《应用生物催化》特色教学内容概览

《应用生物催化》是生物化工专业的核心课程。其研究为化学、医药、食品等领域高附加值产品的生产奠定基础。生物催化的特色教学领域包括非水相体系、手性物质合成、定向进化和极端微生物等方面。应用生物催化核心教学内容的归纳与总结,将有助于学生快速掌握本学科的知识体系,并为生物化工领域的科研人员提供重要参考资料。     

生物催化技术在手性化合物合成中的应用

生物催化的手性合成是当今手性合成方法研究的热点和发展方向。本文综述了生物催化技术在手性化合物合成中的应用,并对其应用前景进行展望。     

手性功能化离子液体的合成进展

手性离子液体作为功能化离子液体的一种,综合了离子液体与手性物质两方面的特性。不仅具有手性特征,而且几乎无蒸气压,无可燃性,具有很高的热力学和化学稳定性,电导率高,可以循环使用,对无机和有机物有良好的溶解性、稳定性等。手性离子液体可以作为手性溶剂,催化剂载体或手性诱导剂,应用于手性合成、手性分离和手性催化等领域。本文综述了近些年来手性离子液体合成的最新进展,结构上按阴、阳离子分类,同一离子类型中按物质种类分类。同时介绍了一些新的合成技术。最后对手性离子液体可能的发展趋势和以后的研究方向进行了展望。     

酶法制备手性内酯的研究进展

随着手性科学的快速发展,获取手性内酯的单一对映体具有重要的研究和应用价值.酶法合成手性化合物具有催化效率高、立体选择性强、条件温和等优点,已成为目前化工领域研究和应用的热点.综述了当前主要三类酶法制备手性内酯的途径及其应用.     

生物催化技术在精细化工中的应用

近年来,生物催化剂在精细化学品生产中的应用增长很快,精细化工和制药工业消费的生物催化剂在1亿～1.3亿美元/a,预计年增长率达8％～9％。生物催化技术不仅可解决化学法进行不对称合成与拆分所需的手性源以及产生无效对映体引起的环保问题,还可直接用于不对称合成、生产手性化合物以及结构复杂、具有生物活性的大分子和高分子化合物。具有反应条件温和、能源节省、转化率和选择性高、环境友好和投资少等优点的生物化工已成为国外著名化学公司投资的重点。     

手性化合物酶法制备中辅酶再生体系的构建与应用进展

辅酶的再生与反复利用对氧化还原型生物催化剂在手性化合物中的生产具有重要作用。辅酶的酶催化法再生具有高效、专一的特点,根据其催化环境可分为单细胞内辅酶再生体系、双细胞耦合体系及胞外酶耦合体系。本文详细阐述了酶法再生中各种辅酶再生体系的构建方法,特别指出了辅酶再生体系使用中可能遇到的问题并给出了解决方法,如利用离子液体解决有机底物低水溶性的问题,利用共价固定方法解决小分子辅酶的留存问题,无细胞抽提液中内源性辅酶再生酶的利用等。除此之外,对每种辅酶再生方法与体系在工业催化中应用的优势与局限性作了评述,特别关注了辅酶再生体系反复多批次利用的问题。     

过氧化物酶应用的生物技术进展

介绍了过氧化物酶可以催化的四种反应类型 :氧化去氢反应、氧化卤化反应、双氧水歧化反应、氧传递反应。综述了过氧化物酶在有机合成等反应中的应用前景。认为氯过氧化物酶是一种应用最广的过氧化物酶 ,在催化有机反应时 ,具有更高的手性选择性和酶稳定性     

烯烃不对称环氧化反应催化剂的研究进展

综述了手性催化剂催化的不对称环氧化反应研究进展情况。     

离子液体中酶催化反应的研究进展

讨论了近年来离子液体作为酶催化反应介质的应用发展。说明了不同类别的酶在离子液体或水合离子液体两相体系中具有催化活性，尤其是脂肪酶，在无水的离子液体介质反应体系中不仅能保持很好的活性，其手性选择性和操作稳定性往往优于传统介质中的表现。指出了离子液体的环境相容性使其成为绿色生物反应工程新的应用溶剂。对不适于在传统溶剂体系中进行的生物催化再生和产物回收研究，离子液体溶剂已经逐渐表现出其优势。     

芳胺N-单烷基化定向控制工艺进展

芳胺N-单烷基化产物是重要的精细化工产品。本文讨论了金属及其氧化物催化、沸点分子筛催化及相转移催化定向控制合成N-单烷基芳胺的方法及进展情况,并比较了各自的优缺点和发展前景。     

聚苯乙烯树脂的手性修饰

以交联聚苯乙烯为原料树脂,二苯甲酰酒石酸酐为傅—克酰基化反应的酰化试剂合成手性树脂,通过红外光谱和元素分析对该手性树脂进行了表征,研究了溶剂、催化剂、反应温度、反应时间对该手性修饰树脂增重率的影响。     

Continuous Chirality Measure in Reaction Pathways of Ruthenium‐Catalyzed Transfer Hydrogenation of Ketones

Here we report theoretical studies on the ruthenium‐catalyzed reduction of acetophenone (and 2‐hexanone) with the intent of understanding the relative roles of catalyst and substrate along the reaction path. Overall ten reaction pathways are examined. The first eight are for acetophenone: they arise from the presence of two catalysts, with the more enantioselective one labeled 1 , and the poorer one labeled 2 , multiplied by the two configurations that the metal center of the catalysts can assume, multiplied by the two approaches, Re‐ and Si‐side, of the substrate to the catalyst. Two pathways are examined for 2‐hexanone and entail the two approaches to the ketone of the more effective catalyst. Density functional theory calculations provide structures of the minima and transition states, which subsequently have been assessed with the “continuous chirality measure” model developed by Avnir and collaborators. The picture that emerges is that the asymmetric induction is due to the interplay between the organometallic system and the organic substrate. This is effective only for catalyst 1 , which can interact effectively with acetophenone along only one in four of the reaction pathways, but not for 2 for which two out of four pathways are opened. For the hydrogenation of 2‐hexanone, the same catalyst 1 cannot produce enantiomeric excesses because the conformation of the substrate in the transition state induced by the catalyst has a relative low chirality.     

除草剂的手性和除草活性

简要介绍了除草剂的构型和除草活性的关系以及除草剂有效成分的合成方法。     

Flow Effects in Supramolecular Chirality

There are an increasing number of reports on the emergence of circular dichroic signals when solutions of J-aggregates are vortex-stirred. Some authors claim that the transfer of chirality from the macroscopic stirring vortex occurs at the level of electronic transitions. Others argue that the signal observed is not due to true circular dichroism (CD), but rather that it is an artifact due to combinations of linear polarization contributions. For both interpretations it is necessary to assume that the alignment by effect of flows dominates over the Brownian dynamics. Therefore, the topic belongs to supramolecular chemistry because the alignment in current flows can only occur for relatively large particles with an appropriate shape. The phenomenon is detected by CD spectroscopy, which itself is also the main hindrance, even controversial, in its study and interpretation. However, modern Mueller matrix polarimetry can solve some of the problems. The phenomenon has been explained using different scenarios; however, in some of the systems the experimental evidence only supports the model in which deformation (folding/torsion) of elastic soft-matter yields true CD. Here we discuss the role of the gradient of shear rates in the deformation of nano particles of soft matter to give chiral supramolecular structures, as the first step to explaining the phenomenon.     

漫谈化学反应

无处不在的化学反应是化学进化的基础。在生物体内的化学反应有赖于酶的催化。酶是高分子长链的多肽,其作用与整个分子有关,确切的机理有待进一步阐发。     

Probing the Role of Chirality in Phospholipid Membranes

Nucleotides, amino acids, sugars, and lipids are almost ubiquitously homochiral within individual cells on Earth. While oligonucleotides and proteins exist as one natural chirality throughout the tree of life, two stereoisomers of phospholipids have separately emerged in archaea and bacteria, an evolutionary divergence known as “the lipid divide”. Within this review, we focus on the emergence of phospholipid homochirality and compare the stability of synthetic homochiral and heterochiral membranes in vitro. We discuss chemical probes designed to study the stereospecific interactions of lipid membranes in vitro. Overall, we aim to highlight studies that help elucidate the determinants of stereospecific interactions between lipids, peptides, and small molecule ligands. Continued work in understanding the drivers of favorable interactions between chiral molecules and biological membranes will lead to the design of increasingly selective chemical tools for bioorthogonal labeling of lipid membranes and safer membrane-associating pharmaceuticals.     

Recommendations on the Implementation of Genetic Algorithms for the Directed Evolution of Enzymes for Industrial Purposes

In directed evolution (DE) the assessment of candidate enzymes and their modification is essential. In this study we have investigated genetic algorithms (GAs) in this context and conducted a systematic study of the behavior of GAs on 20 fitness landscapes (FLs) of varying complexity. This has allowed the tuning of the GAs to be explored. On the basis of this study, recommendations for the best GA settings to use for a GA‐directed high‐throughput experimental program (in which populations and the number of generations is necessarily low) are reported. The FLs were based upon simple linear models and were characterized by the behavior of the GA on the landscape as demonstrated by stall plots and the footprints and adhesion of candidate solutions, which highlighted local optima (LOs). In order to maximize progress of the GA and to reduce the chances of becoming stuck in a LO it was best to use: 1) a large number of generations, 2) high populations, 3) removal of duplicate sequences (clones), 4) double mutation, and 5) high selection pressure (the two best individuals go to the next generation), and 6) to consider using a designed sequence as the starting point of the GA run. We believe that these recommendations might be appropriate starting points for studies employing GAs within DE experiments.     

手性中间体2,4-二氯-а-氯甲基苯甲醇的合成

[方法]2,4-二氯-α-氯甲基苯甲醇是重要的农药和医药中间体,可用于合成许多重要的农药和医药杀菌剂。以间二氯苯为起始原料,经傅克酰基化反应合成α-氯-2,4-二氯苯乙酮,再经手性催化还原得到α-氯-2,4-二氯苯乙醇。[结果]分别探讨了唑硼烷和唑铝烷催化体系的催化效果,由实验验证唑硼烷催化体系在室温下可使原料基本完全转化,ee值最高达98%。铝的催化效果一般,转化率和ee值均较低。[结论]该路线简单经济,反应条件温和,适合生产。