Current Organic Chemistry - Volume 18, Issue 16, 2014

Heterocycles are fundamental building blocks for natural products and biologically active compounds. Over the past decades, substantial progress has been made in transition metal-catalyzed C-H bond functionalization. The majority of C-H functionalization studies have been focused on the formation of C-C bond, and the synthesis of heterocyclic compounds has been generally achieved from further elaboration of the resulting products after C-H functionalization. However, in very recent years, direct C-heteroatom coupling via C-H functionalization followed by C-heteroatom (heteroatom = N, O, S, P, etc.) bond formation has been extensively developed, providing efficient protocols for synthesizing various heterocycles. In this review, a brief overview is given of the recent advances in the field. The synthetic strategies are categorized and presented according to (1) types of C-H bonds (Csp2-H and Csp3-H) and (2) types of Cheteroatom bonds formed.

Substituted purine nucleosides and nucleotides are considered as indispensible diagnostic tools since they find different applications in molecular genetics and next generation nucleic acid sequencing. This class of molecules also has pharmaceutical and other biological significance. Both carbon and nitrogen can be used as anchoring points for attaching various kinds of functional labels such as dyes and binding molecules. For carbon substituted nucleosides and nucleotides, C-6 is the most widely used anchoring point. Besides, C-2 and C-8 have also been used as anchoring points. For nitrogen substituted nucleosides and nucleotides, N-1, N-2, N-6, N-7 have demonstrated their abilities for anchoring different labels. This review will mainly focus on C-6 substituted nucleosides and nucleotides, followed by a brief summary of other substituted nucleosides and nucleotides. The past few decades have witnessed the tremendous progress in the chemical synthesis and manufacture of these substituted purine nucleosides and nucleotides. Different strategies such as halogenation, lithiation, nucleophilic substitution, nucleophilic aromatic substitution, transition metal catalyzed cross-coupling, alkylation, 1, 3-dipolar cycloaddition, nickel catalyzed cyclotrimerization and click chemistry have greatly accelerated this process. The main goal of this review is to summarize the available strategies in literature to synthesize substituted purine nucleosides and nucleotides and to keep the nucleic acid chemistry community updated with the most recent progress in this field.

The indole network has been identified as an important pharmacophore of several natural products and synthetically prepared molecules. Asymmetric organocatalytic Friedel-Crafts alkylations of electron rich indoles are of enormous significance for the synthesis of many bioactive compounds, natural products and anti-cancer drugs. Chiral BrOnsted acid-catalyzed Friedel-Crafts-type reactions of indole and its derivatives with various carbon-centered electrophiles e.g. electron deficient olefins, carbonyls, imines and some substituted methanamines and carbinols have been employed to prepare optically active indole derivatives. These reactions, their stereochemical outcome and probable modes of activation of the substrates by suitably substituted axially dissymmetric BINOL-derived chiral BrOnsted acid catalysts are discussed in this review.

Influenza can affect the health of human being and it is considered as the most serious respiratory disease. (–)-Oseltamivir phosphate, also popularly known as Tamiflu, has been reported to be one of the most potent chemotherapeutic agents with oral activity. It can inhibit the viral neuraminidase enzyme to catalyze the cleavage of the sialic acid residue from glycoproteins, thus preventing the infected cells to liberate the proliferated viruses. The industrial production method for oseltamivir phosphate uses (–)-shikimic acid as the starting material, which is a natural product isolated from a plant of Chinese star anise (belonging to the Illicium family). However, because the (–)-shikimic acid is unavailable in consistent purity and sufficient quantity, many chemists have dedicated some new synthetic routes to prepare this drug for the treatment of influenza disease. In this article, the reported synthetic approaches for (–)-oseltamivir phosphate since 2011 are reviewed, and the representative results are described in chronological order.

Recent developments in the microwave-assisted synthesis of carbo- and heterocyclicsystems are reviewed with the focus on diversity-oriented cycloaddition reactions. Ineed, these reactions represent one of the most important endeavors in chemistry and are of considerable interest in the synthesis of carbo-and heterocyclic compounds from simple unsaturated systems, and allow the creation of more than two bonds in one step. This review summarizes recent literature (2006-2013) on advances regarding [3+2], [4+2] and [2+2] cycloadditions including their miscellaneous version. Advantages of microwave dielectric heating are highlighted by comparison with conventional thermal conditions. In particular, we describe here the microwave effect, reaction media including solvent-free transformations and more ecological processes in the context of green and environmentally benign chemistry.