羟基化

Then Doripenem came into the market in the July ,2005. We studied the synthesis of Doripemen.Firstly, we synthesized the chemical 2 from the starting material------o-hydroxylphenylacylamine through Reformastky reaction, alkylation, Diekmann reaction, enolization, esterification and etc. Secondly, we synthesized the chemical 3 from L — hydroxylproline through the protection of carboxyl, amidogen and hydroxyl group, reduction by NaBr, SN_2 substitution and Mitsumobu reaction.

我们以水杨酰胺为起始原料，经Reformatsky反应、烷基化、Diekmann环合、烯醇化、酯化等反应合成双环母核2；再从L-羟基脯氨酸出发，经酯化保护羧基、保护氨基、保护羟基、硼氢化还原酯得醇、Sn2取代和Mitsumobu反应等合成巯基侧链3；最后由化合物3经脱保护、水解得硫醇，和化合物2在二异丙基乙基胺的作用下缩合，最后Pd／C催化脱保护，历经16步反应最终得到产物多尼培南。

Methods 4-Hydroxybenzonitrile (2) as the starting material was transformed to 4-hydroxy-thiobenzamide (3) via thioformylation. And ethyl 2-(4-hydroxyphenyl)-4-methylthiazole-5-carboxylate (4), which was synthesized via cyclization from 3, was treated with hexamethylenetetramine to generate the intermediate ethyl 2-(3-formyl-4-hydroxyphenyl)-4-methylthiazole-5-carboxylate (5). The target compound febuxostat (1) was obtained from 5 by etherification, cyanidation, hydrolysis.

以羟基苯腈为原料，经硫代甲酰化得到对羟基硫代苯甲酰胺(3)，3经环合得到2-（4-羟基苯基）－4-甲基－噻唑－5-羧酸乙酯(4)，4与乌洛托品反应，得到中间体2-（3-甲酰基－4-羟基苯基）－4-甲基－噻唑－5-羧酸乙酯(5)，之后再经醚化、氰化、水解得到目标产物(1)。

Goal compound synthesis namely: Take the vanillic acid as outset raw material, obtains 4- hydroxyl - 3- anisole methyl formate with the methyl alcohol reflux conditions, then after the etherification, the nitration, the return to original state, the ring closure response obtains 6- methoxy - 7- animal pen oxygen radical kui zuo lin - 4- alkone, then passes through the chlorination, the substitution aniline, to escape responses again and so on animal pen oxygen radical, etherification to obtain the goal compound; The goal compound and the diethylamine had the amine substitution reaction to obtain TM1, namely 4- benzene amino - 6- methoxy - 7- [2- hydroxyl - 3-(N, N- two ethyl aminos) third oxygen radical] kui zuo lin; Through zuo has the etherification with the Austria niter to respond obtains TM2, namely 4- benzene amino - 6- methoxy - 7- [2- hydroxyl - 3-(2- methyl - 5- nitryl imidazole) third oxygen radical] kui zuo lin.

目标化合物的合成即：以香草酸为起始原料，与甲醇回流条件下得到4-羟基-3-甲氧基苯甲酸甲酯，然后经过醚化、硝化、还原、环合反应得到6-甲氧基-7-苄氧基喹唑啉-4-酮，然后再经氯化、取代苯胺、脱苄氧基、醚化等反应得到目标化合物；目标化合物与二乙胺发生胺取代反应得到了TM1，即4-苯氨基-6-甲氧基-7-[2-羟基-3-丙氧基]喹唑啉；通过与奥硝唑发生醚化反应得到TM2，即4-苯氨基-6-甲氧基-7-[2-羟基-3-(2-甲基-5-硝基咪唑)丙氧基]喹唑啉。

Synthesis of target compounds namely: to vanillic acid as the starting material with methanol under reflux conditions for 4 - hydroxy -3 - p-methyl, then ether, and nitration, reduction, cyclization reaction 6 - methoxy -7 - benzyloxy-quinazoline -4 - one, and then by the chloride in place of aniline, benzyloxy-off, such as etherification reaction of the target compounds; target compounds with the second and third occurrence of substitution reactions of amines by the TM1, that is, 4 - amino-benzene -6 - methoxy -7 - [2 - hydroxy -3 -(N, N-diethyl amino) oxy c] quinazoline; with ether occurred Ornidazole reaction of TM2, namely, 4 - amino-benzene -6 - methoxy -7 - [2 - hydroxy -3 -(2 - methyl -5 - nitroimidazole) C oxy] quinazoline.

本论文以嘌呤类似物喹唑啉为母核，分别在其4位和7位引入结构多样的取代苯氨基和柔性侧链，设计了一系列4-取代苯胺基-6-甲氧基-7-(2-羟基取代丙氧基)喹唑啉类化合物。目标化合物的合成即：以香草酸为起始原料，与甲醇回流条件下得到4-羟基-3-甲氧基苯甲酸甲酯，然后经过醚化、硝化、还原、环合反应得到6-甲氧基-7-苄氧基喹唑啉-4-酮，然后再经氯化、取代苯胺、脱苄氧基、醚化等反应得到目标化合物；目标化合物与二乙胺发生胺取代反应得到了TM1，即4-苯氨基-6-甲氧基-7-[2-羟基-3-丙氧基]喹唑啉；通过与奥硝唑发生醚化反应得到TM2，即4-苯氨基-6-甲氧基-7-[2-羟基-3-(2-甲基-5-硝基咪唑)丙氧基]喹唑啉。

Ib was synthesized by condensation of phthalic anhydride with 2-methylresorcinol in fused AlCl〓/NaCl (5∶1), followed by selective acetylation, methylation, NBS bromination and condensation with sodium ethoxide.

邻苯二甲酸酐在熔融的三氯化铝-氯化钠(5：1)中和-2，6-二羟基甲苯环合得1，3-二羟基-2-甲基蒽醌〓后经选择性乙酰化、甲基化、NBS溴化、乙醇钠缩合得1-甲氧基-2-乙氧甲基-3-羟基蒽醌。

Furthermore, influences of different phosphate salts at various concentrations on the ionization efficiency of phosphopeptide were investigated systematically, finding that the signal intensity for phosphopeptide 48FQEEQQQTEDELQDK63 digested from β-casein were 5 to 8 times increased in an optimized condition with 10 mmol/L ammonium monobasic phosphate or 3 to 4 times increased with 10 mmol/L ammonium dibasic phosphate as additive to matrix 2,5-dihydroxybenzoic acid, respectively.

考察了两种适合于磷酸化肽离子化的基质类型2，5-二羟基苯甲酸和2，4，6-三羟基苯乙酮。用2，5-二羟基苯甲酸作为基质时，当加入10 mM 磷酸氢二铵时，磷酸化蛋白质β-casein的磷酸肽 48FQEEQQQTEDELQDK63的离子化效率可以增强5-8倍，当加入10 mM磷酸二氢胺时，磷酸肽的离子化效率可以增强3-4倍。

Itamin D from the skin and diet is metabolized in the lier to 25-hydroxyitamin D (Figure 1), which is used to determine a patient's itamin D status1,2,3,4; 25-hydroxyitamin D is metabolized in the kidneys by the enzyme 25-hydroxyitamin D-1-hydroxylase (CYP27B1) to its actie form, 1,25-dihydroxyitamin D.1,2,3,4 The renal production of 1,25-dihydroxyitamin D is tightly regulated by plasma parathyroid hormone leels and serum calcium and phosphorus leels.1,2,3,4 Fibroblast growth factor 23, secreted from the bone, causes the sodium–phosphate cotransporter to be internalized by the cells of the kidney and small intestine and also suppresses 1,25-dihydroxyitamin D synthesis.5 The efficiency of the absorption of renal calcium and of intestinal calcium and phosphorus is increased in the presence of 1,25-dihydroxyitamin D (Figure 1).2,3,6 It also induces the expression of the enzyme 25-hydroxyitamin D-24-hydroxylase (CYP24), which catabolizes both 25-hydroxyitamin D and 1,25-dihydroxyitamin D into biologically inactie, water-soluble calcitroic acid.2,3,4

从皮肤和食物来的维生素D在肝中代谢为25-羟基维生素D（图1），被用来决定病人体内维生素D情况的1，2，3，4；25-羟基维生素D在肾中被25-羟基维生素D1羟化酶（CYP27B1）转变为有活性的1，25-二羟基维生素D 。1，2，3，4由肾产生1，25-二羟基维生素D是被血浆甲状旁腺激素和血清钙，磷水平紧密调节。1，2，3，4由骨分泌的成纤维细胞生长因子23使钠磷协同转运蛋白被肾和小肠细胞内化及抑制1，25-二羟维生素D合成。5 在1，25-二羟基维生素D作用下肾和小肠吸收钙及磷的效率增高(图1)。2，3，6 它也包括25-羟四- 24 -羟化酶的表达(CYP24)，且将1，25二羟基维生素D和25羟基维生素D异化成无生物活性，水溶性的维生素D3-23羧酸。2，3，4

Two types of three-arm or four-arm star-shapedPCL-b-D,L-PLGA50 copolymer with high molecular weight and narrow molecularweight distribution were synthesized via the block copolymerization of MG monomerwith star-shaped hydroxy-terminated PCL as macroinitiator and 〓 as catalyst.

以端羟基化的三臂或四臂星型PCL聚合物为大分子引发剂、〓为催化剂，引发MG单体的嵌段共聚合，合成了高分子量和窄分子量分布的三臂或四臂星型PCL-b-D，L-PLGA50共聚物。

The results of FT-IR 1H-NMR indicate the structure of polyester, and the 13C-NMR analysis of three quaternary carbon showed the existing of hyperbranched struscture, MALDI-TOF MS showed the hyperbranched polyester structure, the degree of branching of the polyesters determined by 13C-NMR being 0.408. The esterification reaction kinetics followed a second-order equation and the reaction rate was controled by the concemtration of carboxyl group and hydroxyl group,-d/dt=K.

以IR、1H-NMR证实了聚酯结构的存在，13C-NMR谱图上3种季碳的特征峰有力证实了超支化分子结构的存在，MALDI-TOF MS证明了超支化聚酯的成功合成，并计算超支化聚酯的支化度为0.408；探讨并建立了超支化聚酯的缩聚反应动力学方程－d/dt=K，该缩聚反应属于二级反应，反应速率由羟基浓度和羟基浓度共同决定。

In this article the mechanism, synthesis process , application and development of the synthetic technology of nicotinic acid are introduced.

综述了烟酸的作用机理、合成工艺、应用及研究进展，从合成方法上看，一般分为试剂氧化法、氨氧化法、气相氧化法、电化学氧化法、生物氧化法和吡啶羟基化法等。

This one mode pays close attention to network credence foundation of the businessman very much.

这一模式非常关注商人的网络信用基础。

Cell morphology of bacterial ghost of Pasteurella multocida was observed by scanning electron microscopy and inactivation ratio was estimated by CFU analysi.

扫描电镜观察多杀性巴氏杆菌细菌幽灵和菌落形成单位评价遗传灭活率。