Microbial and Enzymatic Processes for the Production of Biologically and Chemically Useful Compounds [New Synthetic Methods (69)

Heterocyclic compounds are an important class of compounds in the field of pharmaceutical and synthetic organic chemistry. The Schiff bases contain azomethine linkages which are obtained by the condensation of aldehyde/ketone with amines. Among the various types of Schiff bases, the chalcone-based Schiff bases play a vital role in the treatment of various ailments and various applications, which can be synthesized by using different types of chalcones as the starting materials. These types of compounds were synthesized by using various techniques like conventional means of synthesis, microwave-assisted reaction, heterocyclic catalyst-mediated synthesis and also by means of trituration. The chalcone or bis-chalcone-based Schiff bases and their derivatives contain -C=N linkage which exhibits various activities including antimicrobial, anticancer, antioxidant, antidiabetic and immunosuppressant activities. Beyond these activities, these types of Schiff bases are also used in various chemical industries and fluorescent sensors, which also play a major role in the field of synthetic organic chemistry and coordination chemistry as intermediates. This review discusses the numerous synthetic strategies along with their applications in the field of medicine. Thus, this review will be helpful in developing more effective drug-like scaffolds for use in future drug design. Keywords: Schiff bases, Chalcone-based Schiff bases, Antimicrobial, Anticancer, Antioxidant, Biological Applications

In the periodic table of elements, indium is located within group 13, and has the atomic number 49. Indium is classified as one of the chemical elements of post-transition metals. Indium is silvery-white in color, soft, and possesses a high level of malleability. Although indium is a relatively rare element, it is indispensable in industry applications worldwide. German metallurgists discovered indium in 1863. It was not until the early 1990s, however, that scientists in the field of synthetic organic chemistry attempted genuine studies to explore the roles of indium or indium-related reagents. Focusing on indium or indium-related reagents, many recent investigations have led to significant advances in synthetic organic chemistry. Various applications have been examined and a growing number of useful chemical transformations using indium or indium-related reagents are being revealed and reported. Chemical transformations of the reactive functional groups are an essential point, particularly for the successful implementation of a sequence of multiple-step chemical schemes. For this purpose, a variety of strategic reaction methodologies have been developed, including those utilizing indium or indium-related reagents. Indium metal was discovered to be useful for the protection and deprotection of functional groups, while trivalent indium Lewis acids have been effective in a wide variety of chemical transformations. This chapter describes an efficient oxone-mediated esterification of aldehydes using indium(III) triflate, which is also one of the trivalent indium Lewis acids. Esterification is performed primarily on aromatic and heterocyclic aldehydes. The results show the effectiveness of this esterification methodology and suggest the potential in the further development of these reagents, which could enhance the field of synthetic organic chemistry.

Dendrimers are a new class of macromolecule increasingly used in the fields of synthetic organic chemistry, biology, medicine and biotechnology. Dendrimers in Medicine and Biotechnology: New Molecular Tools looks at this exciting and rapidly growing area of science. Using an interdisciplinary approach with particular emphasis on biological applications, the book discusses the relationship between the dendrimer molecular motif and its biological properties. A general introduction to the subject of dendrimers, including definitions of terms and symbols, is provided. Subsequent sections discuss topics including dendrimers in biological systems, dendrimers as drug delivery devices, dendrimers in diagnostics and dendrimer drugs. Throughout the book examples from current research are also provided. This book will appeal to a wide range of scientists, including non specialists who require an introduction to dendrimers, as well as those wishing to know more about the application of dendrimers in the field of biology and medicine.

In the field of synthetic organic chemistry, photochemical and electrochemical approaches are often considered to be competing technologies that induce single electron transfer (SET). Recently, their fusion, i. e., the "photoelectrochemical" approach, has become the focus of attention. In this approach, both solar and electrical energy are used in creative combinations. Historically, the term "photoelectrochemistry" has been used in more inorganic fields, where a photovoltaic effect exhibited by semiconducting materials is employed. Semiconductors have also been studied intensively as photocatalysts; however, they recently have taken a back seat to molecular photocatalysts. In this account, we would like to revisit semiconductor photocatalysts in the field of synthetic organic chemistry to demonstrate that semiconductor "photoelectrochemical" approaches are more than mere alternatives to molecular photochemical and/or electrochemical approaches.

Recently, electron has been recognized as the simplest catalyst in the field of synthetic organic chemistry. Addition or removal of electron can activate small molecules for further chemical transformations, which is referred to as redox catalysis. Reductive and/or oxidative single electron transfer (SET) can be induced by means of electro- and photochemistry, where an electron can play a role of catalysts. Radical ions are primarily generated via SET, offering unique reactive intermediates.Distonic radical ions are transient species with formally separated radical and charge cites. They potentially exhibit radical and ion reactivities independently, which may differ from usual radical ions. However, distonic radical ions are not commonly used as reactive intermediates in the field of synthetic organic chemistry, probably because of lack of their simple generation methods.We have been developing oxidative SET-triggered cycloadditions in a lithium perchlorate/nitromethane solution. Radical cations are involved in the reactions as distinctive reactive intermediates, facilitating intermolecular carbon-carbon bond formations. We questioned whether the distonic radical cation can also be generated by oxidative SET, leading to novel chemical transformations. In this presentation, oxidative SET-catalyzed vinylcyclopopane rearrangements will be described. Figure 1

17 - Applications of the Olefin Metathesis Reaction

Explosive growth in the use of open shell reactivity, including neutral radicals and radical ions, in the field of synthetic organic chemistry has been observed in the past decade, particularly since the advent of ruthenium complexes in 2008. These complexes generally induce single-electron transfer (SET) processes via visible-light absorption. Additionally, recent significant advancements in organic electrochemistry involving SET processes to provide open shell reactivity offer a complementary method to traditional polarity-driven reactions described by two-electron transfer processes. In this Review, we highlight the importance of intramolecular SET processes in the field of synthetic organic chemistry, which seem to be more elusive than the intermolecular versions, since they are net redox-neutral and thus cannot simply be regarded as oxidations or reductions. Such intramolecular SET processes can rationally be understood in combination with concomitant bond formations and/or cleavages, and are regulated by a structural motif that we call a "redox tag." In order to describe modern radical-driven reactions involving SET processes, we focus on a classical formalism in which electrons are treated as particles rather than waves, which offers a practical yet powerful approach to explain and/or predict synthetic outcomes.

ConspectusThe selective functionalization/transformation of ubiquitous pyridine-fused N-heteroarenes is a practical method to synthesize structurally novel N-heterocycles, which is important for the development of medicines, bioactive agents, agrochemicals, materials, ligands, sensors, pigments, dyes, etc. However, owing to thermodynamic stability, kinetic inertness, and lone electron pair-induced catalyst deactivation of the pyridine-fused N-heteroarenes, limited strategies (e.g., C-H activation/functionalization, electrophilic substitution, and the Minisci reaction) are available to realize the synthetic purpose and maintain the aromaticity of the final products. Moreover, the relevant transformations have limitations such as needing harsh reaction conditions, requiring the preinstallation of specific coupling agents containing transformable functionalities or directing groups, using less environmentally benign oxidants and/or acidic activators, and poor selectivity. Herein, considering that imines, enamines, radicals, and cyclic amines are generated during the reduction of pyridine-fused N-heteroarenes, the precise transformation of these reductive intermediates offers a fundamental basis for developing novel tandem reactions. Our group revealed that a slow reduction rate, synergistic catalysis, and controlled electroreduction are effective strategies for fulfilling the selective reductive functionalization of pyridine-fused N-heteroarenes. Thus, we established a series of new synthetic methods that provide diverse construction modalities for functionalized N-heterocycles. The striking features of these synthetic methods include high efficiency, atom economy, and the use of readily accessible N-heteroarenes as transformable feedstocks in the absence of flammable and pressurized H2 gas, alongside a promising potential of the obtained N-heterocyclic products. The present study would be appealing to the fields of synthetic organic chemistry, catalysis, biomedical chemistry, and functional materials. This Account describes the application of reductive dearomatization as substrate-activating and tandem reaction-initiating modes and summarizes the reductive functionalization of pyridine-fused N-heteroarenes via selective alkylation, arylation, and annulation at nitrogen, α, β, and other remote carbon sites achieved over the past 8 years. Details regarding the development of new reactions and their plausible mechanisms and perspectives are discussed. We hope our contributions to this field will aid in the further development of novel strategies for the functionalization/transformation of pyridine-fused N-heteroarenes and tackle the intractable challenges in this area.

Abstract3,4‐Fused tricyclic indole frameworks are found in various bioactive natural products and pharmaceuticals. The development of an efficient synthetic method for this structural motif has therefore attracted attention in the field of synthetic organic chemistry and medicinal chemistry. Herein, we summarize recent advances in the synthesis of 3,4‐fused tricyclic indoles. This class of synthetic methods can be roughly classified into two categories: methods using functionalized indole derivatives as starting materials to construct a fused medium‐sized ring (Types A–D: Category I), and methods of constructing a 3,4‐fused tricyclic indole skeleton via indole ring formation (Types E–G: Category II). In this focus review, synthetic methods for 3,4‐fused tricyclic indoles classified as Category II methods are highlighted, following a brief overview of the Category I methods.

Enzymes, at the turn of the 21st century, are gaining a momentum. Especially in the field of synthetic organic chemistry, a broad variety of biocatalysts are being applied in an increasing number of processes running at up to industrial scale. In addition to the advantages of employing enzymes under environmentally friendly reaction conditions, synthetic chemists are recognizing the value of enzymes connected to the exquisite selectivity of these natural (or engineered) catalysts. The use of hydrolases in enantioselective protocols paved the way to the application of enzymes in asymmetric synthesis, in particular in the context of biocatalytic (dynamic) kinetic resolutions. After two decades of impressive development, the field is now mature to propose a panel of catalytically diverse enzymes for (i) stereoselective reactions with prochiral compounds, such as double bond reduction and bond forming reactions, (ii) formal enantioselective replacement of one of two enantiotopic groups of prochiral substrates, as well as (iii) atroposelective reactions with noncentrally chiral compounds. In this review, the major enzymatic strategies broadly applicable in the asymmetric synthesis of optically pure chiral compounds are presented, with a focus on the reactions developed within the past decade.

Steroids have revolutionized modern-day medicine, aiding in the treatment of a broad range of diseases, including arthritis, lupus, and multiple sclerosis. The pioneering research on steroids at the Upjohn Company was honored with a National Historic Chemical Landmark during a May 17 ceremony at the Kalamazoo Valley Museum in Kalamazoo, Michigan, where Upjohn was founded in 1886. "Many of these modern drug therapies would not be available today without the pioneering research and development that occurred at Upjohn over an incredible 60-year period starting in 1930," says American Chemical Society immediate past president Peter Dorhout. "The medicinal chemistry innovations, microbial and chemical transformation discoveries, and manufacturing processes developed by Upjohn for its steroid medicine program transformed not only the pharmaceutical industry but also the entire field of synthetic organic chemistry." In 1935, Upjohn became the first company to market an adrenocortical steroid product, and by the late 1940s, the company

In the field of synthetic organic chemistry, the dehalogenations are common and interesting reactions. Typical procedures generally use electrochemical, photochemical, and ultrasonic techniques. Within the broad range of conditions for carrying out such reactions, the use of indium is of particular interest because it can be utilized in different solvents as organic media, water or without solvent. Besides, this metal is stable in air and its toxicity is lower compared with to that observed in other metals.1,2 In the context of contributing to the development of new synthetic methodology in the field of indium chemistry, as a preliminary study, we propose the use of ionic liquid as alternative solvent to carry out dehalogenation reactions. Dehalogenation of aromatics compounds was investigated by a series of reactions under several conditions. Bromobenzene was used as a starting material and due to ionic liquids (IL) have well-known properties as green solvents, we tested this procedure changing the IL.3,4 The treatment of bromobenzene with [bmim]Cl and [bmim]Br afforded the corresponding dehalogenated derivative in good to excellent yield. However, when using as an alternative others ionic liquids [bmim]PF6, [bmim]BF4, [bmpy]F3CSO3 and TBAF, reactions did not proceed. In order to ensure the validity of the results shown above for bromobenzene, we proceeded to extend this method for chlorinated and iodinated benzene. Our experimental results indicate that [bmim]Br is the most effective solvent for this reaction. To explore the scope of this dehalogenation reaction, we investigated the behavior of others haloaromatics and haloheteroaromatics systems using indium under [bmim]Br conditions. The yields of dehalogenated products were in moderate to excellent range. In conclusion, we have demonstrated that a reductive system consisting of an indium powder in ionic liquid allows a highly conversion of haloaromatics and haloheteroaromatics compounds. This work was supported by Bicentenario Project PSD-70, Interdisciplinary Project 27/2011, and Research Project 3901-026-81, Chemistry Faculty, Pontificia Universidad Católica de Chile. References 1 Alonso, F.; Beletskaya, I.; Yus, M. Chem. Rev. 2002, 102, 4009-4091. 2 Ranu, B. C.; Dutta, P.; Sarkar, A. J. Chem. Soc., Perkin Trans. I, 1999, 1139-1140. 3 Pavlinac, J.; Zupan, M.; Laali, K.; Stavber, S. Tetrahedron, 2009, 65, 5625-5662. 4 Sowmiah, S.; Srinivasadesikan, V.; Tseng, M-C.; Chu, Y-H. Molecules, 2009, 14, 3780-3813.

Ionic liquids are used in various fields due to their unique physical properties and are widely utilized as reaction solvents in the field of synthetic organic chemistry. We have previously proposed a new organic synthetic method in which the catalyst and reaction reagents are supported on ionic liquids. This method has various advantages, such as the ability to reuse the reaction solvent and catalyst and its facile post-reaction treatment. In this paper, we describe the synthesis of an ionic liquid-supported anthraquinone photocatalyst and the synthesis of benzoic acid derivatives using this system. This synthesis of benzoic acid derivatives via the cleavage of vicinal diols by an ionic liquid-supported anthraquinone photocatalyst is an environmentally friendly process, and furthermore, it has a simple post-reaction process, and the catalyst and solvent can both be reused. To the best of our knowledge, this is the first report on the synthesis of benzoic-acid derivatives via the cleavage of vicinal diols using light and an ionic-liquid-supported catalyst.

Azanucleosides are found to show unique pharmacological activities even without incorporating into oligonucleotides and are used as anticancer and antivirus agents. Practical synthesis routes of azanucleosides are of exceptional importance to enhance the development of (oligo)nucleotide therapeutics. Previously, we reported the synthetic methods of azanucleosides by using electrochemical approaches, which has now been offering green and sustainable redox options in the field of synthetic organic chemistry. However, scaling-up of the reactions remains challenging since continuous production is essentially not possible. Herein, we report the direct anodic N-α hydroxylation of prolinol derivatives as useful intermediates for azanucleosides. Cyclic voltammetry study clearly reveals that the presence of water facilitates the oxidative electron transfer events. The reaction is applicable for large scale production and thus could enhance the development of (oligo)azanucleotide therapeutics.

This review describes the latest synthetic methods found in the literature for the construction of complex natural products containing the spiro[pyrrolidine-3,3′-oxindole] ring system and other oxindoles that are closely related. The spirooxindole system is the central structure of many different types of natural products and synthetic drugs, which are associated with various biological activities. The well-known interest that these compounds inspire in academia, as well as in industry together with our efforts toward the total synthesis of sarpagine-/macroline-related oxindoles inspired us to review this topic. Herein, the strategies used by other expert groups in the field of synthetic organic chemistry and their results are presented in a critical way. The examples were selected on the basis of the elegant way chemists resolved their synthetic challenges. Many other excellent syntheses of complex oxindoles can be found in the literature, but were not included due to the limit in the length of this manuscript.