Current Organic Chemistry - Volume 18, Issue 12, 2014

Owing to the interest that γ-lactams (pyrrolidin-2-ones) deserve for medicinal and natural products chemistry, the development of novel methodologies for synthesis and decoration of the heterocyclic core has become the objective of many synthetic chemists. This review is presented in two parts: whereas Part I highlighted efficient synthetic strategies directed towards lactam ring formation, Part II deals with transformations of γ-lactams (issued between 2001 and 2013) involving introduction of new chains or functional groups or modification of the preexisting ones. Enantioselective synthesis is particularly emphasized, since polysubstituted enantiomerically pure γ- lactams are important for biological testing or can be key intermediates for preparation of bioactive natural products.

Aza heterocycles comprise some rousing structures in biological systems. The aza-Diels-Alder reaction is a [4Π +2Π] cycloaddition, involving a nitrogen atom in either diene or dienophile or both for the generation of unsaturated N-hexacycles. Although aza- Diels-Alder reaction has made a wonderful journey through different stages of development it is still considered as one of the hot topics of research because of procedural simplicity, high atom economy, regio- and stereoselectivity. Building blocks of many pharmaceutically as well as pharmacologically vital heterocycles have come out as a result of application of aza-Diels-Alder protocol in numerous chemical reactions. This review article describes the state of the art of the aza-Diels-Alder reactions highlighting some of the very first discovery of this pericyclic reaction to most important modern developments. Our discussion is highly focused on awesome versions of aza- Diels-Alder reaction under selected and magnificent catalytic systems and, will provide readers an overview on versatility of this special branch of Diels-Alder reaction towards the creation of a flood of N-containing molecules.

Nucleoside tetraphosphates perform numerous functions in a wide variety of living species from bacteria to complex eukaryotes. In human beings, various nucleoside tetraphosphates have been shown to serve as agonists for a variety of purogenic receptors and kinases, influencing intraocular pressure, platelet activation, vasoconstriction, and extracellular signaling. Also, they are involved in cell division, and bacteria growth and development. Synthetic derivatives can be used in discovery to explore their in vivo function, or in the development of more powerful receptor agonists and kinase inhibitors. They also show promise in such fields as drug delivery and nucleic acid assays. Although nucleoside polyphosphates can refer to phosphates attached at multiple hydroxyl positions on the same ribose moiety of deoxyribo- or ribonucleosides, here we concentrate on the syntheses of nucleosides attached to a tetraphosphate moiety, where the tetraphosphate chain can serve as a single adduct or as a linker between two nucleosides or a nucleoside and another moiety. Syntheses to create these important molecules and their derivatives have included both chemical and enzymatic approaches. Each approach has its own pros and cons. Chemical synthesis allows the creation of products with highly diverse structures enabling structure-activity relationship (SAR) studies. However, these often require multiple protection-deprotection steps, which can be synthetically challenging. Enzymatic synthesis, on the other hand, allows a targeted reaction with no protecting group chemistry involved, but it is limited in its substrate specificity and in its chemo- and regioselective products and can be prohibitively expensive for large- scale production. This comprehensive review covers the evolutionary progress in synthesizing various nucleoside tetraphosphates since the discovery of the first example, adenosine 5'-tetraphosphate, in 1953. It compares the advantages and limitations among the different approaches. The intent of this review is to provide researchers both a primer and a reference for the best method for their own syntheses. We hope it will encourage more in-depth biological studies and broaden the biological applications of these molecules.

Deoxyribonucleic acid (DNA), an intrinsic intumescent flame retardant system, able to behave as a char-former, has been melt-blended with an ethylene vinyl acetate copolymer (EVA) at different concentrations (namely, 10, 15 and 20wt.-%). The thermal and fire stability of the obtained compounds has been thoroughly investigated through thermogravimetric analyses (in nitrogen and air), limiting oxygen index and cone calorimetry tests. Furthermore, in order to provide an additional carbon source and thus to reduce the DNA content, α-cellulose or β-cyclodextrins have been used. DNA has promoted a significant reduction of the Heat Release Rate peak (-40%) as well as of CO and CO2 yields (approximately -50 and -40%, respectively), slightly increasing, at the same time, the residue after the cone calorimetry tests. The addition of α-cellulose to DNA/EVA compounds has clearly proved that this carbon source can significantly reduce the DNA content required for conferring flame retardant features to the copolymer, thus demonstrating a cumulative (not synergistic) effect exerted by the presence of the two additives, as also revealed by the estimation of the synergistic effectiveness parameter.

The reactions of 2-iodo-α-methyl styrene (S1) with diphenyl acetylene (S2) (equation 1) and iodo-benzene (S3) with diphenyl acetylene (S2) (equation 2) have been theoretically studied with the aid of density functional theory calculations. Equation 1 reaction involves four major steps, aryl-I oxidative addition, alkyne insertion, C=C bond insertion, and (sp3)C-I reductive elimination. Equation 2 reaction involves aryl-I oxidative addition, alkyne insertion, and further alkyne insertion. Based on the mechanistic study, we revealed why the indene product P could be obtained in equation 1 while the proposed product P2 could not be obtained in equation 2. In addition, the bulkiness of the ligand PtBu3 plays an important role for the steps involved undergoing mono-L or non-L paths.