[Basic Study on Organic Electron Transfer Reactions by Electrochemistry Combined with Quantum Chemical Calculations].

This review summarizes the results of the author's basic research on organic electrochemistry conducted at Gifu Pharmaceutical University over about 40 years. After completing graduate school, the author became a research associate in Prof. Tanekazu Kubota's laboratory and started research on molecular spectroscopy in 1983. After Prof. Kubota retired in 1989, the author continued investigations in the field of organic electrochemistry as an independent researcher. At that time, a research environment in which ab initio molecular orbital calculations can be used as an analytical tool for experimental research was developed, and the author commenced research on organic electrochemistry combined with quantum chemical calculations as a lifework. The author's research topics were basic research on the molecular theory of redox potentials of organic molecules, molecular design of functional molecules, intermolecular interactions of organic molecules involving electron transfers and electron transfer systems composed of bioactive quinones, and analytical application research based on the basic electrochemistry. In this review article, the essence of the research results is introduced while reflecting on the existing situation at the time of the research. The author concludes the review by expressing gratitude to all colleagues for supporting the research in the author's laboratory.

A One-Pot Approach to Novel Pyridazine C-Nucleosides.

The synthesis of glycosides and modified nucleosides represents a wide research field in organic chemistry. The classical methodology is based on coupling reactions between a glycosyl donor and an acceptor. An alternative strategy for new C-nucleosides is used in this approach, which consists of modifying a pre-existent furyl aglycone. This approach is applied to obtain novel pyridazine C-nucleosides starting with 2- and 3-(ribofuranosyl)furans. It is based on singlet oxygen [4+2] cycloaddition followed by reduction and hydrazine cyclization under neutral conditions. The mild three-step one-pot procedure leads stereoselectively to novel pyridazine C-nucleosides of pharmacological interest. The use of acetyls as protecting groups provides an elegant direct route to a deprotected new pyridazine C-nucleoside.

[Overview of 43 Years of Studies on Asymmetric Synthesis].

Our investigations of various aspects of organic chemistry over the past 43 years are reviewed in this paper. The following subjects are discussed: 1) the diastereoselective addition reaction to chiral imines and oxazolidines of organometallic reagents and its applications and 2) the reaction and synthesis of fluorine-containing compounds.

Soft-Mechanochemistry: Mechanochemistry Inspired by Nature.

Cells and bacteria use mechanotransduction processes to transform a mechanical force into a chemical/biochemical response. The area of chemistry where chemical reactions are induced by mechanical forces is called mechanochemistry. Over the last few years, chemists developed force-induced reactions affecting covalent bonds in molecules under tension which requires high energy input and/or high intensity forces. In contrast, in nature, mechanotransduction processes take place with forces of much weaker intensity and much less demanding energy. They are mainly based on protein conformational changes or changes in supramacromolecular architectures. Mechanochemistry based on such low-energy-demanding processes and which does not affect chemical bonds can be called soft-mechanochemistry. In this feature article, we first discuss some examples of soft-mechanochemistry processes encountered in nature, in particular, cryptic sites, allowing us to define more precisely the concepts underlying soft-mechanochemistry. A series of examples, developed over the past few years, of chemomechanoresponsive systems based on soft-mechanochemistry principles are given. We describe, in particular, cryptic site surfaces, enzymatically active films whose activity can be modulated by stretching and films where stretching induces changes in their fluorescence properties. Finally, we give our view of the future of soft-mechanochemistry.

Recent Discoveries and Future Challenges in Atmospheric Organic Chemistry.

Earth's atmosphere contains a multitude of organic compounds, which differ by orders of magnitude regarding fundamental properties such as volatility, reactivity, and propensity to form cloud droplets, affecting their impact on global climate and human health. Despite recent major research efforts and advances, there are still substantial gaps in understanding of atmospheric organic chemistry, hampering efforts to understand, model, and mitigate environmental problems such as aerosol formation in both polluted urban and more pristine regions. The analytical toolbox available for chemists to study atmospheric organic components has expanded considerably during the past decade, opening new windows into speciation, time resolution and detection of reactive and semivolatile compounds at low concentrations. This has provided unprecedented opportunities, but also unveiled new scientific challenges. Specific groundbreaking examples include the role of epoxides in aerosol formation especially from isoprene, the importance of highly oxidized, reactive organics in air-surface processes (whether atmosphere-biosphere exchange or aerosols), as well as the extent of interactions of anthropogenic and biogenic emissions and the resulting impact on atmospheric organic chemistry.

The successful merger of theoretical thermochemistry with fragment-based methods in quantum chemistry.

CONSPECTUS: Quantum chemistry and electronic structure theory have proven to be essential tools to the experimental chemist, in terms of both a priori predictions that pave the way for designing new experiments and rationalizing experimental observations a posteriori. Translating the well-established success of electronic structure theory in obtaining the structures and energies of small chemical systems to increasingly larger molecules is an exciting and ongoing central theme of research in quantum chemistry. However, the prohibitive computational scaling of highly accurate ab initio electronic structure methods poses a fundamental challenge to this research endeavor. This scenario necessitates an indirect fragment-based approach wherein a large molecule is divided into small fragments and is subsequently reassembled to compute its energy accurately. In our quest to further reduce the computational expense associated with the fragment-based methods and overall enhance the applicability of electronic structure methods to large molecules, we realized that the broad ideas involved in a different area, theoretical thermochemistry, are transferable to the area of fragment-based methods. This Account focuses on the effective merger of these two disparate frontiers in quantum chemistry and how new concepts inspired by theoretical thermochemistry significantly reduce the total number of electronic structure calculations needed to be performed as part of a fragment-based method without any appreciable loss of accuracy. Throughout, the generalized connectivity based hierarchy (CBH), which we developed to solve a long-standing problem in theoretical thermochemistry, serves as the linchpin in this merger. The accuracy of our method is based on two strong foundations: (a) the apt utilization of systematic and sophisticated error-canceling schemes via CBH that result in an optimal cutting scheme at any given level of fragmentation and (b) the use of a less expensive second layer of electronic structure method to recover all the missing long-range interactions in the parent large molecule. Overall, the work featured here dramatically decreases the computational expense and empowers the execution of very accurate ab initio calculations (gold-standard CCSD(T)) on large molecules and thereby facilitates sophisticated electronic structure applications to a wide range of important chemical problems.

Recent advances in heterobimetallic palladium(II)/copper(II) catalyzed domino difunctionalization of carbon-carbon multiple bonds.

The double functionalization of carbon-carbon multiple bonds in one-pot processes has emerged in recent years as a fruitful tool for the rapid synthesis of complex molecular scaffolds. This review covers the advances in domino reactions promoted by the couple palladium(ii)/copper(ii), which was proven to be an excellent catalytic system for the functionalization of substrates.

Copper catalysed Ullmann type chemistry: from mechanistic aspects to modern development.

Cu-catalysed arylation reactions devoted to the formation of C-C and C-heteroatom bonds (Ullmann-type couplings) have acquired great importance in the last decade. This review discusses the history and development of coupling reactions between aryl halides and various classes of nucleophiles, focusing mostly on the different mechanisms proposed through the years. Selected mechanistic investigations are treated more in depth than others. For example, evidence in favour or against radical mechanisms is discussed. Cu(I) and Cu(III) complexes involved in the Ullmann reaction and N/O selectivity in aminoalcohol arylation are discussed. A separate section has been dedicated to the synthesis of heterocyclic rings through intramolecular couplings. Finally, recent developments in green chemistry for these reactions, such as reactions in aqueous media and heterogeneous catalysis, have also been reviewed.

Recent advances in cholesterol chemistry.

This review article presents advances in cholesterol chemistry since 2000. Various transformations (chemical, enzymatic, electrochemical, etc.) of cholesterol are presented. A special emphasis is given to cholesterol oxidation reactions, but also substitution of the 3ß-hydroxyl group, addition to the C5-C6 double bond, C-H functionalization, and C-C bond forming reactions are discussed.

Preparation of Tyrian purple (6,6'-dibromoindigo): past and present.

Over the past century, various synthetic approaches have been suggested to the most famous dye of antiquity, Tyrian purple (6,6'-dibromoindigo). These synthetic routes have been exhaustively surveyed and critically evaluated from the perspective of convenience, cost, safety and yield.

[Investigation of biologically active compounds at the Department of Organic Chemistry of University of Debrecen between 1992-2009 part IV]. / Biológiailag aktív vegyületek kutatása a Debreceni Egyetem Szerves Kémiai Tanszékén 1992-2009 között IV. rész.

The author reviews the beginning of the application of the methods of structure elucidation by spectroscopic (metric) techniques at the Department of Organic Chemistry of University of Debrecen and summarizes the most important results obtained in this field between 1992-2009.

Future trends in microwave synthesis.

This article discusses the current status of microwave organic chemistry and briefly explains how the technology evolved to this point. Several trends in the technology and where it is likely to go in the future are also discussed. These trends include the way in which chemists think about microwave energy, the current method of use and the hardware presently available. Some of the future trends explored are microwave use in relation to materials synthesis, bioscience applications, scale up and flow chemistry.

Organic chemistry and biology: chemical biology through the eyes of collaboration.

From a scientific perspective, efforts to understand biology including what constitutes health and disease has become a chemical problem. However, chemists and biologists "see" the problems of understanding biology from different perspectives, and this has retarded progress in solving the problems especially as they relate to health and disease. This suggests that close collaboration between chemists and biologists is not only necessary but essential for progress in both the biology and chemistry that will provide solutions to the global questions of biology. This perspective has directed my scientific efforts for the past 45 years, and in this overview I provide my perspective of how the applications of synthetic chemistry, structural design, and numerous other chemical principles have intersected in my collaborations with biologists to provide new tools, new science, and new insights that were only made possible and fruitful by these collaborations.

The changing landscape of cancer drug discovery: a challenge to the medicinal chemist of tomorrow.

Since the development of the first cytotoxic agents, synthetic organic chemistry has advanced enormously. The synthetic and medicinal chemists of today are at the centre of drug development and are involved in most, if not all, processes of drug discovery. Recent decreases in government funding and reformed educational policies could, however, seriously impact on drug discovery initiatives worldwide. Not only could these changes result in fewer scientific breakthroughs, but they could also negatively affect the training of our next generation of medicinal chemists.

Diversity-oriented synthesis.

Diversity-oriented synthesis (DOS), which describes the synthesis of structurally diverse collections of small molecules, was developed, in part, to address combinatorial chemistry's shortfalls. In this paper, we hope to give an indication of what can be achieved using the DOS approach to library generation. We describe some of the most successful strategies utilized in DOS, with special focus on our own area of interest; DOS from simple, pluripotent starting materials.