苯胺类化合物的电化学氧化及随后化学反应

利用循环伏安法研究了二取代对苯二胺(1),四取代对苯二胺(2)和二取代氨基酚(3)三类化合物以及它们的衍生物的电化学行为及其氧化产物的随后不可逆脱氨反应。 1类化合物在任何pH下的电化学氧化均为一步双电子转移反应,2类化合物为二步单电子转移反应;3类化合物在酸性和中性范围为一步双电子氧化在碱性溶液中为二步单电子转移反应。文中定量求算了不可逆随后化学反应的表观水解速率常数k_f,并进行了讨论。     

Ab initio and DFT modeling of stereoselective deamination of aziridines by nitrosyl chloride

The stereochemical course of the deamination of cis‐2,3‐dimethylaziridine by nitrosyl chloride was investigated at the QCISD/6‐31G(d) level. Calculations reveal that the reaction takes place in two steps. In the first step, the reactants form a pre‐reactive complex, followed by a spiro‐type bicyclic transition state, which on dissociative cycloelimination gives the N‐nitrosoaziridine intermediate. In the second step, this intermediate undergoes cycloreversion through a slightly asynchronous concerted transition state to form an alkene with the same stereochemistry, which is in total agreement with experiment. In the whole reaction, the denitrosation step is found to be rate‐determining. For comparison, geometry optimizations and energies were also obtained at the B3LYP/6‐31G(d) level. It was found that the B3LYP energy results differed significantly from the QCISD ones. To analyze the reason for this difference, B3LYP calculations were repeated by varying the contribution of exact exchange in the Becke functional. With respect to the QCISD results, it has been shown that the functional with 0% exact exchange yields the best activation barriers, whereas the functional with 30% exact exchange is the most suitable one to carry out the complexation and reaction energy calculations. © 2004 Wiley Periodicals, Inc. Int J Quantum Chem, 2005     

Derivatives of condensed thieno[2,3-d]-pyrimidines. 20. Synthesis of 2-substituted 5,6-dihydro-8H-pyrano[4′,3′:4,5]thieno[2,3-d]pyrimidin-4(3H)-ones and 5,6,7,8-tetrahydrobenzo-[b]thieno[2,3-d]pyrimidin-4-ones

We have developed a method for obtaining 2-substituted 3-amino-6,6-dimethyl-5,6-dihydro-8H-pyrano[4′,3′:4,5]-and 5,6,7,8-tetrahydrobenzo[b]thieno[2,3-d]pyrimidin-4(3H)-ones, converted by deamination to the corresponding dihydropyranothieno-3H-pyrimidinones. __________ Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 3, pp. 441–444, March, 2006.     

固定化D-氨基酸氧化酶催化DL-氨基酸去消旋化制备非天然L-氨基酸

在过氧化氢酶和氧气存在下,固定化D-氨基酸氧化酶(D-AAO)对映选择性催化DL-氨基酸中的D-对映体氧化脱氨为相应酮酸,L-对映体保留.研究了D-AAO的底物特异性并对反应条件进行了优化.结果表明:D-AAO具有较宽的底物谱,能够催化疏水性α-氨基酸的D-对映体氧化脱氨.在最优反应条件下,D-AAO催化DL-2-氨基丁酸、DL-2-氨基戊酸去消旋化,L-2-氨基丁酸、L-2-氨基戊酸的收率分别为48%和47%,ee分别为99.5%和99.8%.进一步地利用Pd-C/HCOONH4催化氧化脱氨过程中产生的亚氨基酸原位还原,有效提高了L-2-氨基丁酸、L-2-氨基戊酸的收率并保持高的光学纯度.     

Obituary: Professor Dr.-Ing. Justus Mühlenpfordt

Abstract

The dose-dependent isotope fractionation during decarboxylation (¹³C/¹²C) amplifies the radiation effect in the relatively low dose range. The fractionation of the nitrogen isotopes during deamination (¹⁵N/¹⁴N) at the dose of 17 Gy was found to be smaller than that of decarboxylation.     

Nuclear Magnetic Resonance (NMR) Spectroscopy: A Review and a Look at Its Use as a Probative Tool in Deamination Chemistry

Abstract

This year (2006) represents the 60th anniversary of nuclear magnetic resonance (NMR) spectroscopy (discovered independently by Nobel laureates Edward Purcell and Felix Bloch). It is therefore appropriate and indeed valuable to reflect on how this versatile methodology has developed, expanded, and evolved into a cornerstone of chemical research since 1946. No doubt multiple reviews discussing various aspects of NMR technology will emerge over the course of this year, but the field has grown so exponentially since its inception that it would be impossible for a single review to meaningfully encompass all features of the NMR methodology. This work, therefore, is not meant to provide a comprehensive review of NMR spectroscopy (such an undertaking would prove unwieldy and is inapt in the current context). Instead, it will provide an overview of NMR spectroscopy including the basic principles of NMR (the NMR phenomenon, instrumentation, and spectral interpretation) the historical development of the field, and a few unique applications of the methodology. Finally, illustrations of the utility and application of NMR spectroscopy as a probative tool in the intriguing field of deamination chemistry will be examined. Among the examples highlighted are the elucidation of the mechanism of N‐nitrosoamide conversion to the trans‐diazotate ester, denitrosation under near‐neutral conditions, elucidation of the bond‐forming step of Friedel‐Crafts benzylation, and the identification of novel electronic (π?‐acceptor agostic‐type interaction) and steric (persisteric) effects.     

胞嘧啶脱氨基化酶APOBEC3家族及其与核酸复合物结构研究进展

载脂蛋白B mRNA催化编辑蛋白APOBEC3（简称为A3）是细胞内逆转录转座子防御系统中一类家族蛋白,它通过对底物单链DNA和RNA中胞嘧啶的脱氨基化在人类的健康和疾病中发挥多种多样的作用.部分人源A3家族蛋白通过对病毒基因组中的胞嘧啶脱氨基化产生尿嘧啶,使逆转录病毒人类免疫缺陷病毒（HIV-1）基因组发生G→A碱基突变,致使HIV-1基因组不能执行正常的功能而抑制HIV-1病毒复制.作为反保护措施,HIV-1病毒利用自身的Vif蛋白（viral infectivity factor）结合人源A3蛋白,通过泛素化标记使A3蛋白降解,从而保证病毒感染.为更好理解A3蛋白催化胞嘧啶脱氨基化机制及抗病毒机制,综述了A3家族蛋白结构、它们对DNA或者RNA进行脱氨基化反应特点和它们与核酸复合物结构的研究进展,对A3家族蛋白参与脱氨基化反应的关键残基如何与核酸碱基相互作用等作了简单概括,相互作用的共同特征进行简要总结,对后期如何利用冷冻电镜技术开展全长A3蛋白相关工作做了展望.本文也部分讨论了A3蛋白如何与Vif相互作用,因此本综述对针对这些相互作用合理设计抗病毒药物有一定帮助.     

Copper‐Catalyzed Deaminative Difluoromethylation

The difluoromethyl group (CF₂H) is considered to be a lipophilic and metabolically stable bioisostere of an amino (NH₂) group. Therefore, methods that can rapidly convert an NH₂ group into a CF₂H group would be of great value to medicinal chemistry. We report herein an efficient Cu‐catalyzed approach for the conversion of alkyl pyridinium salts, which can be readily synthesized from the corresponding alkyl amines, to their alkyl difluoromethane analogues. This method tolerates a broad range of functional groups and can be applied to the late‐stage modification of complex amino‐containing pharmaceuticals.     

Deamination of the amino acid fragment in imine metallacycles: unexpected synthesis of an NH-aldimine organometallic compound

We report that the action of Lewis bases, such as triphenylphosphine, pyridine, or trimethylamine, on imine metallacycles derived from amino acids leads to the formation of the first organometallic compound of an NH aldimine, a highly reactive organic species, and the corresponding alpha-ketoester, in a deamination reaction that mimics the metabolism of alpha-amino acids. The synthesis of different cyclopalladated compounds by a reaction between palladium acetate and the Schiff bases 2,4,6-Me(3)C(6)H(2)CH=NCH(R(1))COOR(2) (R(1) = CH(2)Ph, R(2) = Et and R(1) = Ph, R(2) = Me) is also reported.     

A quantitative model of error accumulation during PCR amplification

The amplification of target DNA by the polymerase chain reaction (PCR) produces copies which may contain errors. Two sources of errors are associated with the PCR process: (1) editing errors that occur during DNA polymerase-catalyzed enzymatic copying and (2) errors due to DNA thermal damage. In this study a quantitative model of error frequencies is proposed and the role of reaction conditions is investigated. The errors which are ascribed to the polymerase depend on the efficiency of its editing function as well as the reaction conditions; specifically the temperature and the dNTP pool composition. Thermally induced errors stem mostly from three sources: A+G depurination, oxidative damage of guanine to 8-oxoG and cytosine deamination to uracil. The post-PCR modifications of sequences are primarily due to exposure of nucleic acids to elevated temperatures, especially if the DNA is in a single-stranded form. The proposed quantitative model predicts the accumulation of errors over the course of a PCR cycle. Thermal damage contributes significantly to the total errors; therefore consideration must be given to thermal management of the PCR process.