Direct Reductive Cyanation of A 2-Pyrrolidinone Chiral Building Block Bearing An Unprotected Hydroxyl Group: A Stereoselective Synthesis of N-Methyl-2-epi-bulgecinine

报道手性合成砌块(4S,5R)-N-芐氧基-5-羟甲基-2-吡咯烷酮(3a)的直接还原氰基化及产物的立体化学与转化研究.含未保护羟基的内酰胺用L; iAlH_4/KCN体系直接还原氰基化,生成比例为69:; 31的2,5-反式/顺式非对映立体异构体.与文献类似结果对比显示,氰基负离子对5-羟甲基-△-1-吡咯啉鎗中间体的加成主要受立体电子效应和C(5; )位取代基(羟甲基)与进攻试剂间烯丙型1,3-位阻控制.该混合物在碱性条件下水解,生成比例为10:; 90的2,5-反式/2,5-顺式-bulgecinine衍生物.这一结果表明氰基水解反应伴随着在C(2)位发生了有合成价值的串联差向异构化.由此; 建立了立体选择性地合成2,5-顺式(-)-N-甲基-2-别-bulgecinine的简便方法.The direct reductive cyanation of N-benzyl-4-benzyloxy-5-hydroxymethyl-2-pyrrolidinone (3a), a lactam bearing a free hydroxyl group, has been achieved with the LiAlH4/KCN combination. The reaction afforded 2,5-trans-2-cyano-5hydroxylmethyl-4-benzyloxy-pyrrolidine (5a) and its cis-diastereomer 5b in a ratio of 69: 31 with a combined yield of 63%. The observed 2,5-trans-stereoselectivity is suggested to be resulted from both stereoelectronic effect and allylic 1,3-strain between the hydroxymethyl group at C(5) and the incoming cyanide anion on the presumed Delta-1 pyrrolinium ion intermediate. The subsequent hydrolysis of the cyano group of the diastereomeric mixture 5a/5b (trans: cis=69: 31) under basic conditions afforded the corresponding 5-hydroxymethyl-4-benzyloxyproline with 2,5-cis-diastereomer as the major diastereomer (trans: cis= 10: 90). This result implies that a synthetically useful epimerization at C(2) has occurred concomitantly. This unexpected result afforded a concise and highly stereoselective synthesis of 2,5-cis-(-)-N-methyl-2-epi-bulgecinine.National Natural Science Foundation of China [21332007]; Program for; Changjiang Scholars and Innovative Research Team in University of; Ministry of Educatio

光动力学方法（PDT）治疗多形性腺瘤恶变一例报告

多形性腺瘤恶变采用PdT治疗国内尚未见报道。我科1988年治愈一例，存活至今已7年未复发。患者张xx，女，30岁，1985年右上唇颊沟长一肿物，在某地区医院手术切除三次复发。1987年7月21日我科收住院。入院检查：全身情况营养较差，消瘦、肝功gPT..

Theoretical Study of Substituent Effects on Bond Dissociation Enthalpies in Lignite Model Compounds

为了探究褐煤热解过程中氧桥键C—O均裂这一重要反应,选取α-O-4和β-O-4类结构单元作为褐煤模型化合物,运用不同密度泛函计算了部分模型化合物中C—O的离解焓,并以CbS-Qb3作为理论基准值进行比较,最后选取M05-2X进行离解焓计算.结果显示,对于选定的α-O-4和β-O-4类模型化合物,其平均离解焓分别为51.0 kCAl/MOl和66.1 kCAl/MOl.周围取代环境能显著影响C—O离解焓,芳环上存在给电子基团(OH,OCH3和CH3)能降低C—O离解焓,而吸电子基团COOH则能增加其离解焓.然后深层次分析了取代基效应对C—O离解焓的影响.此外,分子内氢键的形成对离解焓也有很大的影响.C—O的离解焓与其键长没有特定的相关性,不能简单的通过C—O键长来预测其离解焓.Lignite is an abundant natural resource that is a potential source of clean fuel and value-added chemicals.The mechanisms by which thermal and catalytic treatments deconstruct lignite remain elusive,which is where quantum mechani-cal calculations can offer fundamental insights.In order to investigate the cleavage of C—O bridge bond,which is the critical step in the thermal decomposition of lignite,the α-O-4 and β-O-4 types of structural units are selected as lignite model com-pounds to calculate the C—O bond dissociation enthalpies using several kinds of density functional theory methods(B3PW91,B3P86,PBE1PBE,BMK,M06-2X and M05-2X) at 6-31+G(d,p) level.By the comparison between the results and the theoretical benchmark values provided by CBS-QB3 method,M05-2X functional was applied for the calculations on C—O bond dissociation enthalpies.The present results indicate that the C—O average bond dissociation enthalpies are 51.0 kcal/mol and 66.1 kcal/mol for the α-O-4 and β-O-4 types of model compounds,respectively.Local substituents have a great withdrawing groups such as carboxyl group.Then the substituent effects are deeply analyzed on the basis of the ground-state effect on the C—O bond dissociation enthalpies,the C—O bond dissociation enthalpies will decrease when the adjacent arene rings are substituted by electron donating groups(OH,OCH3 and CH3),while the results are opposite for the electron effect and radical effect.An electron donating group can stabilize the phenoxy radicals(radical effect),however,an electron withdrawing group has the opposite effect.In most cases,the radical effect is more important than the ground-state effect.Furthermore,there is a negligible correlation between the C—O bond distances and strengths,and the C—O bond dissocia-tion enthalpies cannot be predicted so easily.Interestingly,the C—O bond dissociation enthalpies can be significantly influ-enced by the intramolecular hydrogen bond,if the intramolecular hydrogen bond still exists after the cleavage of the C—O bond,the bond dissociation enthalpies will be lower.国家重点基础研究发展计划(No.2012CB214901); 国家自然科学基金(No.51274197)资助~

内镜下萨氏扩张器扩张联合局部注射曲安奈德治疗食管良性吻合口狭窄的疗效及安全性研究

目的:探讨食管良性吻合口狭窄经内镜下萨氏扩张器扩张联合局部注射曲安奈德治疗的临床疗效及安全性。方法:选取79例食管良性吻合口狭窄患者作为研究对象,根据数字表法将其随机分为对照组(n=38)和研究组(n=41),对照组给予内镜下萨氏扩张器扩张治疗,研究组在对照组基础上联合局部注射曲安奈德治疗,比较两组患者临床疗效、术后恢复情况以及安全性。结果:研究组治疗后总有效率为85.37%(35/41),高于对照组患者的65.79%(25/38)(x~2=4.138,P=0.002)。研究组持续症状缓解时间、再次进行内镜下扩张治疗的间隔时间均长于对照组(t=21.573、27.209,P=0.000、0.000),两组患者治疗前Stooler评分比较差异无统计学意义(t=0.266,P=0.791),两组患者治疗后Stooler评分均降低(t=16.606、25.962,P=0.000、0.000),且研究组低于对照组(t=7.407,P=0.000)。研究组术后并发症总发生率为19.51%(8/41),低于对照组患者的42.11%(16/38)(x~2=4.760,P=0.009)。结论:食管良性吻合口狭窄经内镜下萨氏扩张器扩张联合局部注射曲安奈德治疗后,可获得较好的疗效,患者临床症状得到改善,同时还可减少并发症发生率,临床应用价值较高。福建省科技计划引导性项目(2016D00210

A nanoparticulate polyacetylene-supported Pd(Ⅱ) catalyst combining the advantages of homogeneous and heterogeneous catalysts

负载型的金属催化剂虽然分离方便,但在反应活性、选择性以及催化剂的结构表征方面均明显不如相应的均相催化剂.将均相催化剂通过不同的化学键固载于高比表面积载体是实现均相催化剂多相化的重要途径,这样可使催化剂兼具均相和多相催化剂的优势.然而要将均相催化剂锚定于特定载体上,通常涉及较为复杂的合成反应,对载体也有严格的要求.因而该法仅仅适用于实验室研究,难以实现规模生产.因此,提供一种简便有效地制备兼具均相和多相催化剂优势的催化剂合成方法非常必要.本文报道一种简便的制备聚乙炔纳米颗粒负载Pd(Ⅱ)催化剂(nP-Pd(Ⅱ))的方法,所制催化剂在水相中的SuzukI-MIyAurA偶联反应中表现出极高的活性,同时具有便于分离、容易放大制备的特点.在室温下,将乙炔气通入PdC l2-4的水溶液中迅速变得浑浊,静置后容器底部有棕色沉淀,同时溶液变为无色透明.固体产物使用水、乙醇等溶剂进行洗涤;干燥之后收集既得聚乙炔纳米颗粒负载的Pd(Ⅱ)催化剂nP-Pd(Ⅱ).使用透射电子显微镜、红外(Ir)及拉曼吸收光谱、X射线衍射(Xrd)、X射线光电子能谱(XPS)以及X射线吸收光谱(EXAfS)等手段对nP-Pd(Ⅱ)进行了详细表征.结果显示,在nP-Pd(Ⅱ)中Pd并非以Pd纳米颗粒形式存在;Xrd中没有未Pd纳米晶的特征衍射峰.Ir等表征证明乙炔在Pd的催化作用下发生聚合作用,生成了聚乙炔.EXAfS结果表明,Pd分别和氯原子以及C=C双键进行配位;同时,没有观察到Pd–Pd键的生成,进一步证明了Pd未被还原为Pd纳米颗粒.XPS也印证了Pd(Ⅱ)的价态.形貌上,nP-Pd(Ⅱ)为直径2–3nM的颗粒,其中的Pd原子均匀分散于聚乙炔纳米颗粒上,使其在反应过程中能够充分地与底物接触,从而在SuzukI-MIyAurA偶联反应中表现出极高的活性.更重要的是,由于“憎水效应“,nP-Pd(Ⅱ)在溶液中以微米级的聚集体形式存在,因而反应后通过离心或者静置从反应体系中分离出来.因此,在nP-Pd(Ⅱ)催化剂中,每个Pd原子都是潜在的活性中心,这与典型的均相催化剂相似;同时,其独特的形貌使其具备了多相催化剂便于分离的特点.因此,nP-Pd(Ⅱ)是一种兼具均相和多相催化剂优点的催化剂且其催化剂的制备方法极为简便.乙炔是常用的工业气体,溶剂采用水,制备在室温下即可完成,我们也成功地制备出克级规模的高活性、稳定性的nP-Pd(Ⅱ)催化剂.A novel nanoparticulate polyacetylene-supported Pd(Ⅱ) catalyst(NP-Pd(Ⅱ)) for use in the aqueous Suzuki-Miyaura cross coupling reaction was successfully synthesized by simply treating an aqueous solution of PdC l42- with acetylene under ambient conditions.Electron microscopy, Fourier transform infrared spectroscopy, Raman spectroscopy, X-ray diffraction, X-ray photoelectron spectroscopy and X-ray absorption spectroscopy were employed to characterize the NP-Pd(Ⅱ) structure in detail.These analyses demonstrated that the Pd atoms in the NP-Pd(Ⅱ) were present as Pd(Ⅱ) and were coordinated with both the Cl atoms and the C=C bonds of the polyacetylene.Both the homogeneous distribution of the Pd(Ⅱ) along the polyacetylene backbone and the aggregation of the NP-Pd(Ⅱ) in solution work in conjunction to make this material an ideal catalyst, combining the advantages of both homogeneous and heterogeneous catalysts.supportedbyMinistryofScienceandTechnologyofChina(2011CB932403;2015CB932303); theNationalNaturalScienceFoundationofChina(221420102001;21131005;21390390;21333008)~

The application and research of the aircraft flexible fixture

主要研究气动、液压与电传技术在航空制造业中装配工艺中的应用。对研制出数控机床气动柔性夹紧系统,及其在飞机上零件加工上的应用进行了详细论述,包括柔性系统的机构组成、工作原理及PlC控制系统。该技术的突破为我国飞机数字化加工装配提供了参考价值,并将促进航空制造业的跨越式发展。The application of the pneumatic,hydraulic and power transmission for assembly process and equipment in aviation manufacturing industry is study.A novel type of CNC Aircraft Flexible Fixture machine system has been made out,and applied in manufacturing the aircraft parts.The system is including in architecture of the composition,working theory,PLC control system.It has a great signification of the manufacturing technology for aircraft digital processing,manufacturing and assembling,and promoting the developing of aircraft manufacturing

多粘菌素菌种选育和发酵技术研究进展

由于具有一定肾毒性和神经毒性,多粘菌素在过去相当长一段时间内一直是二线药物。耐药细菌的出现和相应疗药的有限使多粘菌素重新进入临床实践中,多粘菌素在治疗革兰阴性菌,特别是铜绿假单胞菌、鲍曼不动杆菌和肺炎克雷伯杆菌导致的感染方面疗效确切,引起人们的极大重视。多粘菌素的发酵生产是其药理研究和临床应用的基础。然而,我国多粘菌素的发酵产量远低于发达国家,以致多粘菌素严重依赖进口且价格昂贵。本研究从多粘菌素菌种选育、培养基优化、培养条件优化和培养过程优化与控制等四个方面对近年来相关研究进行了梳理和总结,指出上述研究中用到的方法和策略,期望为多粘菌素工业生产和应用提供参考

多粘菌素菌种选育和发酵技术研究进展

由于具有一定肾毒性和神经毒性,多粘菌素在过去相当长一段时间内一直是二线药物。耐药细菌的出现和相应疗药的有限使多粘菌素重新进入临床实践中,多粘菌素在治疗革兰阴性菌,特别是铜绿假单胞菌、鲍曼不动杆菌和肺炎克雷伯杆菌导致的感染方面疗效确切,引起人们的极大重视。多粘菌素的发酵生产是其药理研究和临床应用的基础。然而,我国多粘菌素的发酵产量远低于发达国家,以致多粘菌素严重依赖进口且价格昂贵。本研究从多粘菌素菌种选育、培养基优化、培养条件优化和培养过程优化与控制等四个方面对近年来相关研究进行了梳理和总结,指出上述研究中用到的方法和策略,期望为多粘菌素工业生产和应用提供参考

多粘菌素菌种选育和发酵技术研究进展

由于具有一定肾毒性和神经毒性,多粘菌素在过去相当长一段时间内一直是二线药物。耐药细菌的出现和相应疗药的有限使多粘菌素重新进入临床实践中,多粘菌素在治疗革兰阴性菌,特别是铜绿假单胞菌、鲍曼不动杆菌和肺炎克雷伯杆菌导致的感染方面疗效确切,引起人们的极大重视。多粘菌素的发酵生产是其药理研究和临床应用的基础。然而,我国多粘菌素的发酵产量远低于发达国家,以致多粘菌素严重依赖进口且价格昂贵。本研究从多粘菌素菌种选育、培养基优化、培养条件优化和培养过程优化与控制等四个方面对近年来相关研究进行了梳理和总结,指出上述研究中用到的方法和策略,期望为多粘菌素工业生产和应用提供参考。</p