<有机合成化学及近代技术>简介

由徐家业主编、西北工业大学出版社出版(1997)的<有机合成化学及近代技术>与流行的同类书籍通常偏重于介绍有机合成反应或各类有机化合物的合成方法不同.该书在按化合物的分子骨架构成,和官能团的变换为纲简要地介绍有机合成反应的同时,较全面的介绍了各种近代有机合成方法和技术.包括有机合成设计、有机电化学合成、相转移催化技术、固相合成方法和干法合成等.除了通常的加热促进反应之外,还介绍了光促反应、微波促进反应和声波促进反应,以及生物催化剂的应用和仿生合成法等,展示了有机合成的新面貌.针对有机合成的实用性,还特意编写了"有机合成的化工过程开发"一章,是一本别具风格的有机化学参考书.     

基于环糊精模板法的有机合成

利用"模板"理念综述了基于环糊精模板法的有机合成反应,并将基于环糊精模板法的有机合成反应分为两大类.第一类是基于环糊精"静态模板法"的有机合成,主要是指以环糊精刚性结构主、次面和空腔为模板进行的有机反应.其中,基于环糊精主次面的有机反应主要是体现了模板效应对空间结构的限定.而基于环糊精空腔的有机反应,重点是介绍那些利用环糊精空腔的手性和空间限定性等特点进行化学选择、区域选择和立体选择的反应,这体现了模板效应中的"信息"传递性.第二类有机反应则是基于"动态模板法",该模板自身是可调控的.其中,既可以具有可变空间构象的桥连环糊精二聚体为模板,也可以环糊精衍生物以及环糊精主客体包合物的自组装体系为模板.     

芳基锡烷的合成研究进展

芳基锡烷化合物是参与构筑功能分子中芳基碳碳键和碳杂原子键的一类重要合成中间体. 其在药物化学、材料科学以及有机合成中都具有重要应用, 因此发展其高效新颖的合成方法具有重要的意义. 根据反应机理的类型, 综述了近些年来合成芳基锡烷的方法, 包括(1)芳香亲核试剂的锡化反应; (2)芳香亲电试剂的锡化反应; (3)过渡金属催化的锡化偶联反应; (4)芳基自由基中间体介导的锡化反应; (5)炔烃的环化和串联的锡化反应. 最后, 进一步分析了未来合成芳基锡烷的研究趋势.     

催化的不对称二羟基化反应

综述了不对称二羟基化反应的一般原理、反应历程，介绍了常用配体的种类、合成方法、应用范围和反应条件以及不对称二羟基化反应在有机合成中的应用。     

DNA催化水相体系中的二硫缩醛反应(英文)

在各种生命起源假说中,比较公认的是原生生命起源于RNA.在RNA世界中,RNA不仅是遗传物质,并且是具有酶活性的催化剂.DNA在自然界中普遍以双螺旋结构存在,一直被认为只是生命体遗传信息的载体,但是DNA和RNA相似的化学组成引发了研究者探究DNA是否具有催化功能.尽管到目前为止在自然界还没有发现具有催化活性的DNA,研究者利用有机反应模型已经开展研究DNA的相关催化功能,例如利用DNA为模板进行有机合成和利用DNA的手性结构进行手性合成.但是,直接利用DNA作为催化剂进行有机反应的研究还不多见.本文报道了源于鲱鱼精的双链DNA可以催化水相体系中一系列醛的二硫缩醛反应.通过实验推断DNA中的磷酸基团为主要的催化活性中心,并且DNA的双螺旋结构对反应也起到一定的促进作用.     

炔丙醇与二硫缩烯酮的[3+2]环加成反应

正环戊二烯是一类独特的五元碳环化合物,在有机合成以及过渡金属催化领域有重要应用.利用易得的原料发展简便的合成新方法,尤其是制备高度官能化的环戊二烯仍然是当前有机合成化学研究的重要课题.二硫缩烯酮是一类易于制备的有机合成中间体,具有上百年的研究历史.然而,作为极化的两碳合成子,它主要应用于杂环类化合物合成,其间经历经典的烷硫基取代反应;迄今为止,尚未有应用于[2+x]型合成碳环的研究报道.近期,东北师范     

模板合成新进展

介绍了模板的合成的定义，来源，分类以及有机合成，蛋白质合成中的应用。     

不饱和烃杂钯化反应在有机合成中的应用

不饱和烃杂钯化反应是合成高活性反应中间体烷基钯(II)和烯丙基钯(II)重要的途径. 这些钯的络合物, 在合适的条件下能被各种亲核试剂例如烯丙基卤、一氧化碳、不饱和烃、有机硼、有机锡等捕获. 经过一系列插入及消除反应, 能够有效地构建多种生理活性药物、有机功能分子以及重要合成骨架. 近年来, 引起了有机合成工作者的兴趣. 在这里, 对杂钯化最新进展进行综述.     

手性路易斯碱和过渡金属协同催化反应的进展

近年来过渡金属与以苯并四咪唑类化合物为代表的手性路易斯碱协同作用下的不对称催化反应取得了重要的进展,包括芳基醋酸酯α衍生化及乙内酰脲、二氢喹啉酮等结构的合成、双手性中心烯丙基化反应和α-氨基酸衍生物合成等.这些反应在有机合成中有广阔的应用前景.本文将对这类反应的研究进展做简要的介绍.     

N-磺基脒类化合物合成研究进展

脒类化合物因其独特的偕二氮结构,在合成含氮化合物方面具有重要作用.作为脒类化合物中独特的一类,N-磺基脒类化合物更是多种重要有机合成反应的关键中间体,在现代有机合成中占有举足轻重的位置.基于这一背景,对N-磺基脒类化合物的合成进展进行了综述.依据反应特点,分别基于胺氧化酰化反应、炔-叠氮-胺三组分反应、烯胺碳-碳键官能化、酰胺活化以及其它相关的反应等方面的研究进展进行介绍,以期为相关领域的研究工作提供指导作用.     

Translation of DNA into synthetic N-acyloxazolidines

The translation of DNA into synthetic molecules enables their manipulation by powerful evolution-based methods previously available only to proteins and nucleic acids. The development of increasingly sophisticated DNA-templated small-molecule syntheses is crucial to broadening the scope of this approach. Here, we report the translation of DNA templates into monocyclic and bicyclic N-acyloxazolidines using multistep DNA-templated organic synthesis. Second-generation template architectures, used for the first time in a multistep DNA-templated synthesis, together with reactions and linker cleavage strategies not previously described in a DNA-templated format, were crucial to the successful translation. The products generated in this work represent the most complex small molecules to date synthesized in a DNA sequence-programmed manner and provide the basis for DNA-templated synthetic heterocycle libraries.     

DNA-templated functional group transformations enable sequence-programmed synthesis using small-molecule reagents

DNA-templated organic synthesis (DTS) has previously been used primarily to direct coupling reactions between two DNA-linked reactants. In some cases, reactants are difficult or impossible to tether to DNA oligonucleotides. The development of strategies that enable non-DNA linked small-molecule reagents to participate in sequence-programmed synthesis therefore would significantly expand the capabilities of DTS. We developed efficient DNA-templated functional group transformations of template-linked azides into corresponding amines, carboxylic acids, and thiols. The application of these reactions to a single-solution mixture of four template-linked organic azides enabled each azide to be transformed sequence specifically into a sulfonamide, carbamate, urea, or thiourea using small-molecule sulfonyl chloride, chloroformate, isocyanate, or isothiocyanate reagents not tethered to DNA. Only the four desired products were observed, without formation of any of the 12 possible undesired cross-products. Our results represent a new approach to small molecule diversification in a DNA-programmed manner.     

Effects of template sequence and secondary structure on DNA-templated reactivity

DNA-templated organic synthesis enables the translation, selection, and amplification of DNA sequences encoding synthetic small-molecule libraries. As the size of DNA-templated libraries increases, the possibility of forming intramolecularly base-paired structures within templates that impede templated reactions increases as well. To achieve uniform reactivity across many template sequences and to computationally predict and remove any problematic sequences from DNA-templated libraries, we have systematically examined the effects of template sequence and secondary structure on DNA-templated reactivity. By testing a series of template sequences computationally designed to contain different degrees of internal secondary structure, we observed that high levels of predicted secondary structure involving the reagent binding site within a DNA template interfere with reagent hybridization and impair reactivity, as expected. Unexpectedly, we also discovered that templates containing virtually no predicted internal secondary structure also exhibit poor reaction efficiencies. Further studies revealed that a modest degree of internal secondary structure is required to maximize effective molarities between reactants, possibly by compacting intervening template nucleotides that separate the hybridized reactants. Therefore, ideal sequences for DNA-templated synthesis lie between two undesirable extremes of too much or too little internal secondary structure. The relationship between effective molarity and intervening nucleic acid secondary structure described in this work may also apply to nucleic acid sequences in living systems that separate interacting biological molecules.     

A modular approach to DNA-programmed self-assembly of macromolecular nanostructures

DNA-programmed organic reactions are new and powerful tools for assembling chemical compounds into predetermined complex structures and a brief review of their use is given. This approach is particular efficient for the selection and covalent coupling of multiple components. DNA-templated synthesis is used for polymerization of PNA tetramers and for copying of the connectivity information in DNA. Direct DNA-programmed multicomponent coupling of custom designed organic modules is described. The macromolecular structures obtained are highly conjugated potentially conducting nanoscaffolds. Some future developments in this area are discussed.     

Stereoselectivity in DNA-templated organic synthesis and its origins

DNA-templated synthesis is a surprisingly general strategy for controlling chemical reactivity that enables synthetic products to be manipulated in ways previously available only to biological macromolecules. The chiral nature of the DNA template raises the possibility that DNA-templated synthesis can proceed stereoselectively. Here, we show that DNA-templated substitution reactions can exhibit stereoselectivity without the assistance of chiral groups other than those present in DNA. By characterizing changes in stereoselectivity as a result of systematic changes in the structure of the template-reagent complexes, we begin to reveal the origins of the observed stereoselectivity. We propose that the conformations of nucleotides adjacent to the reactants are largely responsible for stereoselectivity. Indeed, template and reagent sequences that can adopt either a left-handed Z-form DNA helix or a normal right-handed B-form DNA helix generate opposite stereoselectivities in the Z-form and B-form even though they share the same covalent structure and the same absolute stereochemistry. Our findings establish ways in which the chirality of an information carrier can be transmitted to the stereochemistry of encoded products through templated synthesis.     

Multistep small-molecule synthesis programmed by DNA templates

The translation of DNA sequences into synthetic products is a key requirement of our approach to evolving synthetic molecules through iterated cycles of translation, selection, and amplification. Here we report general linker and purification strategies for sequence-specific DNA-templated synthesis that collectively enable the product of a DNA-templated reaction to be isolated and to undergo subsequent DNA-templated reactions. Using these strategies, we have achieved the first multistep nucleic acid-templated small-molecule syntheses to generate two different molecules. In addition to representing a method for translating DNA templates sequence-specifically into corresponding multistep synthetic products, our findings also provide experimental support for previously proposed models invoking multistep nucleic acid-templated synthesis as mediating the prebiotic translation of replicable information into the earliest functional molecules.     

Translation of DNA into a library of 13,000 synthetic small-molecule macrocycles suitable for in vitro selection

DNA-templated organic synthesis enables the translation, selection, and amplification of DNA sequences encoding synthetic small-molecule libraries. Previously we described the DNA-templated multistep synthesis and model in vitro selection of a pilot library of 65 macrocycles. In this work, we report several key developments that enable the DNA-templated synthesis of much larger (>10,000-membered) small-molecule libraries. We developed and validated a capping-based approach to DNA-templated library synthesis that increases final product yields, simplifies the structure and preparation of reagents, and reduces the number of required manipulations. To expand the size and structural diversity of the macrocycle library, we augmented the number of building blocks in each DNA-templated step from 4 to 12, selected 8 different starting scaffolds which result in 4 macrocycle ring sizes and 2 building-block orientations, and confirmed the ability of the 36 building blocks and 8 scaffolds to generate DNA-templated macrocycle products. We computationally generated and experimentally validated an expanded set of codons sufficient to support 1728 combinations of step 1, step 2, and step 3 building blocks. Finally, we developed new high-resolution LC/MS analysis methods to assess the quality of large DNA-templated small-molecule libraries. Integrating these four developments, we executed the translation of 13,824 DNA templates into their corresponding small-molecule macrocycles. Analysis of the resulting libraries is consistent with excellent (>90%) representation of desired macrocycle products and a stringent test of sequence specificity suggests a high degree of sequence fidelity during translation. The quality and structural diversity of this expanded DNA-templated library provides a rich starting point for the discovery of functional synthetic small-molecule macrocycles.     

Peptidomimetic bond formation by DNA-templated acyl transfer

The efficiencies of DNA-templated acyl transfer reactions between a thioester modified oligonucleotide and a series of amine and thiol based nucleophiles are directly compared. The reactivity of the nucleophile, reaction conditions (solvent, buffer, pH) and linker length all play important roles in determining the efficiency of the transfer reaction. Careful optimisation of the system enables the use of DNA-templated synthesis to form stable peptide-like bonds under mild aqueous conditions close to neutral pH.     

Template-directed ligation on repetitive DNA sequences: a chemical method to probe the length of Huntington DNA

Several genomic disorders are caused by an excessive number of DNA triplet repeats. We developed a DNA-templated reaction in which product formation occurs only when the number of repeats exceeds a threshold indicative for the outbreak of Chorea Huntington. The combined use of native chemical PNA ligation and auxiliary DNA probes enabled reactions on templates obtained from human genomic DNA.     

DNA meets synthetic polymers--highly versatile hybrid materials

The combination of synthetic polymers and DNA has provided biologists, chemists and materials scientists with a fascinating new hybrid material. The challenges in preparing these molecular chimeras were overcome by different synthetic strategies that rely on coupling the nucleic acid moiety and the organic polymer in solution or on solid supports. The morphologies and functions of the bioorganic block copolymers can be controlled by the nature of the synthetic polymer segment as well as by the sequence composition and length of the DNA. Recent developments have expanded the scope and applications of these hybrid materials in a number of different areas including biology and medicine, as well as bio- and nanotechnology. Their usage ranges from gene delivery through to DNA detection to programmable nano-containers for DNA-templated organic reactions.