meso Compounds: Stepchildren or Favored Children of Stereoselective Synthesis?

After more than a quarter of a century of development, the methodology of stereoselective synthesis appears to be fully matured. In line with this, the potential that meso compounds offer in stereoselective synthesis is clearly recognized. The use of meso compounds in synthesis is, however, in no way commensurate with this potential, because, ironically, the synthesis of meso compounds in the first place is a problem of stereoselective synthesis. Present-day methodology does not provide many useful solutions to this problem. This Review therefore addresses the strategies available for the synthesis of more elaborate meso compounds whose stereogenic centers have a distance >1,4 between them. meso Compounds with more than four stereogenic centers are also considered. The criteria used in choosing from several strategies in the synthesis of such compounds are discussed.     

Hydrotalcite catalysis for the synthesis of new chiral building blocks

The use of hydrotalcites for the synthesis of two chiral building blocks in a simple way is described as a new and green methodology. The synthesis of these compounds implies a regioselective Baeyer–Villiger reaction in a very selective way with ulterior opening and lactonisation. This methodology should be considered green for the use of hydrogen peroxide as the only oxidant and hydrotalcites as the catalyst, and because no residues are produced apart from water. The procedure is very adequate for using in gram scale, in order to increase the value of the obtained compounds. The conditions are excellent and can be applied for nonstable compounds, as they are very mild. The synthesised compounds are magnific starting materials for the synthesis of biologically active or natural compounds. The use of a cheap, commercial and chiral compound as carvone disposable in both enantiomeric forms adds an extra value to this methodology.     

Toward high-throughput synthesis of complex natural product-like compounds in the genomics and proteomics age

In the age of high-throughput biology, novel genes and proteins are emerging quickly. The need for developing organic synthesis-derived methods that allow rapid access to polyfunctional, complex natural product-like compounds is growing constantly, largely because these small-molecule-based compounds serve as smart, powerful tools both in understanding the roles and functions of emerging biological targets and in validating their biological responses. Developing asymmetric synthesis-derived organic reactions on solid phase allows the synthesis of complex natural product-like compounds in a high-throughput manner. Solid phase organic synthesis is now commonly utilized in the library synthesis of rather simple compounds (i.e., compounds with no multiple stereogenic centers). With few exceptions, the synthesis of complex natural product-like derivatives is still in its infancy. Some recent efforts made in this area indicate opportunities yet to be explored.     

Synthesis,Chemistry and Applications of Heterocyclic Cage Compounds (V)

The synthesis and chemistry of polycyclic cage compounds have attracted considerable attention in recent years.¹ The vast majority of the work reported in this area has dealt with caybocyclic cage compounds. On the other hand, the synthesis and chemistry of heterocyclic cage compounds have received less attention. Recently, we have accomplished the synthesis of a series of oxa-cage compounds and performed the chemical transformations of these oxa-cage compounds.² As part of a program that involves the synthesis,chemistry and applications of heterocyclic cage compounds we report here the synthesis of heterocyclic cage compounds 1-12. We also wish to report the applications of compounds 7-12 on the π-facial selectivities. Studies on the cation-binding properties of compounds 1 and 2 and other oxa-cages are undertaken.     

Influence of dipole moments on the medicinal activities of diverse organic compounds

In this study, synthesis, biological activity and structure-activity relationships of diverse compounds are described. In general, the relationships between dipole moment and biological activities are discussed in detail. Despite progress of interdisciplinary science, the use of dipole moment values of organic compounds to understand their potent medicinal activities in various diseases remains unexplored. In contrast, it can be seen that many compounds demonstrate a direct correlation between biological activity and dipole moment. Therefore, analyzing the dipole moment values, scientists may design more potent compounds prior to their synthesis which is tedious, costly and time-consuming.     

1,3-Cyclohexadien-1-Als: Synthesis,Reactivity and Bioactivities

In synthetic organic chemistry, there are very useful basic compounds known as building blocks. One of the main reactions wherein they are applied for the synthesis of complex molecules is the Diels–Alder cycloaddition. This reaction is between a diene and a dienophile. Among the most important dienes are the cyclic dienes, as they facilitate the reaction. This review considers the synthesis and reactivity of one of these dienes with special characteristics—it is cyclic and has an electron withdrawing group. This building block has been used for the synthesis of biologically active compounds and is present in natural compounds with interesting properties.     

Diels-Alder Reactions of 6-Hydroxy-2H-pyran-3(6H)-ones with Cyclopentadiene and Its Application for the Synthesis of New Skeletal Oxa-Cage Compounds

The 2(5H)-furanone and 3(6H)-pyranone structures are frequently found in natural products, which have a broad range of biological activities. In addition, furanones and pyranones have served as versatile intermediates in the synthesis of a variety of products. 1 Recently, we envisioned that studies on the synthesis and chemistry of heterocyclic cage compounds can greatly expand the scopes and utilities of cage compounds.2 As part of a program that involves the synthesis, chemistry, and applications of heterocyclic cage compounds, we report here the Diels-Alder reactions of 6-hydroxy2H-pyran-3(6H)-ones 1 and 2 with cyclopentadiene and the application of the cycloadducts for the synthesis of oxa-cage compounds 3-6 with new skeleton. Compound 6 is a potential new chiral amino-alcohol.     

Ultrasound irradiation in heterocycle synthesis: An overview

The synthesis of heterocyclic compounds has been a hot topic for several decades. Synthetic organic chemists are always in search of new methodologies which are greener for the synthesis of heterocyclic compounds. The ultrasound-assisted reactions have contributed much to this field. This review focuses on the impact of sonochemistry in the synthesis of heterocyclic compounds and covers the literature from 2009 to 2020.     

A New Route for the Synthesis of 1,4-Dicarbonyl Compounds: Synthesis of Jasmone,Dlhydrojasmone and a Prostaglandin Intermediate

1,4-Dicarbonyl compounds are versatile intermediates for the synthesis of a variety of natural products such as jasmonoids, prostanoids, steroids and terpenoids having a cyclopentenone or furan ring system. Although many synthetic routes for the preparation of these compounds are known and continue to appear¹, most of the existing methods involve lengthy procedures and are limited to the synthesis of 1,4-diketones. Herein, we report a convenient three step approach for the synthesis of 1,4-dicarbonyl compounds starting from tosyl methyl isocyanide² (TosMIC). This method is general for the preparation of 1,4-ketoaldehydes as well as 1,4-diketones.     

Synthesis of Metastable Inorganic Solids with Extended Structures

The number of known inorganic compounds is dramatically less than predicted due to synthetic challenges, which often constrains products to only the thermodynamically most stable compounds. Consequently, a mechanism-based approach to inorganic solids with designed structures is the holy grail of solid state synthesis. This article discusses a number of synthetic approaches using the concept of an energy landscape, which describes the complex relationship between the energy of different atomic configurations as a function of a variety of parameters such as initial structure, temperature, pressure, and composition. Nucleation limited synthesis approaches with high diffusion rates are contrasted with diffusion limited synthesis approaches. One challenge to the synthesis of new compounds is the inability to accurately predict what structures might be local free energy minima in the free energy landscape. Approaches to this challenge include predicting potentially stable compounds thorough the use of structural homologies and/or theoretical calculations. A second challenge to the synthesis of metastable inorganic solids is developing approaches to move across the energy landscape to a desired local free energy minimum while avoiding deeper free energy minima, such as stable binary compounds, as reaction intermediates. An approach using amorphous intermediates is presented, where local composition can be used to prepare metastable compounds. Designed nanoarchitecture built into a precursor can be preserved at low reaction temperatures and used to direct the reaction to specific structural homologs.     

Ferrocene modification of organic compounds for medicinal applications

The results of the authors on the synthesis of ferrocene-containing organic compounds obtained in 1998–2013 are summarized. The review is focused on the ferrocene modifications of purine and pyrimidine bases, thiopyrimidines, natural and synthetic amino acids, azoles (including polyfluoroazoles and mercaptoazoles) and ferrocenyl quinoline synthesis. The special attention is given to the scale synthesis of compounds for biological trials.     

Phase transfer catalyzed aziridination of α-bromo-2-cyclopenten-1-one

An efficient and highly selective synthesis of bicyclic-α-keto aziridines from 2-bromo-2-cyclopentenone and aliphatic primary amines mediated by phase transfer catalysts (PTCs) in water at room temperature is demonstrated. Bicyclic-α-keto-aziridines are highly strained and reactive compounds that can be used in the synthesis of biologically active compounds. Therefore, the present strategy with its mild reaction conditions opens up a new entry to the synthesis of unusual aziridines using inexpensive reagents.     

Biological potential of pyrimidine derivatives in a new era

Pyrimidine and its derivatives play a wide role in drug discovery processes and have considerable chemical significance and biological activities. Pyrimidines are the building blocks of many natural compounds such as vitamins, liposacharides, and antibiotics. Pyrimidine is used as parent substance for the synthesis of a wide variety of heterocyclic compounds and raw material for drug synthesis and is also crucial in the theoretical development of heterocyclic chemistry and in organic synthesis. Pyrimidine derivatives are vital in several biological activities, i.e. antihypertensive, anticancer, antimicrobial, anti-inflammatory, and antioxidant activity. This creates interest among researchers who have synthesized a variety of pyrimidine derivatives.     

Synthesis of symmetrical biaryl compounds by homocoupling reaction

Since the development of the Ullmann coupling in the early 20th Century, there has been intense and continuous research on the syntheses of biaryl compounds, which appears as an interesting branch of organic chemistry.A myriad of methodologies for the synthesis of biaryl compounds have been studied and well established, including homocoupling methodologies, which in general are robust as well as consolidated strategies. Biaryl systems are quite relevant building blocks for the synthesis of more complex chemical structures. Besides the diversity of functional groups that can be used to promote a new aryl-aryl bond, there is a wide variety of transition metals that can act as catalyst in these processes.In this review, we summarized numerous methodologies of homocoupling reactions for the synthesis of symmetrical biaryl compounds.     

Synthetic and biological studies of pyrazolines and related heterocyclic compounds

This review provides a comprehensive survey relating to the synthesis and biological applications of pyrazolines and related heterocycles in the last five years (2007–2011). These compounds are usually prepared from the cyclization of chalcones with hydrazine and its derivatives under the alcoholic conditions. The major incentive behind the synthesis of these compounds was the immense biological activities associated to these heterocyclic derivatives. The aim of this review is to find out different methods for the synthesis of pyrazoline derivatives.     

First total synthesis of a natural product containing a chiral,beta-diketone: synthesis and stereochemical reassignment of siphonarienedione and siphonarienolone

The first total syntheses of siphonarienolone and siphonarienedione are described. The development of a stereoselective synthesis of beta-diketones facilitated the synthesis of the latter compound. The synthesis of the structures proposed for the natural products afforded compounds whose spectral data did not match those of the natural products. However, the synthesis of compounds isomeric to the proposed structures at C(4) and C(5) afforded compounds identical to the natural products, thereby reassigning the stereochemistry of the natural products.     

Split--pool synthesis of 1,3-dioxanes leading to arrayed stock solutions of single compounds sufficient for multiple phenotypic and protein-binding assays.

Diversity-oriented organic synthesis offers the promise of advancing chemical genetics, where small molecules are used to explore biology. While the split--pool synthetic method is theoretically the most effective approach for the production of large collections of small molecules, it has not been widely adopted due to numerous technical and analytical hurdles. We have developed a split--pool synthesis leading to an array of stock solutions of single 1,3-dioxanes. The quantities of compounds are sufficient for hundreds of phenotypic and protein-binding assays. The average concentration of these stock solutions derived from a single synthesis bead was determined to be 5.4 mM in 5 microL of DMSO. A mass spectrometric strategy to identify the structure of molecules from a split--pool synthesis was shown to be highly accurate. Individual members of the 1,3-dioxane library have activity in a variety of phenotypic and protein-binding assays. The procedure developed in this study allows many assays to be performed with compounds derived from individual synthesis beads. The synthetic compounds identified in these assays should serve as useful probes of cellular and organismal processes.     

Advances in the field of organo-element polymers

Organo-element polymers are a rapidly developing field of high molecular weight compounds. As A.N. Nesmeyanov points out, the organo-element polymer chemistry is the science lying between inorganic and organic chemistry, that is undoubtedly its positive factor, because this allows to prepare polymeric compounds combining positive properties of the compounds of these two fields. Due to this, many elements of the Periodic System capable of forming various polymeric compounds are widely investigated, and a number of organo-element polymers have already found practical application in many fields of modern engineering and national economy. It should be noted that at present already more than 75 elements have been used in synthesis of various high molecular weight organo-element compounds. Besides carbon, among these compounds hydrogen, oxygen and silicon are remarkable. Other elements only begin their way to the polymer field. The concept of raznozvennost (different-units structure) is of great importance for studying the synthesis and the properties of these polymers. This concept made it possible to clarify distinguishing role of anomalous units in determining the complex of physico-chemical properties of high molecular weight organo-element compounds. It is especially important to emphasize that among factors giving rise to anomalous units causing polymer raznozvennost the presence of stable isotope atoms arranged statistically in polymer macromolecules plays an essential role. The lecture is a general review of polymers by the groups of the Periodic System. It discusses the methods for synthesis of organo-element polymers used at the present time as well as perspective development of this field in the future.     

A review on synthetic approaches of heterocycles via insertion-cyclization reaction

Abstract

Heterocyclic compounds have a wide range of applications: they are predominant among the type of compounds used as pharmaceuticals, agrochemicals, fine chemicals, electronic components, polymers, and veterinary products. There is a vast scope to develop new heterocyclic compounds considering the high yield, low waste, and green synthesis. In this review, we have described the synthesis of heterocycles via insertion and cyclization which is achieved in recent years with the ideas, challenges, and milestone reactions.     

Cascade polycyclization: exploration of a convergent route to access various tricyclic and tetracyclic products related to sterols

The expedient synthesis of tricyclic and tetracyclic compounds via a cascade polycyclization methodology is described. Nazarov substrates (II) containing two Michael acceptors and a cyclohexenone ester (I) underwent cycloaddition followed by intramolecular 1,4-addition to furnish, in a highly stereoselective manner, tricyclic and tetracyclic products (III). Such compounds are interesting intermediates for the synthesis of polycyclic natural and unnatural products.