两相体系中羟化酶催化-1,2,3,4-四氢喹啉不对称羟基化反应

以菌株Pseudomonas plecoglossicidas ZMU-T02整细胞为生物催化剂,1,2,3,4-四氢喹啉经不对称羟基化反应合成了(R)-4-羟基-1,2,3,4-四氢喹啉,其结构经¹H NMR, ¹³C NMR, HR-MS和HPLC确证。在细胞浓度为30 g cdw·L^-1, pH为9.0,整细胞悬浮液/有机溶剂比例为1 ：1的两相体系中,底物浓度为10 mmol·L^-1时,收率37%, ee值98%。     

1-甲基-5,6,7,8-四氢异喹啉酮-4-甲胺的合成研究

以环己酮为起始原料,经缩合、酰化及酸性水解反应制得2 乙酰基环己酮（1）;在三乙烯二胺催化下,1与氰基乙酰胺环化得四氢异喹啉酮（2）和四氢喹啉酮（3）混合物,在乙醇中回流并趁热过滤进行分离纯化得2和3; 2经催化加氢反应合成1-甲基-5,6,7,8-四氢异喹啉酮-4-甲胺,3步总收率39.8%,其结构经¹H NMR、¹³C NMR、 ¹H-¹⁵N HMBC和MS确证。     

手性1-芳基四氢异喹啉类衍生物的合成新方法

以1,2,3,4-四氢异喹啉为原料,先依次与二碳酸二叔丁酯、亚氯酸钠反应得到N-Boc-1,2,3,4-四氢-1-异喹啉酮,再和芳基格氏试剂反应得到分子内不对称还原胺化反应的底物,最后以ax-Josiphos为手性配体,[Ir(COD)Cl]₂为金属前体,在Ti(OⁱPr)₄和40%HBr溶液组成的催化体系中合成了8个手性1-芳基四氢异喹啉类化合物,其结构经¹H NMR和¹³C NMR表征。该路线提供了一种以廉价1,2,3,4-四氢异喹啉为原料高效合成手性1-芳基四氢异喹啉类衍生物的新方法,为索利那新等药物的合成提供了新路径。      

1,2,3,4-四氢喹啉衍生物合成进展

1,2,3,4-四氢喹啉类化合物是一类重要的含氮杂环化合物,具有众多的生物活性和广泛的用途,因此,四氢喹啉合成新方法的研究受到人们的关注。本文分别从通过氢化还原策略、关环转化反应策略以及通过多分子缩合反应策略等几个方面综述1,2,3,4-四氢喹啉衍生物合成的进展。     

四氢异喹啉衍生物的合成研究

以间甲氧基苯乙胺和氯甲酸乙酯为原料,通过亲核取代、关环、铝锂氢还原、脱甲基以及在N位上Boc保护及脱保护等9步反应得到一系列重要的1,2,3,4-四氢异喹啉及其衍生物.产物的结构经核磁共振氢谱、红外光谱及元素分析确证.与传统四氢异喹啉衍生物的合成工艺相比,该工艺反应条件温和、简便、经济、产率高且对环境友好.     

纳米Ru催化剂催化喹啉加氢反应

制备了高分散性负载型5%Ru/C催化剂,采用X射线衍射、X射线光电子能谱和高分辨透射电镜对催化剂进行了表征.结果表明,所制得的5%Ru/C催化剂分散度高,金属钌的平均粒径小于5nm.在喹啉加氢反应中,催化剂显示出很高的催化活性和生成1,2,3,4-四氢喹啉的选择性,但未检测到十氢喹啉生成.补加新鲜催化剂后,1,2,3,4-四氢喹啉可全部转化为十氢喹啉.对喹啉加氢机理进行了探讨.     

6-羟基-3,4-二氢喹啉-1(2H)-羧酸叔丁基酯的合成研究

以6-羟基喹啉为原料,使用钯碳催化加氢和硼氢化钠还原两种方法合成了6-羟基-1,2,3,4-四氢喹啉化合物,考察反应温度与碱性条件对6-羟基-3,4-二氢喹啉-1(2H)-羧酸叔丁基酯合成收率的影响,10℃反应温度下,以碳酸氢钠作碱是合成的最佳反应条件。     

(S)-N-取代-1,2,3,4-四氢异喹啉-3-甲酰胺催化直接不对称Aldol反应研究

本文研究了以(S) -N-取代-1,2,3,4-四氢异喹啉-3-甲酰胺衍生物的有机小分子催化剂催化不对称Aldol反应,得到高达92%收率和57%的ee值.     

6,7-二甲氧基-1,2,3,4-四氢异喹啉-3-羧酸甲酯的制备——介绍一个大学药物化学综合实验

介绍了我校制药工程专业和药物制剂专业开展的一个综合药物化学实验,该实验以合成PARP1抑制剂的关键中间体6,7-二甲氧基-1,2,3,4-四氢异喹啉-3-羧酸甲酯为目标分子,该化合物是作者课题组目前正在研究的PARP1抑制剂的关键中间体,其合成方法是以L-3,4-二甲氧基苯丙氨酸为原料,甲醇为溶剂,二氯亚砜为脱水剂,室温条件下合成L-3,4-二甲氧基苯丙氨酸甲酯,再以多聚甲醛为原料,二氯甲烷为溶剂,三氟乙酸为催化剂,经Pictet-Spengler反应合成6,7-二甲氧基-1,2,3,4-四氢异喹啉-3-羧酸甲酯,目标化合物的结构使用1H NMR、MS等分析方法进行表征。本实验有益于激发学生独立思考能力和研究意识,训练学生的综合实验操作技能和有机化合物的结构鉴定能力,培养学生掌握药物合成科学研究的基本思路和基本方法。     

2-羟基-5,6,7,8-四氢-5,8-亚甲基喹啉-3-羧酸的合成

5,6,7,8-四氢喹啉及衍生物是医药和农药的重要中间体。2-羟基-5,6,7,8-四氢-5,8-亚甲基喹啉-3-羧酸是合成HIF脯氨酰羟化酶抑制剂的重要中间体,其合成方法目前无文献报道。本文以降冰片烯为起始原料,经水合、氧化、缩合、环合和水解5步反应合成目标产物,总收率43.09%,结构经¹H NMR、 ¹³C NMR和MS确证。该路线具有原料廉价易得、操作简单、后处理方便且收率较高等优点,适合工业化生产。     

二氧化碳和丙烯直接合成甲基丙烯酸的NiPMo/TiO2催化剂的研究

用溶胶-凝胶法以磷钼酸(MPA)的镍盐溶液水解钛酸四丁酯制备了NiPMo/TiO2催化剂.使用ICP、 XRD、 TG-DTA、 IR、 TPD-MS和微反应技术研究了催化剂的化学组成、热稳定性、化学吸附性质和催化反应性能.杂多钼酸盐与TiO2通过O2-在TiO2表面发生了键合.在623 K下,杂多阴离子仍保持原有的Keggin结构.CO2在Lewis酸位Ni(Ⅱ)和Lewis碱位Ni-O-Mo的桥氧协同作用下生成CO2卧式吸附态Ni(Ⅱ)←O-(CO)←(O--Ni).丙烯有多种吸附态在催化剂上吸附.在563 K、 1 MPa和空速1500 h-1的反应条件下,丙烯的摩尔转化率为3.2%,产物MAA选择性为95%.     

Synthesis of 1-benzyloxypyrazin-2(1H)-one derivatives

Different approaches for the synthesis of 1-benzyloxypyrazin-2(1H)-one derivatives from simple amino acids have been investigated. A library of 33 precursors for the preparation of N-hydroxy pyrazinones was obtained in moderate to good yields.     

Toward new camptothecins. Part 6: Synthesis of crucial ketones and their use in Friedländer reaction

In the context of the preparation of camptothecin and luotonin A analogs, the synthesis of some key keto-precursors and their use in Friedländer condensation are described. This paper also focuses on the stability of these keto intermediates and emphasizes the major differences between indolizinones and pyrroloquinazolinones series. Noteworthy is also the report of some original structures isolated as by-products of some experiments.     

CoFe2O4自形成磁性液体场致结构化对磁化的影响

The Langevin paramagnetic theory can’t describe the relation between magnetization of ferrofluids and applied magnetic field. The structuralization of ferrofluids, which is considered the main influence factor of the magnetization, is regarded. The part of magnetization works is deposited when the structure is forming. This action influences the magnetization of ferrofluids directly or indirectly. On the base of the “compressing” model, the Langevin function that usually describes the magnetization of ferrofluid is modified, and a well-fitted curve is obtained. An equation of the relation between the equivalent volume fraction after being “compressed” and the intensity of magnetic field is discovered, which approximately describes the process of magnetization. The relation between the approximate initial susceptibility and the volume fraction can be obtained from modified formula.     

Highly regioselective Buchwald–Hartwig amination at C-2 of 2,4-dichloropyridine enabling a novel approach to 2,4-bisanilinopyridine (BAPyd) libraries

The highly regioselective Buchwald–Hartwig amination at C-2 of the cheap and readily accessible reagent, 2,4-dichloropyridine with a range of anilines and heterocyclic amines is described. This new methodology is robust and provides a facile access to 4-chloro-N-phenylpyridin-2-amines on 0.25 mol scale. These intermediates undergo a further Buchwald–Hartwig amination at higher temperature to enable rapid exploration of the chemical space at C-4 and to provide a library of 2,4-bisaminopyridines.     

KMnO4-mediated oxidative CN bond cleavage of tertiary amines: Synthesis of amides and sulfonamides

KMnO₄-mediated oxidative CN bond cleavage of tertiary amines producing secondary amine was introduced, which was trapped by electrophiles (acyl chloride and sulfonyl chloride) to form amides and sulfonamides. The reaction could take place at mild condition, tolerating a wide range of function groups and affording products in moderate to excellent yields.     

Chemistry of heterocyclic compounds at the A. E. Favorsky Irkutsk Institute of Chemistry, Siberian Branch of the Russian Academy of Sciences, over 50 years (Review)

The review contains a concise historical account and information on the most significant researches undertaken by the staff at the A. E. Favorsky Irkutsk Institute of Chemistry, Siberian Branch of the Russian Academy of Sciences on the Chemistry of Heterocyclic Compounds. Dedicated to Academician of the Russian Academy of Sciences B. A. Trofimov on his 70th jubilee. Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 10, pp. 1443–1502, October, 2008.     

Sulfur-directed metal-free and regiospecific methyl C(sp3)–H imidation of thioanisoles

Regiospecific and direct imidation of the methyl C(sp³)–H bond of thioanisoles is realized under mild and metal-free conditions with N-fluorobis(benzenesulfonyl)imide as an oxidant and nitrogen source. Proposed mechanism suggests that thionium ion intermediates and a Pummerer-type reaction are involved. The imidation has advantages such as high step-economy, excellent functionality tolerance, and regiospecificity, giving structurally diverse imidation products.     

A general and convenient synthesis of 4-(tosylmethyl)semicarbazones and their use in amidoalkylation of hydrogen,heteroatom, and carbon nucleophiles

A general synthesis of previously unknown semicarbazone-based α-amidoalkylating reagents, 4-(tosylmethyl)semicarbazones, has been developed. The synthesis involved three-component condensation of semicarbazones of aliphatic or aromatic aldehydes with the same or other aldehydes and p-toluenesulfinic acid. The scope and limitations of this reaction were investigated. The compounds obtained were demonstrated to be an efficient α-(4-semicarbazono)alkylating agents. They were reacted with H- (sodium borohydride), O- (sodium methylate), S- (sodium phenylthiolate), N- (pyrrolidine, sodium succinimide), P- (trialkyl phosphites), and C-nucleophiles (sodium diethyl malonate) to give the corresponding products of the tosyl group substitution, 4-substituted semicarbazones, including analogues of nitrofurazone. Among the prepared compounds tested in vitro for antibacterial and antifungal activity, three nitrofuryl-containing semicarbazones exhibited high biological activities with minimum inhibitory concentration (MIC) values of 8–32 μg/mL.     

Synthesis of novel chiral bidentate hydroxyalkyl-N-heterocyclic carbene ligands and their application in palladium-catalyzed Mizoroki–Heck couplings and asymmetric addition of diethylzinc to benzaldehyde

A small library of new chiral bidentate hydroxyalkyl-imidazolium salts 1 is conveniently synthesized on multi-gram scale from inexpensive and commercially available chiral pool amino acids. The corresponding carbenes, generated by deprotonation of imidazolium salts 1, in combination with palladium(II) chloride were tested in the Mizoroki–Heck coupling reaction. The most significant results in terms of yields and reactivities were achieved with low catalyst loading. The catalytic activities of these imidazolium salts were also investigated in the asymmetric addition of diethylzinc to benzaldehyde. The use of MgO nanoparticles as an additive in conjunction with these ligands played a crucial role in increasing the efficiency of these reactions.