固定化细胞酶法拆分N-乙酰-D,L-3-甲氧基丙氨酸

利用氨基酰化酶固定化细胞酶法拆分了N-乙酰-D,L-3-甲氧基丙氨酸. 考察了温度、pH值、底物浓度、金属离子和拆分时间对酶促反应的影响. 确定了氨基酰化酶固定化细胞手性拆分N-乙酰-D,L-3-甲氧基丙氨酸的最佳工艺条件为pH=7.0, 反应温度50 ℃及底物浓度500 mmol/L. 10^-4 mol/L的Co²⁺和Mg²⁺对氨基酰化酶有显著激活作用, Cu²⁺和Zn²⁺对酶促反应有明显抑制作用. 在最佳条件下, 氨基酰化酶固定化细胞对N-乙酰-L-3-甲氧基丙氨酸的摩尔转化率达96%.     

双层固定化酵母催化还原4-氯-乙酰乙酸乙酯的研究

以海藻酸钠为内层载体,利用机械强度良好的聚乙烯醇(PVA)改性海藻酸钠混合物作为外层载体,双层固定化高活性酵母,得到固载的生物催化剂,用于由磷酸缓冲溶液和环己烷组成的双相体系,对4-氯-乙酰乙酸乙酯(COBE,ethyl 4-cloro-3-oxobutyrate)进行不对称催化加氢合成(S)-4-氯-3-羟基丁酸乙酯[(S)-CHBE],ethyl[(S)-4-chloro-3-hydro butanoate].在最适条件下,双层固定化酵母的不对称催化还原反应优于游离细胞和单层固定化细胞.在底物COBE的最佳浓度和进料速率分别为170mmol/L,125mL/h的连续操作条件下,最高(S)-CHBE转化率为94.2%,最高对映体过量值为98%.与游离细胞催化COBE相比,反应转化率提高3%,最佳底物浓度比游离细胞增加1倍;与单层固定化细胞催化还原相比,对映体过量值提高8%.连续性实验表明,双层固定化酵母细胞在连续使用5d,其转化率和对映选择性没有明显下降.     

微水相中改性Ultrastable-Y分子筛固定化脂肪酶拆分(R,S)-2-辛醇

采用改性Ultrastable-Y分子筛固定化P. expansum PED-03脂肪酶(PEL), 利用固定化PEL在微水相中对(R,S)-2-辛醇进行拆分. 结果表明, 改性Ultrastable-Y分子筛固定化PEL所催化的拆分反应的转化率(c)和对映体过量值(e.e.)以及对映体选择性(E)均得到大幅度提高. 介质类型和体系含水量对酶促拆分反应有较大的影响. 在以正己烷为溶剂, 含水量为0.8%的体系中, 于50 ℃反应24 h的转化率(c)可达到理论值的97.68%, 对映体过量值(e.e.)可达到98.75%. 改性Ultrastable-Y分子筛固定化PEL催化效率高、立体选择性强, 且催化性能稳定, 在(R,S)-2-辛醇的酶法拆分方面具有良好的应用前景.     

用芹菜茎催化对映选择性还原芳香酮

研究了用芹菜茎薄片在温和与环境友好的条件下催化芳香酮的对映选择性还原反应, 制备得到具有光学活性的(S)-1-芳基醇, 产物的对映选择性符合Prelog规则. 考察了pH值、反应时间、反应温度、底物浓度等因素对底物芳香酮的转化率和产物(S)-1-芳基醇的对映体过量值的影响, 并优化了这些反应条件. 文中还研究了底物的构效关系, 发现羰基两边取代基的空间效应和电子效应明显影响底物的转化率和产物的对映体过量值. 在合适的条件下底物苯乙酮的转化率高达100%, 产物(S)-1-苯基乙醇的对映体过量值大于99.0%. 苯丙酮、对甲基苯乙酮和对氯苯乙酮等其它芳香酮的转化率达到中等程度, 但所得(S)-1-芳基醇的最大对映体过量值均大于99.0%.     

用芹菜茎生物催化对映选择性还原芳香酮

研究了用芹菜茎薄片在温和与环境友好的条件下催化芳香酮的对映选择性还原反应.制备得到具有光学活性的(S)-1-芳基醇,产物的对映选择性符合Prelog规则.考察了pH值、反应时间、反应温度、底物浓度等因素对底物芳香酮的转化率和产物(S)-1-芳基醇的对映体过量值的影响,并优化了这些反应条件.文中还研究了底物的构效关系,发现羰基两边取代基的空间效应和电子效应明显影响底物的转化率和产物的对映体过量值.在合适的条件下底物苯乙酮的转化率高达100%,产物(S)-1-苯基乙醇的对映体过量值大于99.0%.苯丙酮、对甲基苯乙酮和对氯苯乙酮等其它芳香酮的转化率达到中等程度,但所得(S)-1.芳基醇的最大对映体过量值均大于99.0%.     

酶法拆分D,L-苯丙氨酸制备D-苯丙氨酸

在固定化青霉素酰化酶(IPA-750)存在下,通过N-苯乙酰-D,L-苯丙氨酸(2)的选择性水解完成了酶法拆分D,L-苯丙氨酸(1)制备D-苯丙氨酸(5)的过程。选择性水解的较适宜反应条件为:22.83g,m(2)∶m(IPA-750)=6∶1,pH7.0,于30℃反应5h,产物为N-苯乙酰-D-苯丙氨酸(4)和L-苯丙氨酸(3,收率63%,光学纯度99%)。4用6mol·L-1盐酸于120℃水解反应8h,经脱盐处理得5,收率67%,光学纯度91%。3在含醋酸酐的醋酸溶液中进行消旋化处理,得到100%消旋的1可继续进行下一轮酶法拆分。     

固定化嗜热酯酶催化拆分(R,S)-2-甲基-1-丁醇

利用帆布固定化嗜热酯酶APE1547(3)在非水介质中催化转酯化反应进行酶促拆分(R,S)-2-甲基-1-丁醇制备(S)-2-甲基-1-丁醇(4).初步探讨了溶剂、酰基供体、温度及底物配比对3的催化活力(EA3)′与4对映选择性比率(E4)的影响.在最佳拆分条件下,EA3 =0.53 μmol·min-1·mg-1,E4=15.4.3套用8次后仍然保持较高的催化活性.     

水/有机溶剂双相中郁李醇腈酶催化含硅(R)-酮氰醇对映选择性合成

 研究了水/有机溶剂双相中来源于郁李仁的(R)-醇腈酶催化2-三甲基硅-2-乙酮与2-甲基-2-羟基丙腈对映选择性合成(R)-2-三甲基硅-2-羟基丙腈,初步探讨了反应时间、酶粉颗粒大小、底物浓度、底物配比和酶添加量对转氰反应的影响. 结果表明,适宜的反应条件为: 反应时间96 h左右, 酶粉颗粒大小0.3～0.45 mm, 底物2-三甲基硅-2-乙酮浓度14 mmol/L, 底物2-甲基-2-羟基丙腈与2-三甲基硅-2-乙酮摩尔比2:1, 单位体积反应介质中的酶添加量43.5 g/L左右. 在该优化反应条件下,反应平衡转化率和产物的光学纯度(ee值)均可高达99%. 对比研究发现,郁李醇腈酶催化2-三甲基硅-2-乙酮反应在酶促反应初速率、底物转化率和产物光学纯度等方面均显著优于其碳结构类似物3,3-二甲基-2-丁酮.     

相转移催化法和手性催化加氢法立体选择性地合成Fmoc保护的(S)-3,5-二溴苯丙氨酸

通过两种不对称催化方法合成了(S)-3,5-二溴苯丙氨酸.一种方法是以二苯亚胺甘氨酸叔丁酯和3,5-二溴苄基溴为底物,在O-烯丙基-N-9-蒽甲基溴化辛可宁定催化下,经不对称烷基化反应得到了(S)-3,5-二溴苯丙氨酸的衍生物,ee值达到94.9%,重点优化了不对称相转移催化烷基化反应的条件,得到了最优反应条件.另一种方法是以2-乙酰胺基-3-(3,5-二溴苯基)丙烯酸为底物,在双(1,5-环辛二烯)-三氟甲磺酸铑(I)和(R)-N-二苯基膦-N-甲基-(S)-2-(二苯基膦)二茂铁基乙胺催化下加氢得到乙酰基保护的(S)-3,5-二溴苯丙氨酸,再进行水解反应,最终得到(S)-3,5-二溴苯丙氨酸.经Fmoc的保护,得到Fmoc保护的(S)-3,5-二溴苯丙氨酸,ee值达到94.7%.所述两种方法中,第一种方法产率较高,对映选择性也较高,适合应用于其他手性二卤代苯丙氨酸的合成.     

酵母细胞催化芳香酮的不对称还原反应

 研究了酵母细胞催化芳香酮的不对称还原反应,采用正交试验综合考察了反应温度、反应时间、底物浓度和酵母浓度等因素对底物苯乙酮转化率和产物(S)-1-苯基乙醇对映选择性的影响. 结果表明,影响苯乙酮转化率的因素依次为底物浓度、反应时间、反应温度和酵母浓度,影响(S)-1-苯基乙醇对映选择性的因素依次为反应温度、底物浓度、酵母浓度和反应时间. 同时考察了芳香酮结构对产物对映选择性的影响,发现对映选择性的变化规律符合Prelog规则,与羰基相连的两个基团体积差异越大,对映选择性越好,最高的对映体过量值达到了96.4%.     

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%.     

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.     

α-Amino acid derived enaminones and their application in the synthesis of N-protected methyl 5-substituted-4-hydroxypyrrole-3-carboxylates and other heterocycles

A new and simple synthesis of novel N-protected methyl 5-substituted-4-hydroxypyrrole-3-carboxylates, which exist in equilibrium with their 4-oxo tautomers, has been developed in two steps starting from N-protected α-amino acids. The key intermediates are enaminones, which can also be isolated, characterized, and used for the construction of other functionalized heterocycles, before they spontaneously decompose to pyrrole products. 4-Hydroxypyrroles are prone to partial aerial oxidation but can be efficiently alkylated or reduced to stable polysubstituted pyrrolidine derivatives.     

Specific intramolecular aromatic CH insertion of diazosulfonamides

The chemoselectivity in the intramolecular CH insertion of various diazosulfonamides has been experimentally studied. The results reveal that the aliphatic 1,4-, 1,5-, or 1,6-C(sp³)?H insertions of diazosulfonamides are not accessible, while the aromatic 1,5-C(sp²)?H insertion can be realized specifically by adjusting the diazo-adjacent group. In addition, the general chemoselectivities in the intramolecular CH insertions of diazosulfonyl compounds are summarized. Generally, diazosulfones undergo both aromatic 1,5-C(sp²)?H and aliphatic 1,5- and 1,6-C(sp³)?H insertions, while diazosulfonates undergo aliphatic 1,5- and 1,6-C(sp³)?H insertions. However, diazosulfonamides only undergo aromatic 1,5-C(sp²)?H insertion.     

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.     

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.     

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.     

N-Heterocyclic carbene-palladacyclic complexes: synthesis,characterization and their applications in the C-N coupling and α-arylation of ketones using aryl chlorides

N-Heterocyclic carbene-palladacyclic complexes 3 were successfully achieved in a one-pot procedure under mild conditions. The structure of 3a was unambiguously confirmed by X-ray single crystal diffraction and it was an active catalyst in the Buchwald-Hartwig amination and α-arylation of ketones even at very low catalyst loadings (0.01?mol%).     

Iodine-mediated oxidative Pictet-Spengler reaction using terminal alkyne as the 2-oxoaldehyde surrogate for the synthesis of 1-aroyl-β-carbolines and fused-nitrogen heterocycles

An efficient iodine-mediated oxidative Pictet-Spengler reaction in dimethyl sulphoxide (DMSO) using terminal alkynes as the 2-oxoaldehyde surrogate for the synthesis of aryl (9H-pyrido[3,4-b]indol-1-yl)methanones is described. The scope of the protocol includes the total synthesis of Fascaplysin, Eudistomins Y₁ and Y₂. The methodology is extended for preparing pyrrolo[1,2-a]-quinoxaline and indolo[1,5-a]quinoxaline derivatives. The utility of 1-aroyl-β-carbolines was demonstrated by performing palladium-catalyzed β-carboline directed ortho-C(sp2)-H functionalization of the phenyl ring with thiomethyl (SMe) group using DMSO as source and for accessing 4-aryl-canthin-6-ones.