Regioselectivity in acylation of oligosaccharides catalyzed by the metalloprotease thermolysin

Investigation of the acylation scope of carbohydrates by metalloprotease thermolysin immobilized on Celite as biocatalyst has been carried out. The reactions were performed in DMSO, a good solvent for carbohydrates, where the enzyme has previously shown its activity in transesterifications of sucrose, maltose and maltose-containing oligosaccharides. Surprisingly, no reaction was observed for glucose or the glucose-containing disaccharides, trehalose and lactose. In contrast, laurate monoesters of several sucrose-containing tri- and tetrasaccharides were synthetized through a one step transesterification using vinyl laurate as the acylating agent. Enzyme regioselectivity was accurately determined by HPLC/MS and the structure of the main regioisomers was established by a combination of NMR experiments. The preferred position of acylation in all cases was the 2-OH of the α-d-glucopyranose moiety linked 1→2 to the β-d-fructofuranose unit. These results correlate with the regioselectivity observed in the case of the disaccharide sucrose. A general carbohydrate binding motif for catalysis by thermolysin is proposed.     

Regioselectivity preference of testosterone hydroxylation by cytochrome P450 3A4

Theoretical studies are presented into the experimentally observed regioselectivity difference of testosterone hydroxylation by cytochrome P450 3A4 at the 1β, 2β, 6β, and 15β positions. Such regioselectivity is investigated by density functional theory calculations on a model system. The barrier heights of hydrogen abstraction, which are corrected by zero-point vibrational energies, are computed to be about 10.1, 13.6, 14.4, and 16.2 kcal/mol for the 6β-, 2β-, 15β-, and 1β-positions, respectively. The calculated barriers suggest the regioselectivity preference of 6β ? 2β > 15β > 1β, which is in good agreement with experimental findings.     

室温离子液体催化正己烷异构化反应的研究

由无水三氯化铝与盐酸三乙胺按照不同摩尔比合成了具有不同酸度的室温离子液体,并考察了其酸性以及对正己烷异构化反应的催化性能。结果发现,随着离子液体合成时AlCl3比例的增大,离子液体的酸性增强,且离子液体2AlCl3/Et3NHCl对正己烷异构化显示出优良的催化性能。针对离子液体2AlCl3/Et3NHCl,考察了反应时间、反应温度和催化剂用量（剂油体积比）对正己烷异构化反应的影响。结果表明,反应条件对异构烷烃选择性的影响不大,但是对原料转化率、异构烷烃产率和液体收率有较大的影响。离子液体催化正己烷异构化的最佳反应条件,反应温度为50℃,反应时间为45min,剂油体积比为1∶1。     

Two-state reactivity in alkane hydroxylation by non-heme iron-oxo complexes

Density functional theory is used to explore the mechanisms of alkane hydroxylation for four synthetic non-heme iron(IV)-oxo complexes with three target substrates (Kaizer, J.; Klinker, E. J.; Oh, N. Y.; Rohde; J.-U.; Song, W. J.; Stubna, A.; Kim, J.; Münck, E.; Nam, W.; Que, L., Jr. J. Am. Chem. Soc. 2004, 126, 472-473; Rohde, J.-U.; Que, L., Jr. Angew. Chem. Int. Ed. 2005, 44, 2255-2258.). The iron-oxo reagents possess triplet ground states and low-lying quintet excited states. The set of experimental and theoretical reactivity trends can be understood if the reactions proceed on the two spin states, namely two-state reactivity (TSR); an appropriate new model is presented. The TSR model makes testable predictions: (a) If crossing to the quintet state occurs, the hydroxylation will be effectively concerted; however, if the process transpires only on the triplet surface, stepwise hydroxylation will occur, and side products derived from radical intermediates would be observed (e.g., loss of stereochemistry). (b) In cases of crossing en route to the quintet transition state, one expects kinetic isotope effects (KIEs) typical of tunneling. (c) In situations where the two surfaces contribute to the rate, one expects intermediate KIEs and radical scrambling patterns that reflect the two processes. (d) Solvent effects on these reactions are expected to be very large.     

Regioselectivity of olefin oxidation by iodosobenzene catalyzed by metalloporphyrins : control by the catalyst

The regioselectivity of the oxidation of three monosubstituted olefins, 6-phenoxyhex-1-ene, hex-1-ene and styrene, by iodosobenzene in the presence of various Fe-, Mn- or Cr-tetraaryl-porphyrins, was studied. It was found that, besides epoxides, known products from such systems, allylic alcohols and aldehydes were formed, the latter not being derived from the corresponding epoxides. The relative importance of these reactions greatly depends upon both the metal and porphyrin constituents of the catalyst. More particularly, the competition between epoxidation and allylic hydroxylation can be efficiently controlled by non-bonded interactions between the olefin and porphyrin substituents. No hydroxylation of the aromatic rings and no oxidative dealkylation of the ether function was detected.     

铁卟啉催化二乙基亚硝胺羟基化的反应机理

采用密度泛函理论(DFT)对P450酶活性中心铁卟啉Cpd I催化二乙基亚硝胺(NDEA)代谢活化的反应机理进行了研究.结果表明,Cpd I催化NDEA羟基化的过程包含氢抽提反应和回弹反应2个步骤.其中,氢抽提反应为控速步骤,氢自由基从NDEA转移到铁卟啉的Fe O上,是典型的氢原子传递(HAT)过程;紧接着铁卟啉上的羟基经历无能垒的反应过程回弹到NDEA自由基上,形成羟基化代谢产物.NDEA羟基化过程中高自旋态(HS)和低自旋态(LS)均参与反应,整个羟基化过程呈现明显的双态反应性(TSR).研究比较了NDEA分子侧链上Cα—H和Cβ—H羟基化反应的差异,得到Cα—H和Cβ—H羟基化所需跨越的能垒分别为57.7/57.7 k J/mol(LS/HS)和76.4/74.3 k J/mol(LS/HS),表明Cα—H比Cβ—H更易于在P450作用下发生羟基化;此外,Cβ—H羟基化所需克服的能垒并未过高,使得Cβ—H羟基化在生理条件下完全也有可能发生.本研究为深入揭示亚硝胺经代谢活化导致癌症的作用机制提供了可靠的理论依据.     

Regioselectivity of aliphatic versus aromatic hydroxylation by a nonheme iron(II)-superoxo complex

Many enzymes in nature utilize molecular oxygen on an iron center for the catalysis of substrate hydroxylation. In recent years, great progress has been made in understanding the function and properties of iron(IV)-oxo complexes; however, little is known about the reactivity of iron(II)-superoxo intermediates in substrate activation. It has been proposed recently that iron(II)-superoxo intermediates take part as hydrogen abstraction species in the catalytic cycles of nonheme iron enzymes. To gain insight into oxygen atom transfer reactions by the nonheme iron(II)-superoxo species, we performed a density functional theory study on the aliphatic and aromatic hydroxylation reactions using a biomimetic model complex. The calculations show that nonheme iron(II)-superoxo complexes can be considered as effective oxidants in hydrogen atom abstraction reactions, for which we find a low barrier of 14.7 kcal mol(-1) on the sextet spin state surface. On the other hand, electrophilic reactions, such as aromatic hydroxylation, encounter much higher (>20 kcal mol(-1)) barrier heights and therefore are unlikely to proceed. A thermodynamic analysis puts our barrier heights into a larger context of previous studies using nonheme iron(IV)-oxo oxidants and predicts the activity of enzymatic iron(II)-superoxo intermediates.     

Regioselectivity in reactions of alkynylmetal complexes with pyrimidinones

Regioselectivity is observed in $\text{1}\text{1}$-adduct formation between phenylethynyltriisopropoxytitanium and 2(1/H)-pyrimidinones; the new carbon-carbon bond is formed at C(4). In contrast the 3,4- and 3,6-dihydro products are formed together from the corresponding magnesium and lithium reagents, but from the magnesium compound the major product is the 3,6-dihydro isomer. Ethynylmagnesium bromide gives equimolar amounts of the 3,4- and 3,6-dihydro isomers. Dehydrogenation of the products gives the alkynylated aromatic heterocycles.     

引发剂对离子液体催化正己烷异构化反应的影响

由无水三氯化铝与盐酸三乙胺按照摩尔比2∶1合成了离子液体2AlCl3/Et3NHCl,并考察了其催化正己烷异构化的反应性能。发现离子液体2AlCl3/Et3NHCl可用于催化正己烷的异构化反应,但所需的反应时间较长。考察了引发剂正丁醇、异丁烯、异丁烷和异戊烷对离子液体催化正己烷异构化反应的影响。发现异戊烷作为引发剂时,正己烷的转化率为84.54%,液体收率为80.08%,异构烷烃的选择性为94.74%,达到了较好的反应效果。引发剂异戊烷的用量对异构化反应有着较大的影响,较优的引发剂用量为30%。添加异戊烷引发剂能明显提高离子液体催化正己烷异构化的反应速度,达到相似反应程度的反应时间可由6h缩短为45min。     

V@CN催化的芳烃的氧气羟基化反应

制备了V@CN催化剂,并用于氧气条件下芳烃的直接羟基化反应。结果表明,在V@CN催化剂作用下,带有不同吸电子基团(CN, NO2, COOH, CF3和COCH3)的芳烃均可被O2氧化得到相应的酚,产率中等。含有卤素(F, Cl和Br)的芳烃也可在该催化体系作用下转化为相应的酚。     

铁卟啉化合物的合成及其催化环己烷羟基化反应的研究

合成了15种卟啉环上具有不同取代基和纵轴上具有不同配位基的TRPPFe^ⅢCl和TPPFe^ⅢX, 从反应速率、反应产率和产物选择性等方面考察了卟啉环上取代基R和纵轴配位基X对这些铁卟啉在温和条件下催化环己烷羟基化反应催化性能的影响,还研究了反应溶剂、反应温度以及有机碱等环境因素对铁卟啉催化性能的影响,获得了一些新的结果和规律。     

Osmium tetroxide catalyzed hydroxylation of hindered olefins

Osmium tetroxide catalyzed hydroxylation of sterically hindered olefins proceeds efficiently with trimethylamine N-oxide as oxidizing agent in the presence of pyridine.     

金属卟啉催化环己烷羟基化反应中环己酮的形成机理研究

单金属卟啉和双金属卟啉催化下PhIO常温氧化环己烷的羟基化反应中金属卟啉结构和反应溶剂、反应温度、反应时间等环境因素对产物酮含量及酮形成反应动力学的影响进行了系统研究, 并与金属卟啉催化下PhIO氧化环己醇的反应进行了对比, 提出了金属卟啉催化下环己烷羟基化反应中产物酮的形成机理。     

金属卟啉催化环己烷羟基化反应中环己酮的形成机理研究

单金属卟啉和双金属卟啉催化下PhIO常温氧化环己烷的羟基化反应中金属卟啉结构和反应溶剂、反应温度、反应时间等环境因素对产物酮含量及酮形成反应动力学的影响进行了系统研究, 并与金属卟啉催化下PhIO氧化环己醇的反应进行了对比, 提出了金属卟啉催化下环己烷羟基化反应中产物酮的形成机理。     

海藻酸铜负载CuTIPP催化羟化苯酚的研究

将四(对异丙基苯基)铜卟啉(CuTIPP)分散于海藻酸钠胶珠中,通过与铜离子水溶液反应制得海藻酸铜—CuTIPP胶珠。以双氧水为氧化剂,风干的胶珠为催化剂,对苯酚的催化羟化反应进行了探究。实验结果表明:负载CuTIPP的海藻酸铜催化剂催化活性要高于海藻酸铜催化剂,苯二酚的产率相对于海藻酸铜提高了9%,苯酚转化率达到了40.2%,苯二酚邻、对比接近4∶5。     

Base-free Mizoroki-Heck reaction catalyzed by rhodium complexes

A base-free rhodium-catalyzed Mizoroki-Heck (M-H) reaction using potassium aryltrifluoroborates as the arylating agent of alkenes and acetone as a green "oxidant" is described. Thanks to the ready availability of organoboranes, this reaction should constitute an interesting alternative to conventional M-H reactions using aryl halides.     

Ester hydrogenation catalyzed by Ru-CNN pincer complexes

We report new Ru-CNN pincer catalysts for ester hydrogenation under mild conditions.