Knowledge-based systems for analytical chemistry

Analytical chemists have made extensive use of computer technology, automating most analytical instruments, many analyses and reporting activities. We now need to expand the areas to which computers can be applied by addressing problems of greatly increased complexity. These problems fall into two general classes, the first class of problems are those thatcannot be solved using only first principle information and, the second class are those problems thatcan be solved using only first principles, but that are so complex that the traditional approach is often not cost effective.The discussion will center on how artificial intelligence technology (AI) can provide the means for using heuristics together with first principle information to solve instances of the first class of problems. The knowledge required to provide the solution is formulated as facts, rules (heuristics) and an inference engine.The same AI technology can also be used to refine specifications and provide cost effective solutions for very complex problems involving only first principle information. For this class of problems an AI work station can provide the software development conductive to rapid prototyping and specification refinement.Discussion of several expert systems will be used to describe the capabilities and features of rule-based systems. The strengths and weaknesses of one system, use of IR spectra for structure elucidation, will be examined in some detail. It is an expert system consisting of rule sets organized into logic trees, thus it will provide an opportunity to describe how the use of more advanced AI technology could further improve the program's performance.     

Undergraduate Projects in the Application of Artificial Intelligence to Chemistry. I. Background

The potential of Artificial Intelligence (AI) in the development of intelligent machines is widely recognized. It is less widely appreciated that the methods which computer scientists use in their work on AI are also applicable to the solution of numerous problems in science. In many cases, AI methods are preferable to more conventional approaches, being superior in terms of time, quality of solution, or both. Most AI tools are comparatively simple to understand, despite their power, and computer programs to implement them can be written by anyone with average programming skills. This series of papers will demonstrate how AI methods are of value in science, why they work, and how they can be introduced into the syllabus as undergraduate research projects; suggestions of projects, illustrative programs and Java source code will be provided. This paper introduces the topic of AI and explains some of the ways in which an AI program differs from a conventional program.     

Towards the development of synthetic routes using theoretical calculations: an application of in silico screening to 2,6-dimethylchroman-4-one

This study describes an attempt to develop a synthetic route using theoretical calculations, i.e., in silico synthesis route development. The KOSP program created four potential synthetic routes for generating 2,6-dimethylchroman-4-one. In silico screening of these four synthetic routes was then performed. In silico screening involves theoretical analysis of synthetic routes prior to actual experimental work. A synthetic route using the Mitsunobu reaction had already been reported by Hoddgets et al. Theoretical investigations were also conducted on two S(N)Ar reactions as well as a Michael reaction before they were examined experimentally. In silico screening using DFT calculations indicated that only the Michael reaction was likely to produce the target. Experimental work confirmed that the target was obtained in a yield of 76.4% using the Michael reaction. The other two routes, except for the Mitsunobu reaction, failed to generate the target. Our results demonstrate that theoretical calculations can be used to narrow down the number of experiments that need to be conducted when developing novel synthetic routes.     

Microwave reactions under continuous flow conditions

Microwave chemistry has already impacted significantly on the everyday synthesis of organic molecules. The adoption and integration of this liberating technology has permitted a resurrection of many synthetic transformations that were previously considered too extreme in their conditions (temperatures, pressures, reaction times) to be synthetically useful. Furthermore, whole arrays of additional chemical transformations have been devised under microwave heating that allow access to more diverse chemical architectures via more expedient routes. Continuous flow processing of chemical intermediates taking advantage of the unique heating mechanism and characteristics of microwave irradiation will certainly be the next evolutionary step forward in this area. The synergistic combination afforded by the simultaneous application of these two core processing tools will enhance still further the synthetic capabilities of tomorrow's chemists. This short review aims to highlight the current developments and future potential offered by continuous flow microwave mediated synthesis.     

手性炔丙醇的不对称催化合成研究进展

手性炔丙醇是一种重要中间体化合物,作为合成多种光学活性化合物的重要合成前体受到学者们广泛关注。目前通过酮的不对称催化反应合成手性炔丙醇的研究开发具有极大发展前景,因此本文围绕酮类化合物的不对称催化反应来进行综述,结合相关反应最新研究进展,全面总结并分类了不对称催化还原、催化不对称加成等反应类型,介绍了合成不同结构手性炔丙醇的新思路,并对酮的不对称催化反应在未来能成为工业化重要生产途径作出展望。     

On the interplay between theory and experiment in molecular structure problems: Some case studies

Some brief, general comments on the concept of molecular structure will be given. Some important points connected to the use of models in the interpretation of molecular structures will also be mentioned. The main theme in one part of the presentation will be the cooperative efforts made by experimentalists (mainly spectroscopists) and theoreticians (computational chemists) in order to measure, predict, and analyze the perturbations on the cyclopropane ring by different substituents. The aim is to demonstrate that ab initio calculations of a certain quality can constitute an important support for experimental studies in that they are able to discriminate between different models that otherwise are equally probable. The second part of the presentation will be concerned with a class of molecules that gives both experimental structural chemists and computational chemists a great challenge, namely, the metallocenes. A discussion of some of the grave discrepancies between theory and experiment regarding their geometry will be given.     

Recent trends in the synthesis of 1,2,3-thiadiazoles

Abstract

1,2,3-Thiadiazoles, structurally active pharmacophores have attracted significant attention of synthetic chemists, medicinal and pharmaceutical researchers because of their versatile biological activities against various diseases such as herbicidal, insecticidal, antiviral, antitumor, antimicrobial, anticancer, plants activator and anti-amoebic activities. A literature survey of the last decade presented in this review article summarizes the major synthetic approaches, methodologies and strategies adopted for the synthesis of 1,2,3-thiadiazole scaffolds which will be help for medicinal chemists and pharmacists in future synthesis and development of novel therapeutic agents.     

Catalytic Asymmetric Hetero-Diels-Alder Reactions of Carbonyl Compounds and Imines

Asymmetric catalysis is a challenge for chemists: How can we design catalysts to achieve the goal of forming optically active compounds? This review provides the reader with an overview of the development of catalytic asymmetric hetero-Diels-Alder reactions of carbonyl compounds and imines. Since its discovery, the Diels-Alder reaction has undergone intensive development and is of fundamental importance for synthetic, physical, and theoretical chemists. The Diels-Alder reaction has been through different stages of development, and at the beginning of the 21st century catalytic Diels-Alder reactions are one of the main areas of focus. The preparation of numerous compounds of importance for our society is based on cycloaddition reactions to carbonyl compounds and imines. There are several parallels between the reactions of carbonyl compounds and those of imines, which, however, begin to vanish on entering the field of catalytic reactions. Why? From a mechanistic point of view some similarities can be drawn, but the synthetic development of catalytic enantioselective hetero-Diels-Alder reactions of imines are several years behind those of the carbonyl compounds. For hetero-Diels-Alder reactions of carbonyl compounds there a number of different chiral catalysts, and great progress has been achieved in developing enantioselective reactions for unactivated and activated carbonyl compounds. In contrast the development of catalytic enantioselective hetero-Diels-Alder reactions of imines is in its infancy and only few catalytic reactions have been published. This review will focus on the most important developments, and discuss the synthetic and mechanistic aspects of enantioselective hetero-Diels-Alder reactions of carbonyl compounds catalyzed by chiral Lewis acids. For the hetero-Diels-Alder reactions of imines, the diastereoselective reactions of optically substrates catalyzed by Lewis acids will be presented first, followed by the catalytic enantioselective reactions.     

Superstructure searching algorithm for generic reaction retrieval

Chemical reaction knowledge is usually summarized and retrieved by chemists from references, journals, and reaction databases. To rigorously extract chemical reaction knowledge from large data sets, computer algorithms become much more important. This paper presents a new approach, superstructure searching (SSS) algorithm, for generic reaction retrieval. The algorithm considers all known reaction patterns from the targeted structure and assigns synthetic routes for new chemical compounds. This algorithm consists of screening, atom-by-atom comparison, and computation of R-groups' similarity.     

Fluorine chemistry at the millennium

In this “perspective” paper, some of the landmark discoveries and accomplishments of the past within the field of fluorine chemistry will be reviewed. Within this review, the dramatic changes (and growth in size and diversity) that the field has undergone, particularly over the last 50 years, will also be discussed. Then finally, where fluorine chemistry is and where it appears to be going will be briefly discussed. The future of fluorine chemistry indeed appears bright, with fluorine chemistry set to play a role, and usually a significant role in most important areas of technology of the 21st century. New perspectives will be required, but then, fluorine chemists have been providing such “new perspectives” to this ever-changing field for the last 75 years.     

Asymmetric transfer hydrogenation: chiral ligands and applications

Hydrogen transfer reduction processes are attracting increasing interest from synthetic chemists in view of their operational simplicity and high selectivity. In this tutorial review the most significant advances recently achieved in the stereoselective reduction of unsaturated organic compounds catalyzed by homogeneous transition metal complexes are critically reviewed. A sharp growth of the synthetic applications of this technique in the synthesis of fine chemicals is predictable as the use of transition metal catalyzed reactions will become more familiar to synthetic chemists.     

The Pauson-Khand reaction, a powerful synthetic tool for the synthesis of complex molecules

There are still some synthetic chemists who hesitate to use metal-mediated or -catalysed reactions. The Pauson-Khand reaction (PKR) is a powerful transformation that has now been sufficiently well developed to be routinely considered when planning a synthesis, especially of polycyclic complex molecules. This tutorial review aims to encourage the use of this process explaining the best ways of performing a PKR both in the stoichiometric and the catalytic version, showing the scope of the process and its limitations. Additionally, asymmetry can be introduced in the reaction using several strategies, which will be discussed. The most recent examples of the synthetic applications of the PKR in natural product synthesis will give the reader an idea of the great usefulness of this reaction.     

RASA: a rapid retrosynthesis-based scoring method for the assessment of synthetic accessibility of drug-like molecules

In this account, a rapid retrosynthesis-based scoring method for the assessment of synthetic accessibility of drug-like molecules, called RASA (Retrosynthesis-based Assessment of Synthetic Accessibility) is devised. RASA first constructs a synthesis tree for the target molecule based on retrosynthetic analysis; in this process a series of strategies are suggested for limiting combinatorial explosion of the synthesis tree. A scoring function (RASA-score) for the assessment of synthetic accessibility is then proposed based on the optional effective synthetic routes, the complexity of reaction, and the difficulty of separation/purification associated with the most favorable synthetic route. The contributions of individual components are calibrated by linear regression analysis based on the synthetic accessibility estimates of a training set (100 compounds) given by a group of medicinal chemists (G1). Two external test sets (TS1 and TS2), whose synthetic accessibility estimates were given by the group G1 medicinal chemists and another group (G2) of medicinal chemists (from literature), respectively, were adopted for the evaluation of RASA. The correlation coefficient between the calculated RASA-score values and the estimated scores by medicinal chemists for TS1 is 0.807 and that for TS2 is 0.792, which demonstrate the validity and reliability of RASA. The validity and reliability as well as the high speed of RASA and its capability of suggesting synthetic routes enable it a useful tool in drug discovery.     

Microreactors as Tools for Synthetic Chemists—The Chemists' Round‐Bottomed Flask of the 21st Century?

Will microreactors replace the round‐bottomed flask to perform chemical reactions in the near future? Recent developments in the construction of microstructured reaction devices and their wide‐ranging applications in many different areas of chemistry suggest that they can have a significant impact on the way chemists conduct their experiments. Miniaturizing reactions offers many advantages for the synthetic organic chemist: high‐throughput scanning of reaction conditions, precise control of reaction variables, the use of small quantities of reagents, increased safety parameters, and ready scale‐up of synthetic procedures. A wide range of single‐ and multiphase reactions have now been performed in microfluidic‐based devices. Certainly, microreactors cannot be applied to all chemistries yet and microfluidic systems also have disadvantages. Limited reaction‐time range, high sensitivity to precipitating products, and new physical, chemical, and analytical challenges have to be overcome. This concept article presents an overview of microfluidic devices available for chemical synthesis and evaluates the potential of microreactor technology in organic synthesis.     

The Bellus-Claisen rearrangement

Among the reactions available to synthetic chemists for the construction of new C--C bonds, the Claisen rearrangement is one of the most powerful, elegant, and well-characterized methods. A genuinely new variant, the Bellus-Claisen rearrangement came to light a quarter of a century ago: The reaction of an allylic ether, thioether, or amine with a ketene leads through a [3,3] sigmatropic bond reorganization of a zwitterionic intermediate to an E unsaturated ester, thioester, or amide. When applied to cyclic allylic substrates, a ring-enlargement by four carbon atoms in one step provides medium-ring unsaturated E-configured lactones, thiolactones, and lactams. The scope of the Bellus-Claisen rearrangement and the optimum reaction conditions will be discussed in this Minireview.     

The Baylis-Hillman reaction: a novel concept for creativity in chemistry

This tutorial review highlights the way in which the Baylis-Hillman reaction has been increasingly attracting the attention of synthetic and medicinal chemists; it not only helps in originating new ideas to create novel methodologies and molecules but also offers intellectual challenges to understand and address the present day needs in the areas of organic and medicinal chemistry.     

Stereoselective Remote Functionalization via Palladium-Catalyzed Redox-Relay Heck Methodologies

Exploration of novel, three-dimensional chemical space is of growing interest in the drug discovery community and with this comes the challenge for synthetic chemists to devise new stereoselective methods to introduce chirality in a rapid and efficient manner. This Minireview provides a timely summary of the development of palladium-catalyzed asymmetric redox-relay Heck-type processes. These reactions represent an important class of transformation for the selective introduction of remote stereocenters, and have risen to prominence over the past decade. Within this Minireview, the vast scope of these transformations will be showcased, alongside applications to pharmaceutically relevant chiral building blocks and drug substances. To complement this overview, a mechanistic summary and discussion of the current limitations of the transformation are presented, followed by an outlook on future areas of investigation.     

Novel pseudo-delocalized anions for lithium battery electrolytes

A novel anion concept of pseudo-delocalized anions, anions with distinct positive and negative charge regions, has been studied by a computer aided synthesis using DFT calculations. With the aim to find safer and better performing lithium salts for lithium battery electrolytes two factors have been evaluated: the cation-anion interaction strength via the dissociation reaction LiAn ? Li(+) + An(-) and the anion oxidative stability via a vertical ionisation from anion to radical. Based on our computational results some of these anions have shown promise to perform well as lithium salts for modern lithium batteries and should be interesting synthetic targets for future research.     

Fast semiempirical calculations

Most quantum chemists regard semiempirical methods as ephemeral and computationally cost efficient. For this reason, an article dealing with computational efficiency of semiempirical methods is probably very unfashionable. However, experience at a big computer installation, shared by ab-initio and semiempirical quantum chemists shows that the second group actually consumes more computer time than the first. Obviously, the greater size of the molecules in semiempirical calculations outweighs the inherent efficiency of these methods. The present article describes a simple method for accelerating SCF -type semiempirical methods.