N2,N2,N6,N6-四乙基-4-醛基吡啶-2,6-二甲酰胺的合成

以2,6-二甲基吡啶为原料,经KMnO4氧化、二乙胺酰胺化、吡啶环自由基亲核取代反应得到N2,N2,N6,N6-四乙基-4-羟甲基吡啶-2,6-二甲酰胺,然后用Sarret试剂氧化得到标题化合物并探讨了氧化反应的最佳条件,产物结构经1HNMR、IR和MS得到表征.该产物是合成新型吡啶类有机配体的重要中间体.     

几种N-取代苯基马来酰亚胺单体的合成与表征

以马来酸酐、苯胺及其衍生物为主要原料合成了N-对甲苯基马来酰亚胺(NM PM I)、N-对氯苯基马来酰亚胺(NCLPM I)、N-对甲氧苯基马来酰亚胺(NM OPM I),产率可达85%以上。采用1H-NM R,13C-NM R和FT-IR等仪器对产物及中间产物马来酰胺酸的结构进行详细的表征。研究发现马来酰胺酸和马来酰亚胺苯环上不同的取代基,在1H-NM R谱图中,对HC=CH上质子峰的影响不大,而对苯环上质子峰却有影响,吸(供)电子基使苯环质子的化学位移向低(高)场移动;在13C-NM R谱图中,含强电负性(O、N、C l)的取代基使苯环上δc1低场移动,邻对位δc略向高场移动,取代基的电负性越大,位移也越大。     

酸性青莲4BNS催化氧化清洁生产工艺的研究

以N-乙基-N-(3'-磺酸基苄基)苯胺和甲醛为原料进行缩合反应,生成的隐色体在催化剂的作用下用过氧化镁氧化,氧化产物继续与N,N-二乙基苯胺进行二次缩合反应,经盐析干燥后得到酸性青莲4BNS。     

含氟取代基的β-二亚胺化合物的合成

以乙酰丙酮和氟代苯胺为原料,等摩尔量的对甲苯磺酸为催化剂,高收率地制备了6种芳环上含氟取代基的N,N-二芳基-2,4-戊二亚胺化合物(β-二亚胺),其中5种未见文献报道.产物通过1HNMR、IR和元素分析进行表征.     

嘧啶与联苯胺类共聚物的合成及表征

采用NaClO氧化联苯二胺成功合成了N,N′-二氯苯醌二亚胺、3,3′-二甲基-N,N′-二氯联苯醌二亚胺和3,3′-二甲氧基-N,N′-二氯联苯醌二亚胺,将其分别与4,6-二氯嘧啶采用金属配合物催化法共聚合,合成了3种新型共聚物:聚(N,N′-二氯联苯醌二亚胺-嘧啶)、聚(N,N′-二氯-3,3′-二甲基联苯醌二亚胺-嘧啶),聚(N,N′-二氯-3,3′-二甲氧基联苯醌二亚胺-嘧啶)。采用傅里叶变换红外光谱、紫外-可见吸收光谱、循环伏安、充放电对共聚物进行结构与性能测试。结果表明:该类共聚物具有一定的电化学活性,每种共聚物均在-0.2~1.0 V出现一对氧化还原峰;聚(N,N′-二氯苯醌二亚胺-嘧啶)、聚(N,N′-二氯-3,3′-二甲基联苯醌二亚胺-嘧啶,聚(N,N′-二氯-3,3′-二甲氧基联苯醌二亚胺-嘧啶)的比电容分别为46.2,34.4,23.9 F/g。     

双(2-二甲基氨基乙基)醚的制备及分离

在氮气保护下,加热N,N-二甲基乙醇胺和浓硫酸,使N,N-二甲基乙醇胺分子间脱水得到双(2-二甲基氨基乙基)醚。考察了反应时间、反应温度、浓硫酸的用量对产物收率的影响;最佳反应条件为:200~210℃,4~5 h,物料摩尔投料比为:n(浓硫酸)∶n(N,N-二甲基乙醇胺)=3.0∶1.0。用新型分离装置对反应液进行分离后,经减压精馏得到双(2-二甲基氨基乙基)醚[w(双(2-二甲基氨基乙基)醚≥98%],其收率为55.6%(以N,N-二甲基乙醇胺)。     

N-硝基-N-(2,6-二硝基-4-三氟甲基苯基)脲衍生物的合成及除草活性

以2,6-二硝基-4-三氟甲基氯苯为起始原料,与氨水反应生成2,6-二硝基-4-三氟甲基苯胺;该苯胺与乙酰硝酸酯反应生成N-硝基-2,6-二硝基-4-三氟甲基苯胺;以三乙胺为缚酸剂,N-硝基-2,6-二硝基-4-三氟甲基苯胺与固体光气在二氯甲烷中反应,生成酰氯中间体;酰氯中间体再与取代苯胺反应得到了7种含N-硝基的不对称脲类化合物。产物经IR1、HNMR、质谱、元素分析表征。对目标化合物进行了除草生物活性测试,初步测试结果表明:当其水溶液质量浓度为500 mg/L时,脲基另一端的苯环为2-氯苯基、4-氯苯基、2-甲基苯基、4-甲基苯基时,这些化合物对稗草的校正根长抑制率和校正茎长抑制率都大于40%;但这些化合物对苋菜作用不明显,对苋菜的校正根长抑制率和校正茎长抑制率小于20%。     

新型蓖麻油基季铵盐的合成及其抑菌性能研究

以蓖麻油酸甲酯为起始原料,与N,N-二甲基-1,3-丙二胺和溴化苄、溴乙烷通过酰胺化反应和季铵化反应生成了新型蓖麻油基季铵盐,其结构经FTIR、1HNMR、13CNMR及ESI-MS进行了确证。采用抑菌圈直径法对目标产物的抑菌性能进行了测试,结果表明,两种季铵盐均有一定的抑菌活性,N,N-二甲基-N-乙基-蓖麻油酸酰胺丙基溴化铵的抑菌活性略强于N,N-二甲基-N-苄基-蓖麻油酸酰胺丙基溴化铵。     

双（2-甲基氨基乙基）醚的制备及分离

在氮气保护下,加热N,N-二甲基乙醇胺和浓硫酸,使N,N-二甲基乙醇胺分子间脱水得到双（2-二甲基氨基乙基）醚。考察了反应时间、反应温度、浓硫酸的用量对产物收率的影响;最佳反应条件为：200-210℃,4～5h,物料摩尔投料比为：行（浓硫酸）：n（N,N-二甲基乙醇胺）-3．0：1．0。用新型分离装置对反应液进行分离后,经减压精馏得到双（2-二甲基氨基乙基）醚[w（双（2-二甲基氨基乙基）醚≥98％],其收率为55．6％（以N,N-二甲基乙醇胺）。     

循环伏安法研究显影剂的电化学行为

本文用循环伏安法对几种显影剂及其类似物DEPPD、DEPAP和TEPPD的电化学进行了研究。实验结果证明,DEPPD经一步氧化成醌二亚胺(QDI),而TEPPD则分两步氧化;DEPAP在pH<7时一步氧化成醌亚胺(QMI),pH>7时分两步氧化。在碱性条件下,各氧化产物可发生明显的脱氨反应。由实验测得的E 1/2与pH的关系,估算了它们的去质子化常数。     

以( )-脱氢枞胺为原料合成( )-弥罗松酚

报道了以(+)-脱氢枞胺为起始原料,通过两条路线合成生物活性的二萜化合物(+)-弥罗松酚。路线(1):(+)-脱氢枞胺在羟氨-O-磺酸和氢氧化钠作用下还原脱氨生成脱氢松香烷,再经Friedele-Crafts乙酰化、BaeyerVilliger氧化、水解生成(+)-弥罗松酚,总产率29.5%。路线(2):(+)-脱氢枞胺还原脱氨,然后与过氧化邻苯二甲酰反应得到(+)-弥罗松酚,总产率31.9%。     

The synthesis and crystal structure of unsubstituted 4,4-difluoro-4-bora-3a,4a-diaza-s-indacene (BODIPY)

The fully unsubstituted 4,4-difluoro-4-bora-3a,4a-diaza-s-indacene (BODIPY) was synthesized for the first time by oxidation of dipyrromethane followed by treatment with boron trifluoride diethyl etherate in the presence of a base. The compound was fully characterized and its X-ray crystal structure is reported.     

Monoamine Oxidase (MAO) Inhibitory Activity: 3‐Phenylcoumarins versus 4‐Hydroxy‐3‐phenylcoumarins

Monoamine oxidase (MAO) is a useful target in the treatment of neurodegenerative diseases and depressive disorders. Both isoforms, MAO‐A and MAO‐B, are known to play critical roles in disease progression, and as such, the identification of novel, potent and selective inhibitors is an important research goal. Here, two series of 3‐phenylcoumarin derivatives were synthesized and evaluated against MAO‐A and MAO‐B. Most of the compounds tested acted preferentially on MAO‐B, with IC₅₀ values in the micromolar to nanomolar range. Only 6‐chloro‐4‐hydroxy‐3‐(2’‐hydroxyphenyl)coumarin exhibited activity against the MAO‐A isoform, while still retaining good selectivity for MAO‐B. 6‐Chloro‐3‐phenylcoumarins unsubstituted at the 4 position were found to be more active as MAO‐B inhibitors than the corresponding 4‐hydroxylated coumarins. For 4‐unsubstituted coumarins, meta and para positions on the 3‐phenyl ring seem to be the most favorable for substitution. Molecular docking simulations were used to explain the observed hMAO‐B structure–activity relationships for this type of compound. 6‐Chloro‐3‐(3’‐methoxyphenyl)coumarin was the most active compound identified (IC₅₀=0.001 μM ) and is several times more potent and selective than the reference compound, R‐(?)‐deprenyl hydrochloride. This compound represents a novel tool for the further investigation of the therapeutic potential of MAO‐B inhibitors.     

Interaction of a hindered piperidine stabilizer with hydroxy-substituted aromatic carbonyl compounds in the photostabilization of polypropylene

The effect of a hindered piperidine compound, Bis[2,2,6,6-tetramethyl-4-piperidinyl] sebacate on the photostability and light-stabilizing performance of hydroxy-substituted benzophenone and anthraquinone compounds in polypropylene film has been examined using three different light exposure units. The stabilizing effects observed were found to be highly dependent on the utraviolet content (300–340 nm) of the light source. In the absence of this utraviolet component the hindered piperidine compound inhibited the photolysis of all the hydroxy-substituted compounds, whereas in its presence no protective effect was observed. In fact, direct absorption of ultraviolet light was found to be totally ineffective in photostabilizing the polymer. The protective effects were associated with the ability of the hindered piperidine compound to destroy the hydroperoxides formed during processing. This was confirmed by the observation of no protective action with unsubstituted benzophenone and anthraquinone through both steady-state and laser flash-photolysis experiments. A further novel protective effect was observed when the hindered piperidine molecule was linked to the anthraquinone chromophore in the 2-position to the carbonyl group. In this case photoprotection is associated with an intramolecular excited-state quenching process.     

C6‐Unsubstituted Pyrazolo[3,4‐d]pyrimidines Are Dual Src/Abl Inhibitors Effective against Imatinib Mesylate Resistant Chronic Myeloid Leukemia Cell Lines

Docking simulations were used to predict the most favorable interaction between the T315I mutated form of Abl (invariably associated with resistance to the tyrosine kinase inhibitor imatinib mesylate, IM) and C6‐unsubstituted and substituted pyrazolo[3,4‐d]pyrimidines previously found to be dual Src/Abl inhibitors. Two C6‐unsubstituted ( 1 and 2 ) and eight C6‐substituted compounds ( 3 – 10 ) were selected and assayed for their effects on the Ba/F3 cell line transducing the wild‐type p210Bcr–Abl construct, which is IM‐sensitive, or three of the most common mutations associated with IM resistance in vivo (T315I, Y253F, and E255K), and driven to drug resistance by saturating doses of IL‐3 or by the expression of the Bcr–Abl construct coding for the p185 protein of acute lymphoblastic leukemia. Compounds 1 and 2 were active against all cell lines assayed (LD₅₀ range: 0.7–4.3 μM ), whereas C6‐substituted compounds exhibited lower activity (LD₅₀～8 μM for compound 3 toward the T315I mutant). Notably, 1 and 2 were also effective toward the T315I mutation, which is insensitive to dual Src/Abl inhibitors. The cytotoxic effects of 1 and 2 on IM‐sensitive and IM‐resistant Ba/F3 cells were attributable, at least in part, to their pro‐apoptotic activity. Taken together, such findings suggest that C6‐unsubstituted pyrazolo[3,4‐d]pyrimidines may represent useful inhibitors to target IM‐resistant chronic myeloid leukemia.     

Quantitative structure-property relationships of new benzoxazines and their electrooxidation as a model of metabolic degradation

The quantitative structure-property relationships study of 40 benzoxazines, that seem to be very promising antimycobacterial drugs, allowed proposing and testing of the equations describing effects of substituents on half-wave potentials of these compounds. Although two structural types of benzoxazines were studied (i.e. thioxobenzoxazinones and benzoxazinedithiones), it is possible to describe the effect of substituent on half-wave potentials of benzoxazines by one general equation. A good correlation for relationship between half-wave potential and energy of HOMO orbital was also found.The study of electrochemical oxidation of these compounds as a model of their possible metabolic degradation was performed. It was possible to propose general scheme of electrochemical oxidation of sulfur containing benzoxazine derivatives. From the metabolic point of view, desulfuration is the corresponding process to this pathway. As these derivatives were not examined in vivo, obtained results represent very beneficial clues, and, moreover, proposed scheme could serve as a support for the explanation of strong antimycobacterial activity of sulfur containing benzoxazines.     

Redox properties and bond dissociations energies of phenoxyl radicals

Reduction half-wave potentials of several phenoxyl radicals have been measured by photomodulated voltammetry in acetonitrile. Two of the investigated radicals exhibit a reversible behavior, but for the others a rather quasi-reversible nature of the heterogeneous electron transfer has to be considered. The measured reduction half-wave potentials are within 70 mV of reported values for formal one-electron potentials of the phenolate-phenoxyl couples. That is why one can assume that the values of half-wave reduction potentials are close to the standard potentials of the electrochemical reactions. Differences of the bond dissociation energy (BDE)(OH), for the substituted phenols relative to the BDE(OH) of the phenol were calculated and compared with corresponding data in the gas-phase.     

Why Monoamine Oxidase B Preferably Metabolizes N-Methylhistamine over Histamine: Evidence from the Multiscale Simulation of the Rate-Limiting Step

Histamine levels in the human brain are controlled by rather peculiar metabolic pathways. In the first step, histamine is enzymatically methylated at its imidazole N^τ atom, and the produced N-methylhistamine undergoes an oxidative deamination catalyzed by monoamine oxidase B (MAO-B), as is common with other monoaminergic neurotransmitters and neuromodulators of the central nervous system. The fact that histamine requires such a conversion prior to oxidative deamination is intriguing since MAO-B is known to be relatively promiscuous towards monoaminergic substrates; its in-vitro oxidation of N-methylhistamine is about 10 times faster than that for histamine, yet this rather subtle difference appears to be governing the decomposition pathway. This work clarifies the MAO-B selectivity toward histamine and N-methylhistamine by multiscale simulations of the rate-limiting hydride abstraction step for both compounds in the gas phase, in aqueous solution, and in the enzyme, using the established empirical valence bond methodology, assisted by gas-phase density functional theory (DFT) calculations. The computed barriers are in very good agreement with experimental kinetic data, especially for relative trends among systems, thereby reproducing the observed MAO-B selectivity. Simulations clearly demonstrate that solvation effects govern the reactivity, both in aqueous solution as well as in the enzyme although with an opposing effect on the free energy barrier. In the aqueous solution, the transition-state structure involving histamine is better solvated than its methylated analog, leading to a lower barrier for histamine oxidation. In the enzyme, the higher hydrophobicity of N-methylhistamine results in a decreased number of water molecules at the active side, leading to decreased dielectric shielding of the preorganized catalytic electrostatic environment provided by the enzyme. This renders the catalytic environment more efficient for N-methylhistamine, giving rise to a lower barrier relative to histamine. In addition, the transition state involving N-methylhistamine appears to be stabilized by the surrounding nonpolar residues to a larger extent than with unsubstituted histamine, contributing to a lower barrier with the former.     

Characterization of carboxymethylcellulose: Distribution of substituent groups along the chain

A procedure has been developed for characterizing cellulose ethers on the basis of the distribution of substituent groups along the polymer backbone. This method has been applied to carboxy-methylcellulose. The technique uses cellulase, a cellulose-degrading enzyme. Degradation as a function of time is followed by viscosity and reducing sugar measurements. The combination of these data, along with other analytical results, provides information on the number of unsubstituted anhydroglucose residues and the number and average length of blocks of two or more contiguous unsubstituted residues. The results obtained on a series of carboxymethylcellulose samples indicate that the rate of degradation and the number and length of blocks of unsubstituted residues depends not only on the number of substituent groups, but also on other molecular parameters.     

Photomodulated voltammetry investigations on the benzyl radical

Benzyl radicals were generated photochemically directly in an electrochemical cell, using diphenylacetone as a precursor. The half-wave potentials and the plateau current of benzyl radical reduction and respectively oxidation were determined in acetonitrile, propylene carbonate, N,N-dimethylformamide and dimethylsulfoxide. While half-wave potentials and transfer coefficients were independent of chopper frequency and phase setting, the plateau current was markedly influenced by these parameters. The lifetime of the radical was obtained from the dependence of the phase shift of the current on the angular frequency. The influence of precursor concentration, light intensity and nature of the solvent on the radical lifetime was investigated.