固体碱碱性位对丙酮和碳酸二甲酯反应的影响

考察了固体碱不同的碱性位对丙酮和碳酸二甲酯反应的影响,并对反应在不同碱性位上的反应机理进行了推测．实验结果表明,由表面羟基引起的弱碱位有利于丙酮自身缩合反应的进行,主产物为二丙酮醇、4-甲基-3-戊烯-2-酮和4-甲基4-戊烯-2-酮;Lewis酸碱离子对有利于碳酸二甲酯的甲基化反应的发生,主产物为2-甲氧基丙烯;而由固体碱表面配位不饱和的O^2-所造成的强碱位有利于碳酸二甲酯的甲氧基羰基化产物的生成,主产物为乙酰乙酸甲酯;同时发现各种产物的收率与对应的各碱性位的碱量之间均具有较好的线性关系．     

5-去氮嘌呤核糖核苷类似物的设计与合成研究进展

综述了近年来有关5-去氮嘌呤核糖核苷类似物作为潜在生物活性(如抗病毒、抗肿瘤等)先导化合物的设计与合成研究进展.指出该类先导物的设计与合成主要基于以下两种途径:一是在去氮嘌呤碱基的4-位或5-位引入不同的取代基;二是在去氮嘌呤碱基的4-位或5-位引入不同取代基的同时,对核苷中的糖基进行修饰.并从这两种途径着手介绍了近年来该领域所取得的主要研究进展.     

A3型Corrole中位取代基对其β位1H-NMR的影响

采用密度泛函(DFT)方法对八个中位有不同取代基的A3型corrole进行了几何结构优化和核磁共振(NMR)理论计算. 几何优化结果显示5,10,15-三苯基corrole的两个环内NH异构体的中位苯环空间排布方向不同. 此外, 虽然A3型corrole两个环内NH异构体A和B的能量相差不大, 但A和B分子的Boltzman分布概率却有较大的不同, 且受取代基影响很大. 因而在计算NMR时必须对A和B异构体的理论化学位移做Boltzman统计平均处理. NMR计算结果表明, 在B3LYP/6-311+G(2d,p)//B3LYP/6-31G(d,p)水平下可以得到较为合理的corrole的1H-NMR化学位移结果. β-位氢的化学位移与取代基Hammett常数σ+P的大小成正比关系. 此外, 由于corrole大环的低对称性, 取代基对不同位置β-位氢的NMR影响程度不同, 其β-位氢化学位移的大小和顺序与中位取代基的电子效应和corrole的立体结构因素有关.     

选择性氧化形成三对二硫键合成齐考诺肽

利用不同保护基保护的巯基的氧化反应性不同,分别以空气和碘作为氧化剂,通过选择性氧化工艺使齐考诺肽线性肽的1,8,16,20-位两对Trt保护巯基先形成两对二硫键,然后用碘氧化15,25-位Acm保护的巯基,成功地生成第三对二硫键,合成了齐考诺肽.     

A3型Corrole中位取代基对其β位^1H-NMR的影响

采用密度泛函(DFT)方法对八个中位有不同取代基的A3型corrole进行了几何结构优化和核磁共振(NMR)理论计算.几何优化结果显示5,10,15-三苯基corrole的两个环内NH异构体的中位苯环空间排布方向不同.此外,虽然A3型corrole两个环内NH异构体A和B的能量相差不大,但A和B分子的Boltzman分布概率却有较大的不同,且受取代基影响很大. 因而在计算NMR时必须对A和B异构体的理论化学位移做Boltzman统计平均处理.NMR计算结果表明,在B3LYP/6.311+G(2d,p)//B3LYP/6-31G(d,p)水平下可以得到较为合理的corrole的1H-NMR化学位移结果.β-位氢的化学位移与取代基Hammett常数σ-p的大小成正比关系.此外,由于corrole大环的低对称性,取代基对不同位置β-位氢的NMR影响程度不同,其β-位氢化学位移的大小和顺序与中位取代基的电子效应和corrole的立体结构因素有关.     

碘化钾在1,2-双(二溴甲基)苯及4位取代衍生物与反丁烯二腈反应中的作用

1,2-双(二溴甲基)苯及4位取代衍生物与反丁烯二腈在N,N-二甲基甲酰胺中反应12 h没有新的产物生成,在同样的条件下,加入碘化钾可使反应发生,主产物是2,3-二氰基萘及其6位取代衍生物,它的产率随加入的碘化钾的量不同而不同.当碘化钾的加入量相当于1,2-双(二溴甲基)苯及4位取代衍生物分子中溴的摩尔数,则1,2-双(二溴甲基)苯及其4位取代衍生物与反丁烯二腈基本作用完毕,反应产物主要是2,3-二氰基萘及其6位取代衍生物,产率87.1%.这个实验事实表明,碘化钾的作用机制不是传统意义上的催化剂而是一个反应试剂.据此,提出了上述反应的机理.     

1.6-缩水-2,4-二-氧-苄基-β-D-吡喃葡萄糖合成、开环及立体选择性成苷反应研究

以较好产率合成了3-位具有不同保护基的1,6-缩水-2,4-二-氧-苄基-β-D-吡喃葡萄糖, 并对其开环反应以及成苷反应的立体选择性进行了研究。     

1.6-缩水-2,4-二-氧-苄基-β-D-吡喃葡萄糖合成、开环及立体选择性成苷反应研究

以较好产率合成了3-位具有不同保护基的1,6-缩水-2,4-二-氧-苄基-β-D-吡喃葡萄糖,并对其开环反应以及成苷反应的立体选择性进行了研究.     

N~8-去氮-N~5-取代四氢叶酸类似物的设计合成及生物活性研究

以2,4-二氨基-6-羟甲基吡啶并[3,2-d]嘧啶为原料,在4-位氨基转换为羟基后与对氨基苯甲酰谷氨酸二乙酯连接生成叶酸类似物分子骨架,采用Adams催化方法还原吡啶环,在N5-位连接不同类型的取代基得到3个新的N8-去氮四氢叶酸类似物.经1H NMR,MS对化合物的结构进行了表征.初步生物活性结果表明,此类化合物对人重组二氢叶酸还原酶的抑制活性与N5-位的取代基有关联.     

7-位取代的甾体类化合物生物活性研究进展

7-位取代的甾体类化合物是一类具有良好生物活性的化合物,在抗炎、抗肿瘤等领域发挥着重要作用.本文以7-位取代的甾体类化合物为研究对象,按照不同的留体母核进行分类,对近年来有关7-位取代的甾体类化合物的生理活性研究进行综述,并为此类化合物的发展趋势和应用作了展望,以期为抗肿瘤药物的研发提供一定的理论基础.     

8-Methyl-7-substituted-1,6-naphthyridine-3-carboxylic acids as New 6-desfluoroquinolone antibacterials

1,6-Naphthyridine-8-methyl-7-substituted-3-carboxylic acids were synthesized as new 6-desfluoro-quinolone antibacterials in which the usual fluorine atom at C-6 position was replaced by an endocyclic nitrogen atom. Comparing the antibacterial activity of these 6-azaquinolones with our previous 6-amino and 6-hydrogen counterparts, they resulted always less active. However, the presence of methyl group at C-8 position ensure good Gram-positive antibacterial activity, with minimum inhibitory concentrations values on the same order of ciprofloxacin for piperidinyl derivative 3d and tetrahydroisoquinolinyl derivative 3c.     

Versatile routes to C-2- and C-6-functionalized glucose derivatives of iminodiacetic acid

A series of novel d-glucose derivatives, functionalized at the C-2 or the C-6 position with an iminodiacetic acid moiety for transition-metal complexation, has been prepared. The sugar and the metal-chelating parts are separated by either propyl or octyl chains and were introduced by the reaction of bromoalkylamine. Either N-1-Boc-3-bromopropylamine (17) or N-(8-bromooctyl)phthalimide (19) reacted with methyl 3,5,6-tri-O-benzyl-alpha-beta-d-glucofuranoside (4) (C-2 position) and 1,2:3,5-(O-methylene)-alpha-d-glucose (11) (C-6 position), respectively, in the presence of sodium hydride in DMF at room temperature, affording the desired intermediates. For aminopropyl derivatives, yields varied between 57% and 65%, and for aminooctyl derivatives, yields varied between 40% and 71%. After deprotection of the amine functionality, the metal chelate was built up by dialkylation (6a-c and 13a,b) with methyl bromoacetate in the presence of triethylamine under reflux in THF. Yields varied between 56% and 69% for the glucose modified at the C-2 position and between 58% and 62% for the one modified at the C-6 position. All compounds were characterized by 1H or 13C NMR or both, IR, and mass spectroscopy. Final products were isolated as a mixture of alpha and beta anomers.     

Structure and antitumor activity of the less-branched derivatives of an alkali-soluble glucan isolated from Omphalia lapidescens. (Studies on fungal polysaccharide. XXXVIII).

The structure and antitumor activity of Smith-type degradation products (OL-2-I, OL-2-II and OL-2-III) of an alkali-soluble glucan, OL-2, isolated from a crude fungal drug "Leiwan" (Omphalia lapidescens) were investigated. Methylation analysis suggested that OL-2-I was a (1----3)-beta-D-glucan with approximately one branch at every three main chain glucosyl units at each C-6 position; OL-2-II was a (1----3)-beta-D-glucan with approximately one branch at twenty four main chain glucosyl units at each C-6 position (number of all main chain glucosyl units is on average). OL-2-I, OL-2-II and OL-2-III which were Smith-type degradation products of OL-2, showed potent antitumor activity against the solid form of sarcoma 180 in ICR mice. These results indicated that the degree of beta-linked branching at position 6 was remarkably related to the antitumor activity.     

Effect of substituents on spin density in benzimidazole nitronyl nitroxide radicals studied by electron spin resonance

Several novel benzimidazole‐3‐oxide‐1‐oxyl radicals with substituents at 5 and/or 6 position were synthesized. The ESR analysis of nitrogen hyperfine coupling constants (hfccs) revealed that substituents at 5 and 6‐position affect the spin density to greater extent than substituents on the phenyl ring at 2‐position. Density functional theory calculations of nitrogen hfccs were performed using several different Pople type basis sets, as well as double and triple zeta quality individual gauge for localized orbital (IGLO‐II, IGLO‐III) and electron paramagnetic resonance (EPR‐II, EPR‐II) basis sets. Experimental and theoretical hfccs are compared. Copyright © 2009 John Wiley & Sons, Ltd.     

Synthesis of pyrrolo[2,3-d]pyrimidine-2,4-diones by sunlight photolysis of N-(5-vinyluracil-6-yl)sulfilimines

Uracil derivatives having a vinyl group at the C-5 position and a sulfilimine moiety at the C-6 position were prepared and cyclized to 1,3,6-trisubstituted pyrrolo[2,3-d]pyrimidine-2,4-diones by sunlight photolysis in good yields.     

Syntheses and surprising regioselectivity of 5- and 6-substituted decaboranyl ethers via the nucleophilic attack of alcohols on 6- and 5-halodecaboranes

The selective syntheses of new classes of decaboranyl ethers containing a range of functional groups substituted at the B5 or B6 positions were achieved through the reaction of alcohols with halodecaboranes. The surprising regioselectivity of the reaction, where the reaction of the 6-halodecaboranes (6-X-B(10)H(13)) with alcohols yielded the 5-substituted decaboranyl ethers (5-RO-B(10)H(13)) and the reaction with 5-halodecaboranes (5-X-B(10)H(13)) gave the 6-substituted decaboranyl ethers (6-RO-B(10)H(13)), was confirmed by NMR and X-ray crystallographic analyses. The crystallographic determinations also showed that the decaboranyl ethers had shortened B-O bonds and apparent sp(2) hybridization at oxygen indicating significant π-backbonding from oxygen to the cage boron. A possible substitution mechanism was computationally identified involving: (1) initial nucleophilic attack by the alcohol-oxygen at a site adjacent to the 5- or 6-halo-substituted boron, (2) movement of the terminal hydrogen at the point of attack to a bridging position, (3) formation of a 5-membered (B-O-H-Cl-B) cyclic transition state allowing the acidic methanolic-hydrogen to bond to the halogen, (4) release of HX, and finally (5) movement of a bridging hydrogen into the vacated terminal position. Deuterium labeling studies confirmed the movement of hydrogen from a bridging position of the halodecaborane into the halogen-vacated terminal position on the decaboranyl ether product. The relative reaction rates of the 6-X-B(10)H(13) compounds (X = F, Cl, Br, I) with alcohols were likewise found to be consistent with this mechanism.     

Syntheses of 6-O-ethyl/methyl-celluloses via ring-opening copolymerization of 3-O-benzyl-6-O-ethyl/methyl-α-d-glucopyranose 1,2,4-orthopivalates and their structure–property relationships

6-O-Alkyl-celluloses with well-defined ratio of ethyl and methyl groups at position 6 were prepared by ring-opening copolymerization of 6-O-ethyl and 6-O-methyl glucose 1,2,4-orthopivalate derivatives. An aqueous solution of 6-O-ethyl-cellulose having no methyl group was found to be thermo-responsive to be turbid at ~70 °C. An aqueous solution of 6-O-ethyl-cellulose with higher molecular weight showed endothermic and exothermic peaks in the heating and cooling curves of DSC measurements, respectively. However, 6-O-alkyl-cellulose having 10% methyl group lost its thermo-responsive character. 6-O-Alkyl-celluloses having more than ten percent of ethyl group at position 6 became water-soluble, though 6-O-methyl-cellulose is insoluble in water. Thus, 6-O-ethyl group was found to be of importance for the water solubility of regioselective 6-O-alkyl-celluloses. Furthermore, a small amount of methyl group introduced at C6 position was found to affect some of physical properties of 6-O-alkyl-celluloses such as thermo responsive property.     

O-Alkylation versus C-alkylation under Mitsunobu conditions

A comparative study of the Mitsunobu reaction at C1 and C6 positions of mannose using bis(2,2,2-trifluoroethyl) malonate as nucleophile is disclosed. While C-alkylation was predominant at the C6 position, only O-alkylation occurred at the anomeric position of the carbohydrate. Some factors playing a role in the selectivity of the reaction are discussed and an inverse mechanism of the Mitsunobu reaction for the anomeric position is proposed.     

Recherches sur le benzofuranne. LIX. Orientation de l'aroylation de l'éthyl-2 benzofuranne selon la nature du chlorure d'aroyle utilise

While both hindered and unhindered alkanoyl chlorides and some aroyl chlorides react with 2-ethylbenzofuran at the 3 position, most aroyl chlorides also react with 2-ethylbenzofuran at the 6 position and to a lesser extent at the 4 position.     

Mannich bases and methiodides of 6-(2-furyl)imidazo[2,1-b]thiazole and its substituted derivatives

The Mannich reaction in a number of 6-(2-furyl)-substituted imidazo[2,1-b]thiazoles is realized initially in the 5 position of the imidazothiazole system, whereas it is also realized in the 5 position of the furan ring in the presence of excess reagents if the latter position is not substituted. Iodomethylation occurs at the N₇ atom of imidazothiazole. The Mannich bases of 6-(5-nitro-2-furyl)imidazo[2,1-b]thiazole are iodomethylated only at the aminomethyl group. The pK_a values of the series of compounds were measured.