核酸化学研究--Ⅰ.结晶的5′-O-三苯甲基和5′-O-单对甲氧三苯甲基核糖核苷-3′-磷酸盐

本文报导了采用单对甲氧三苯甲基氯或三苯甲基氯与3′-单核糖核苷酸直接反应的方法,合成的产物通过适当的溶剂处理获得了结晶的5′-O-单对甲氧三苯甲基保护的3′-胞核糖核苷酸、3′-尿核糖核苷酸、3′-腺核糖核苷酸以及5′-O-三苯甲基保护的 N-乙酰基-3′-鸟核糖核苷酸等化合物,既简化步骤、缩短时间,又提高了产物的纯度和得率.     

2′3′——不饱和核苷衍生物的固相合成

本文报道了用1％二乙烯苯交联的聚苯乙烯基磺酰氯树脂支载的5′-O-单-P-甲氧基-2′-脱氧-3′-磺酸酯胸苷在甲醇钠作用下进行酯的α,β-消除反应制备了较高产率的5′-O-单-P-甲氧基三苯甲基-2′,3′-双脱氧胸苷。     

生物素标记试剂的合成方法改进及其在DNA合成中的应用

以生物素,4,4’-二甲氧基三苯基氯甲烷,6-氨基-1-己醇,2-氰基乙氧基-双(N,N-二异丙基)亚磷酰胺等为原料,采用改进方法合成了生物素标记试剂——[1-N-(4,4’-二甲氧基三苯甲基)-生物素-6-氨基己基]-2-氰乙氧基-N,N-二异丙基亚磷酰胺(3),总收率51.0%,其结构经1H NMR,13C NMR,31P NMR和MS确证。通过固相亚磷酰胺三酯法,应用3合成了一段含有十个碱基的5’-端生物素标记的寡核苷酸链,其结构经MS确证。     

5′-O-三苯甲基核苷衍生物的微波合成

以DMF为溶剂,二甲氨基吡啶为碱,微波辐射下核苷衍生物与三苯甲基氯反应合成了8种选择性羟基保护的5′-O-三苯甲基核苷衍生物,收率67％～87％,其结构经^1H NMR和元素分析表征。     

5′-0-三苯甲基核苷衍生物的微波合成

以DMF为溶剂,二甲氨基吡啶为碱,微波辐射下核苷衍生物与三苯甲基氯反应合成了8种选择性羟基保护的5′-O-三苯甲基核苷衍生物,收率67%～87%,其结构经1H NMR和元素分析表征.     

抗肿瘤药物卡培他滨的合成工艺改进

本文以价廉易得的D-核糖为起始原料,经缩酮化保护、磺酰化,1,4-二氧六环做溶剂的条件下,使用硼氢化钾还原、再经水解、乙酰化反应得到关键中间体1,2,3-三-O-乙酰基-5-脱氧-D-呋喃核糖,再与5-氟胞嘧啶进行Silyl反应制备5′-脱氧-2′,3′-二-O-乙酰基-5-氟胞苷,与氯甲酸正戊酯进行酰胺化,水解得到目标化合物卡培他滨(1),结构经¹HNMR、¹³CNMR以及MS表征,总产率49.69%(以D-核糖计),HPLC测得纯度100.00%。该合成方法原料廉价易购、反应条件温和,改进后的路线操作简单,绿色环保,适合工业化生产。     

抗高血压药物维拉帕米的合成

以3,4-二甲氧基苯乙酸为原料,经酰化、脱水、C-烷烃化反应、得到关键中间体α-异丙基-3,4-二甲氧基苯乙腈（5）;再以3,4-二甲氧基苯乙酸为原料,经酰化、还原、N-烷烃化反应得到N-（γ-氯丙基）-N-甲基-3,4-二甲氧基苯乙胺（2）; 2与5经过缩合得到了最终产物维拉帕米,总收率为25.4%,其结构经¹H NMR和¹³C NMR确证。该合成路线具有原料廉价易得、操作简便、反应条件温和、后处理简便、收率较好等优点,具有较高的工业化前景。      

天然产物Combretastatin A-1和Combretastatin B-1的合成

基于Perkin反应策略合成了具有强效抗肿瘤、抗血管活性的天然产物Combretastatin A-1(CA1)和Combretastatin B-1(CB1).以2,3,4-三羟基苯甲醛(1)为起始物, 经单甲基化反应得到2,3-二羟基-4-甲氧基苯甲醛(2), 再经酚羟基保护得到2,3-二异丙基-4-甲氧基苯甲醛(3), 该化合物与3,4,5-三甲氧基苯乙酸(4)发生Perkin反应分离得到E-2-(3,4,5-三甲氧基苯基)-3-(2',3'-二异丙氧基-4'-甲氧基)丙烯酸(E-5), 经脱羧反应得到Z-3,4,4',5-四甲氧基-2',3'-二异丙氧基二苯乙烯(6), 最后经脱保护反应得到CA1.另外, 将E-2-(3,4,5-三甲氧基苯基)-3-(2',3'-二异丙氧基-4'-甲氧基)丙烯酸(E-5)脱去保护基得到E-2-(3,4,5-三甲氧基苯基)-3-(2',3'-二羟基-4'-甲氧基)丙烯酸(7), 该化合物经脱羧-异构化反应得到E-3,4,4',5-四甲氧基-2',3'-二羟基二苯乙烯(E-CA1), 最后经催化氢化得到CB1.     

卡培他滨的合成工艺改进

以D-核糖为起始原料经缩酮化、酯化、NaBH_4在DMSO与石油醚(1∶0.5∶1.5)还原、水解、无水醋酸钠催化酰化制备中间体(6a6b)与5-氟胞嘧啶进行Silyl反应制备同一构型的5′-脱氧-2′,3′-二-O-乙酰基-5-氟胞苷(7),(7)再与氯甲酸正戊酯进行酰胺化,最后水解去除乙酰基得到卡培他滨,总收率42.17%。HPLC纯度为99.81%。该新合成方法原料廉价易购、反应条件温和、操作简单,适合工业化生产。     

含氟苯并异噁唑衍生物的合成及活性研究

以2,4-二甲氧基苯胺为起始原料,通过乙酰化保护合成N-(2,4-二甲氧基苯基)乙酰胺(2),经傅克反应合成N-(4-羟基-2-甲氧基-5-丙酰基苯基)乙酰胺(3),3再与盐酸羟胺反应生成N-(4-羟基-5-(1-(羟基亚氨基)丙基)-2-甲氧基苯基)乙酰胺(4),4在DMF-DMA作用下生成N-(3-乙基-6-甲氧基...     

Synthesis of N,O-protected derivatives of 2′-O-methylcytidine and of 2′-O-methyl- and N1-methylguanosines

Using selective 3′,5′-O-tetraisopropyldisiloxane protection, N-acyl-2′-O-methyl derivatives of cytidine and guanosine and of 2′-O-tetrahydropyranyl-N₁-methylguanosine have been synthesized. It has been shown that the spatial screening of the amino groups by the neighboring methyl substituents in N₁-methylguanosine leads to its inactivation in acylation, tetrahydropyranylation, and tritylation reactions.     

The selective acylation of the functional groups of cytidine and 2′-deoxycytidine

A study has been made of the selective acylation of cytidine and 2′-deoxycytidine derivatives. It has been shown that selective 5′-O-acetylation of 2′,3′-O-isopropylidenecytidine occurs in aqueous solutions. An improved procedure for the 4-N-acetylation of 2′-deoxycytidine is described. The benzyloxycarbonyl, methoxyacetyl and phenoxyacetyl groups have been used to protect the 4-N-position of cytidine derivatives. The first of these could be removed by hydrogenolysis over Pd—C but the use of Pt as a catalyst resulted in reduction of the cytosine ring. The other two groups could be removed by mild acidic hydrolysis. The 4-N-position of 2′,3′-O-isopropylidinecytidine and of 2′-deoxycytidine could be selectively phenoxyacetylated by the use of 2,4-dinitrophenyl phenoxyacetate.     

Chemical alteration of nucleic acids and their components—XIII: Reaction of nucleosides with diacyl peroxides

Diacyl peroxides reacted at room tempt with cytidine and adenosine. The former gave 4-acyl and 3-oxido derivatives and the latter gave 6-acyl and 1-oxido derivatives. At 90°, diacetyl peroxide reacted with guanosine, adenosine, cytidine, and uridine by a homolytic process to give their C-methylated derivatives. The latter reaction was accelerated by the presence of a ferrous ion.     

Benzoylation of 2(3H)-benzothiazolones in the Presence of 8 Equivalents of Zinc Chloride in N,N-dimethylformamide

The use of the mixture of aluminum chloride-N,N-dimethylformamide 1,2 (AlCl 3 -DMF, 11:1) reagent in the Friedl-Crafts C acylation reaction of 2(3H)-benzothiazolones was previously reported. 3 These acylations reactions were found to proceed with high regioselectivity. The precise position of acylation was uniquivocally assigned by x-ray single-crystal defraction in the case of 6-benzoyl-2(3H)-benzothiazolone. 4 The assignment of the position of acylation was extended to other compounds by the use of high-field 1 H-NMR . 3     

Resolution of 2-aryloxy-1-propanols via lipase-catalyzed enantioselective acylation in organic media

2-Aryloxy-1-propanols, primary alcohols with an oxygen atom at the stereocenter, were resolved with good to high enantioselectivity by acylation with vinyl butanoate mediated by Pseudomonas sp. lipase in di-iso-propyl ether. Potential factors affecting the enantioselectivity of the enzymatic acylation were examined: solvents, acyl donors and temperature. Using this enantioselective acylation procedure, enantiomerically pure (R)-2-(4-chlorophenoxy)-1-propanol was prepared on a gram scale.     

Regioselective acylation of resveratrol catalyzed by lipase under microwave

The enzymatic regioselective acylation of resveratrol was achieved in organic solvents catalyzed by the lipase from Candida sp. 99–125 (CSL) under microwave irradiation. Influences of various reaction conditions have been studied. After selecting the optimum conditions [MTBE (20?ml, a_w?=?0.38), resveratrol (0.1?mmol), vinyl acetate (1.0?mmol) and CSL (100.0?mg) under microwave irradiation (35°C, 400 W)], CSL exhibited a satisfied enzyme activity (281?±?11?μmol/g/h) and yield of 75% for 4′-O-acetyl- resveratrol could be obtained in about 4?h when performing the reaction on a 25-fold-larger scale.

Schematic illustration of the enzymatic regioselective acylation of resveratrol catalyzed by the lipase from Candida sp. 99–125 (CSL) under microwave irradiation.     

在氯化亚锡存在下2,3-二甲基-2-丁烯与乙酐的催化酰化反应

一种新的催化剂,SnCl2·2H2O,已用于2,3-二甲基-2-丁烯与乙酐的酰化反应来制备高产率的3,3,4-三甲基-4-戊烯-2-酮 (TMP). 发现SnCl2·2H2O是室温下2,3-二甲基-2-丁烯与乙酐进行酰化反应的有效催化剂. 考察了催化剂用量、乙酐用量、反应时间和溶剂的加入等因素对该酰化反应的影响. 发现当催化剂/2,3-二甲基-2-丁烯摩尔比在0.30/1和 0.60/1之间、反应时间为2 h时,所得酰化产品的产率最高. 该酰化反应进行到完全所需的时间取决于催化剂用量和乙酐用量. 在需要加入溶剂的情况下,二氯甲烷或氯仿是一种合适的溶剂.     

Scandium triflate-catalyzed intramolecular Friedel-Crafts acylation with Meldrum's acids: insight into the mechanism

The intramolecular Friedel-Crafts acylation of arenes with Meldrum's acid derivatives catalyzed by Sc(OTf)₃ was reported as a mild and general entry into functionalized 1-indanones. Mechanistic investigations were undertaken to determine the rate-determining step in the acylation sequence using Meldrum's acid, as well as to examine the role of the Lewis acid catalyst. Enolizable Meldrum's acid derivatives react via an acyl ketene intermediate under thermal conditions, while quaternized Meldrum's acid derivatives are thermally stable and only act as effective Friedel-Crafts acylating agents in the presence of a Lewis acid catalyst. The acylation was postulated to proceed through direct acylation of a Lewis acid-activated carbonyl. In the catalytic Friedel-Crafts acylation of Meldrum's acids, triflic acid appeared to be the active catalytic species, with Sc(OTf)₃ serving as a very mild and convenient reagent for its delivery.     

Reactions of unsaturated acid halides—IV: Competitive friedel-crafts acylations and alkylations of monohalogenobenzenes by the bifunctional cinnamoyl chloride

Aluminium chloride-catalysed acylations and alkylations of monohalogenobenzenes with cinnamoyl chloride has been studied. Under strictly homogeneous conditions, alkylation was increasingly favoured relative to acylation as the primary reaction along the series: benzene <fluorobenzene<bromobenzene<chlorobenzene. Changing to heterogeneous conditions (excess catalyst with CS₂ as diluent) preserved this order but primary alkylation was relatively enhanced. The addition of nitrobenzene to the homogeneous reaction restrained alkylation more than acylation.Primary acylation may be followed by alkylation giving asymmetrical 1,3,3-triarylpropan-1-ones but the possibility that these are formed by alkylation followed by acylation is ruled out. These ketones may subsequently undergo α,β-ketonic fission.Primary alkylation may be followed by cycliacylation producing 3-arylindan-l-ones with the halogeno substituent at the side-chain aryl group and this observation rules out their alternative mode of formation, cyclialkylation of the primary acylation product.An example of a para → meta bromine shift is discussed.     

Synthesis and properties of analogs of 5(4)-aminoimidazole-4(5)-carboxamide and purines. 14. Acylation of 5(4)-aminoimidazole derivatives

The acylation of 5(4)-aminoimidazole derivatives was studied. It is shown that acylation by means of carboxylic acid anhydrides and chlorides takes place at the amino group, whereas acylation by means of chlorocarbonic acid esters takes place at the nitrogen atoms of the imidazole ring. Methods for the selective introduction of a carbomethoxy group in the 1, 3, and 5 positions of the 5(4)-aminoimidazole-4(5)-carboxamide molecule were developed.See [1] for communication 13.Deceased.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 2, pp. 247–252, February, 1984.