Current Organic Synthesis - Volume 12, Issue 5, 2015

This review deals with the important changes that have taken place in the last twenty to thirty years, on the directions and objectives of organic synthesis. Target oriented synthesis now competes with diversity oriented synthesis, and variations, in an attempt to occupy chemical space more completely. At the same time practicality, efficiency, scalability and robustness are once again the major goals to be associated with atom, step and function economies, within the context of sustainability.

Cryptomoscatones D1 and D2, dihydropyranones isolated from C. mandiocanna, had their stereochemistry solved after total syntheses and comparison of spectroscopic data of natural and synthetic samples. Natural dihydropyranones coibacins A and B, metabolites isolated from marine cyanobacterium cf. Oscillatoria sp, which display antileishmanial activity and anti-inflammatory properties, were synthesized and had their absolute configuration determined. Our efforts towards the synthesis of cryptomoscatone E3, natural dihydropyranone with unknown absolute configuration, are also discussed.

This article gives a historical background on the introduction of the chalcogen chemistry in Brazil. It also describes the development of synthetic methods based on organotellurium compounds, and their use in the synthesis of biologically active compounds. A brief comment on the biological activity of organotellurium compounds is also made.

Carbonyl chemistry, specifically aldol reactions, is one of the most efficient and elegant strategies to build carbon-carbon bonds. In the last 15 years in Brazil, our research group and others have worked on the development and application of stereoselective aldol reactions, with direct application in the asymmetric synthesis of several natural products of biological interest. In this review, we highlight the major Brazilian contributions to this field.

We report herein a straightforward and efficient route to prepare 1H-1,2,3-triazoles-linked to 2,3- dihydronaphtho[1,2-b]furan-4,5-dione in C-2 in a one-step reaction from readily available starting materials. We performed a one-step procedure from iodocyclization of 3-allyl-lawsone followed by a nucleophilic substitution reaction of the iodized product, and finally the Huisgen 1,3-dipolar cycloaddition reaction catalyzed by Cu(I) provide 1H-1,2,3-triazol-1-ylmethyl-2,3-dihydronaphtho[1,2-b]furan-4,5-diones.

Niobium is not found in nature in its free form, but usually in the form of oxides and usually with the tantalum element. The largest niobium reserves are in Brazil. The use of niobium compounds in organic synthesis has increasingly attracted the attention of the international scientific community due to its wide range of applications. Among all the applications, we highlight heterogeneous catalysis. The compounds most widely studied in recent years are on niobium pentachloride, acting as a strong Lewis acid, and niobium pentoxide, acting as an acid catalyst or even as a support for other catalysts. In this review, we will discuss several studies over the last three years in organic chemistry using niobium pentachloride, niobium pentoxide, and other niobium compounds.

D-Ribonolactone is a carbohydrate derivative of the aldonolactone family which serves as a versatile chiral pool for the total synthesis of natural products such as malayamycin, varitriol, mannostatin, shikimic acid, herbarumins, neplanocins, and many others. Also, the preparation of new C-nucleosides starting from D-ribonolactone has attracted the attention of several groups in the past decade, since this class of molecules is much less amenable to enzymatic and acid-catalyzed hydrolysis than natural and synthetic N-nucleosides. In addition, the extension of the genetic alphabet could produce new combinations of three-letter codons, potentially generating proteins containing nonbiogenic amino acids, resulting in non-natural properties. This review addresses recent methodologies (published in the past two decades) for the preparation of D-ribonolactone and its analogues, as well as their use as building blocks for the synthesis of naturally occurring compounds and biologically relevant entities in the fields of medicinal chemistry and chemical biology.

Haloarenes are important chemical compounds from academic, biological, and industrial point of view. They can usually be prepared by an electrophilic halogenation of aromatic compounds using the halogen in its elemental form (X2), a reaction formerly described by Couper in 1857. Recently, the interest in new reagents that can accomplish a safe, efficient, and convenient halogenation of arenes has grown enormously. The present review summarizes the utilization of trihaloisocyanuric acids in the electrophilic aromatic halogenations and focuses on their green aspects.

Phenolic lipids constitute a class of bioactive compounds comprising molecules having hydrophobic tails linked to a phenolic polar head, widely distributed in nature, with great variety of biological and industrial potential. The cytosporones, which are octaketide phenolic lipids, have been attracting the attention of many researchers owing to their biological potential, such as fungicidal, allelopathic, bactericidal and, cytotoxic activities. In 2008, it was noticed that the so-called cytosporone B specifically binds to the ligand-binding domain of Nur77 or TR3, and is a potent killer in agonist stimuli. Some research groups are constantly striving to synthesize cytosporones and, many works have been published since 2003. Recently, some new similar octaketides were isolated and a few synthetic approaches are reported in the literature. Many results point out that cytosporones are potential molecules to develop promising pharmaceutical and agrochemical agents.

Hepatitis C is a life threatening viral disease that commits millions of people worldwide. During the last decades, important developments in the understanding of the structural biology and biochemistry of the virus led to the development of direct acting antivirals culminating in the breakthrough development of the NS5B pronucleotide inhibitor Sofosbuvir which was approved by the FDA in 2013 to treat hepatits C. The advent of directing acting antivirals increased the sustained antiviral response from 38%-44% with peguilated interferon and ribavirin to 90-95% depending on the genotype. The path that led to Sofosbuvir passes through the development of important nucleosides such as 2`C-metil nucleosides and 2’-Me-2`F-2`-desoxi-nucleosides some of which achieved phase II clinical trials. The present work intends to review the developed chemistry that culminated in the abovementioned nucleosides as well as the chemistry of their pro-nucleotides phosphoramidates.

Insertion of diazocarbonyl-derived metallocarbenes into X-H bonds (X= H, C, Si, N, O, S, P, Se) has proven to be a very important method for the construction of C-X bonds in organic chemistry. This mini-review provides a brief historical background, mechanistic aspects and a summary of recent breakthroughs in the area of enantioselective metal-catalyzed N-H and O-H insertion reactions.

A new class of modular functionalized oxazolines are synthesized using a simple, novel one-pot method under inert moisture-free conditions. Then the oxazolines can be further elaborated to phosphine-containing oxazolines. The first step is to synthesize intermediates via the reaction of 2 - hydroxybenzonitrile or 2- aminobenzonitrile with chiral amino alcohols, subsequent reactions with phosphine chlorides, providing products in moderate yields. Product structures are fully characterized by NMR, IR, MS and X-Ray analyses. These compounds are found to be highly active catalysts for the cyanosilylation of prochiral benzaldehyde (20-96% yield).