有较高的品质。产物可以通过简单倾倒与离子液体催化剂分离,离子液体具有优异的重复使用性,使用10次后DEDB的产率仍有95.2%。     

天然杀虫剂β—水芹烯的合成

本文报导用环已烯经卤化反应、烷基化反应和Wittig反应合成天然杀虫剂β-水芹烯的方法。该合成方法原料易得,操作简便,反应条件温和,易于控制,适合于大量生产。中间体和产物经IR谱、~1HNMR谱、~(13)CNMR谱和MS分析证实了结构,产物总分离收率达38.37％。生物活性实验表明,产物对杂拟谷盗成虫具有较强的毒杀作用,LD_(50)=0.263μ1/头。     

具有转糖基活性的糖苷酶的分子进化

糖苷酶是糖类合成的重要催化剂,但其催化的反应为可逆反应,产物产量不高。近年来,通过糖苷酶催化位点氨基酸突变、其他位点氨基酸突变、随机突变、C端缺失突变和DNA混编（DNA shuffling）等方法对糖苷酶进行分子进化．使得糖苷酶合成糖类的产量大幅度提高,同时也优化了糖苷酶催化糖类合成时的其他性质,如区域选择性和温度耐受性等。     

微波辐射一步法合成香料富马酸二苄酯的研究

目的:在微波辐射下,以顺丁烯二酸酐和苄醇为原料,在复合催化剂对甲苯磺酸-硫脲存在下以甲苯为带水剂一步合成了富马酸二苄酯.方法:通过熔点测定和红外光谱分析对产物进行了结构表征.采用正交试验法研究了反应物的摩尔比、催化剂用量、反应温度、辐射反应时间等对产物收率的影响.结果:实验结果表明,在微波功率为700W,n(顺丁烯二酸酸酐):n(苄醇)=1:5,复合催化剂用量为总投料量的7%,甲苯20mL,一酯化、转化、二酯化的温度分别为140℃、145℃、135℃,回流分水90min的条件下,富马酸二苄酯的收率可达92.50%.结论:采用微波辐射法复合催化合成富马酸二苄酯具有操作简便、反应时间短、产物收率高等特点.     

Quantitation of benzo[a]pyrene-DNA adducts by postlabeling with 14C-acetic anhydride and accelerator mass spectrometry

Quantitation of carcinogen-DNA adducts provides an estimate of the biologically effective dose of a chemical carcinogen reaching the target tissue. In order to improve exposure-assessment and cancer risk estimates, we are developing an ultrasensitive procedure for the detection of carcinogen-DNA adducts. The method is based upon postlabeling of carcinogen-DNA adducts by acetylation with 14C-acetic anhydride combined with quantitation of 14C by accelerator mass spectrometry (AMS). For this purpose, adducts of benzo[a]pyrene-r-7,t-8-dihydrodiol-t-9,10-epoxide (BPDE) with DNA and deoxyguanosine (dG) were synthesized. The most promutagenic adduct of BPDE, 7R,8S,9R-trihydroxy-10S-(N(2)-deoxyguanosyl)-7,8,9, 10-tetrahydrobenzo[a]pyrene (BPdG), was HPLC purified and structurally characterized. Postlabeling of the BPdG adduct with acetic anhydride yielded a major product with a greater than 60% yield. The postlabeled adduct was identified by liquid chromatography-mass spectrometry as pentakis(acetyl) BPdG (AcBPdG). Postlabeling of the BPdG adduct with 14C-acetic anhydride yielded a major product coeluting with an AcBPdG standard. Quantitation of the 14C-postlabeled adduct by AMS promises to allow detection of attomolar amounts of adducts. The method is now being optimized and validated for use in human samples.     

Neuroexcitatory amino acids: 4-methylene glutamic acid derivatives

Summary A short synthesis of 4-methylene glutamic acid was achieved. Under thermal conditions the corresponding anhydride reacted with 2,3 dimethylbutadiene to afford the corresponding DIELS-ALDER adduct in good yield. L-4-methylene glutamic acid essentially acts on glutamate metabotropic receptors and is as potent as L-Glu in producing IPs.     

Durability improvement of wood by treatment with Methyl Alkenoate Succinic Anhydrides (M-ASA) of vegetable origin

Methyl Alkenoate Succinic Anhydride (M-ASA) is the product of the reaction between methyl esters of fatty acids and maleic anhydride. Crude M-ASA was synthesized from rapeseed oil methyl esters. The main compounds in this adduct are methyl oleate succinic anhydride (30%), methyl linoleate succinic anhydride (24%), unreacted methyl esters (41%) and unreacted maleic anhydride (4%). The treatment of wood at high temperature with crude M-ASA conferred protection against fungal decay and insects. Biological tests were carried out on Scots pine (Pinus sylvestris) sapwood and beech (Fagus sylvatica) according to European standards. M-ASA treatment was efficient against mould fungi (BS 3900), blue staining (EN 152), white and brown rot fungi (EN 113), longhorn beetle larvae (EN 46 and 47) and termites (EN 117). This treatment delayed the degradation of wood by soft rot (ENV 807) but it did not prevent it. Therefore, M-ASA combines all the necessary conditions to fulfil the requirements of the biological use classes 2 and 3, but not for class 4.     

Peptide synthesis using o-nitrophenylsulfenyl N-carboxy alpha-amino acid anhydrides. Sequential oligopeptides having alternate gamma-methyl L-glutamyl and L-phenylalanyl residues.

A series of sequential oligopeptides having the sequence alternating γ-methyl L -glutamyl and L -phenylalanyl residues have been successfully prepared by a rapid method involving the reaction of o-nitrophenylsulfenyl N-carboxy α-amino acid anhydrides with amino acid and peptide esters. The sequential oligopeptides, which are interesting from a conformational aspect, were obtained in optical pure forms above 74% yields. This result demonstrates that the o-nitrophenylsulfenyl N-carboxy α-amino acid anhydride method is especially useful for easy synthesis of protected oligopeptides with o-nitrophenylsulfenyl group.     

Responses to the major acrolein-derived deoxyguanosine adduct in Escherichia coli

Acrolein, a reactive alpha,beta-unsaturated aldehyde found ubiquitously in the environment and formed endogenously in mammalian cells, reacts with DNA to form an exocyclic DNA adduct, 3H-8-hydroxy-3-(beta-D-2'-deoxyribofuranosyl)-5,6,7,8-tetrahydropyrido[3,2-a]purine-9-one (gamma-OH-PdG). The cellular processing and mutagenic potential of gamma-OH-PdG have been examined, using a site-specific approach in which a single adduct is embedded in double-strand plasmid DNA. Analysis of progeny plasmid reveals that this adduct is excised by nucleotide excision repair. The apparent level of inhibition of DNA synthesis is approximately 70% in Escherichia coli DeltarecA, uvrA. The block to DNA synthesis can be overcome partially by recA-dependent recombination repair. Targeted G --> T transversions were observed at a frequency of 7 x 10(-4)/translesion synthesis. Inactivation of polB, dinB, and umuD,C genes coding for "SOS" DNA polymerases did not affect significantly the efficiency or fidelity of translesion synthesis. In vitro primer extension experiments revealed that the Klenow fragment of polymerase I catalyzes error-prone synthesis, preferentially incorporating dAMP and dGMP opposite gamma-OH-PdG. We conclude from this study that DNA polymerase III catalyzes translesion synthesis across gamma-OH-PdG in an error-free manner. Nucleotide excision repair, recombination repair, and highly accurate translesion synthesis combine to protect E. coli from the potential genotoxicity of this DNA adduct.     

A new, efficient, and simple method for the one-pot synthesis of alpha-acetoxyphosphonates from aldehydes under solvent-free conditions

A simple, efficient, and new method has been developed for the synthesis of alpha-acetoxyphosphonates from aldehydes through a one-pot reaction of aldehydes with diethylphosphite in the presence of acetic anhydride under solvent-free conditions using magnesium oxide. This method is easy, rapid, and high yielding for the one-pot synthesis of alpha-acetoxyphosphonates from aldehydes.     

Determination of hemoglobin adduct levels of the carcinogen 2,4-diaminotoluene using gas chromatography-electron impact positive-ion mass spectrometry

A procedure to determine hemoglobin adduct yields resulting from exposure to the carcinogen 2,4-diaminotoluene (2,4-TDA) was developed using gas chromatography-electron impact positive-ion mass spectrometry. Liberated 2,4-TDA was quantified following alkaline hydrolysis of hemoglobin. Optimized derivatization of free 2,4-TDA with heptafluorobutyric anhydride allowed detection of hemoglobin adduct levels as low as 5 ng/g Hb. Pure HFBA-2,4-TDA showed a linear dynamic range of 50 to 5000 pg. The quantitative extraction and recovery of liberated 2,4-TDA (ca. 100%) following hemoglobin hydrolysis allows accurate and precise determinations of adduct yields.     

Inhibition of protein and DNA synthesis in tissue culture cells by a derivative of methyl glyoxal and ascorbate

The inhibitory effect of a methyl glyoxal-ascorbate (MGA) adduct (NFCR 278021) on protein and DNA synthesis in monolayer cultures of GPK epithelial cells has been compared with the inhibitory action of methyl glyoxal (MG). GPK cells exhibited an ID₅₀ of 0.98 μM MG for both protein and DNA synthesis compared with an ID₅₀ of 0.92 mM for the adduct. Hill plots demonstrate that the characteristics of the receptor saturation are the same for MG and MGA, suggesting that the action of the two agents is mediated through the MG moiety which is modified by the presence of the ascorbate portion of the molecule in MGA. It is shown that MGA undergoes spontaneous oxidation in solution and is a substrate for ascorbate oxidase, but that no additional MG activity is released by total enzymic oxidation of MGA, and oxidised MGA possesses the same inhibitory characteristics as MGA. Inhibition of protein synthesis by ascorbate or dehydroascorbate were not demonstrated in the dose range employed for MGA. The inhibitory effect of the adduct on protein synthesis was found to be diminished in the presence of glutathione and glyoxalase I (Glo I) and II (Glo II).     

Translesion synthesis of acetylaminofluorene-dG adducts by DNA polymerase zeta is stimulated by yeast Rev1 protein

Translesion synthesis is an important mechanism in response to unrepaired DNA lesions during replication. The DNA polymerase ζ (Polζ) mutagenesis pathway is a major error-prone translesion synthesis mechanism requiring Polζ and Rev1. In addition to its dCMP transferase, a non-catalytic function of Rev1 is suspected in cellular response to certain types of DNA lesions. However, it is not well understood about the non-catalytic function of Rev1 in translesion synthesis. We have analyzed the role of Rev1 in translesion synthesis of an acetylaminofluorene (AAF)-dG DNA adduct. Purified yeast Rev1 was essentially unresponsive to a template AAF-dG DNA adduct, in contrast to its efficient C insertion opposite a template 1,N⁶-ethenoadenine adduct. Purified yeast Polζ was very inefficient in the bypass of the AAF-dG adduct. Combining Rev1 and Polζ, however, led to a synergistic effect on translesion synthesis. Rev1 protein enhanced Polζ-catalyzed nucleotide insertion opposite the AAF-dG adduct and strongly stimulated Polζ-catalyzed extension from opposite the lesion. Rev1 also stimulated the deficient synthesis by Polζ at the very end of undamaged DNA templates. Deleting the C-terminal 205 aa of Rev1 did not affect its dCMP transferase activity, but abolished its stimulatory activity on Polζ-catalyzed extension from opposite the AAF-dG adduct. These results suggest that translesion synthesis of AAF-dG adducts by Polζ is stimulated by Rev1 protein in yeast. Consistent with the in vitro results, both Polζ and Rev1 were found to be equally important for error-prone translesion synthesis across from AAF-dG DNA adducts in yeast cells.     

Preparative synthesis of C-(alpha-D-glucopyranosyl)-alkenes and -alkadienes: Diels-Alder reaction

The reaction of 2,3,4,6-tetra-O-benzyl-1-O-(p-nitrobenzoyl)-alpha-D-glucopyranose with (E)-penta-2,4-dienyltrimethylsilane and boron trifluoride etherate in acetonitrile afforded stereoselectively (E)-5-(tetra-O-benzyl-alpha-D-glucopyranosyl)-1,3-pentadiene in good yield. The readily available penta-O-benzoyl-alpha-D-glucopyranose reacted with allyltrimethylsilane in the presence of boron trifluoride etherate in acetonitrile to give 3-(tetra-O-benzoyl-alpha-D-glucopyranosyl)-1-propene and its beta anomer in yields of 60% and 2.3%, respectively. Diels-Alder cycloaddition of maleic anhydride to diene 1 afforded the adduct cis,cis-3-(tetra-O-benzyl-alpha-D-glucopyranosylmethyl)cyclohex -4-ene- 1,2-dicarboxylic anhydride in high yield.