Ignacio Delso

■ Recent Advances on the Synthesis of Piperidines through Ruthenium-Catalyzed Ring-Closing Metathesis (RCM) Reactions

Ring-closing metathesis reactions of dialkenyl amines, amides and carbamates catalyzed by Ru-catalysts provide efficient approaches to six-membered nitrogen heterocyclic compounds, which are precursors of a variety of natural products and related compounds. Abstract Monoterpene indole alkaloids comprise a group of naturally occurring compounds, exhibiting a range of biological activities. These compounds have attracted great attention because of their interesting biosynthetic route and also as a challenging target for total synthesis. For such synthetic approach and structure - activity relationship studies, the knowledge about their absolute stereostructures is essential. This review summarizes the presently available results of studies on the determination of the absolute configuration of indole alkaloids by the use of circular dichroism (CD).

Current Developments in the Synthesis and Biological Activity of Aza-C-Nucleosides:Immucillins and Related Compounds

This review will describe the recent advances in the field of aza-C-nucleosides with a particular emphasis on immucillins and related compounds. The review will cover both chemical and biological aspects concerning their preparation and/or occurrence in Nature as well as their biological properties which include glycosidase, glycosyl transferase, and nucleoside hydrolase and phosphorylase inhibition, among others. These enzymatic inhibitory properties are the basis for the potential use of the title compounds in viral and parasitic infections, cancer and genetic disorders.

Chemistry and Biology of Iminosugar Di- and Oligosaccharides

This review will describe the recent advances in the field of oligosaccharides containing at least one unit of a polyhydroxylated piperidine or pyrrolidine. The review will cover both chemical and biological aspects concerning their preparation and/or occurrence in Nature as well as their biological properties which include glycosylase, and glycosyl transferase inhibition, among others. These enzymatic inhibitory properties are the basis for the potential use of the title compounds in viral infections, cancer and genetic disorders.

Recent progress on fucosyltransferase inhibitors.

Fucosyltransferases (FucTs) are enzymes that transfer L-fucose from GDP-fucose to a glycoside or a peptide. They have important roles in a variety of diseases including cancer and autoimmune disorders, viral and bacterial infections and inflammatory processes, and thus they represent important drug targets for the development of agents for the treatment of such disorders. This review highlights recent developments regarding carbohydrate mimics as inhibitors of FucTs. The most recent and relevant synthetic strategies are described.

Regioselectivity change in the organocatalytic enantioselective (3+2) cycloaddition with nitrones through cooperative hydrogen-bonding catalysis/iminium activation

The reaction of nitrones with enals through iminium activation can be modulated by using cooperative hydrogen-bonding catalysis to induce the participation of a nitrone ylide (C-N-C) instead of the classical C-N-O dipole. As a consequence, N-hydroxypyrrolidines are obtained, rather than the expected isoxazolidines. The reaction proceeds smoothly and high enantioselectivities are observed in all cases. By using the appropriate substrate, polysubstituted pyrrolidines incorporating quaternary stereocenters can be efficiently prepared.

Introducing topology to assess the synchronicity of organic reactions. Dual reactivity of oximes with alkenes as a case study

The synchronicity of organic reactions not always can be determined by only the analysis of transition structures. We present a case study that illustrates that topological analyses provide information regarding synchronicity that, often, is not reflected in the geometry of transition structures. We have chosen the competitive reactions of oximes with alkenes, (3 + 2) dipolar cycloaddition and ene-like reaction, which have been computationally studied to determine the parameters favoring each process. The competition between the two reactions is particularly evidenced in alkenyl oximes leading to intramolecular processes. Up to 26 examples of intramolecular reactions have been calculated and the results predicted the favored process.

Chemical approaches to inhibitors of isoprenoid biosynthesis: targeting farnesyl and geranylgeranyl pyrophosphate synthases

Post-translational lipid modifications farnesylation and geranylgeranylation of proteins (protein prenylation) have been identified to mediate critical events in cancer, cardiovascular disorders, malaria and bone disorders like osteoporosis. To date eight compounds are commercialized for the treatment of bone disorders, and there are considerable efforts to develop selective small molecules that inhibit protein prenylation. This review summarizes the approaches currently employed to synthesize new inhibitors of isoprenoid biosynthesis. Bisphosphonates are mainly prepared through reaction of carboxylic acids with phosphorus reagents, Michael addition to tetraethylvinylidenebisphosphonate and alkylation of tetralkylmethyl bisphosphonate. Approaches to non-bisphosphonate derivatives include a variety of methodologies depending on the structure of the target compound.

UDP‐GlcNAc Analogues as Inhibitors of O‐GlcNAc Transferase (OGT): Spectroscopic, Computational, and Biological Studies

A series of glycomimetics of UDP-GlcNAc, in which the β-phosphate has been replaced by either an alkyl chain or a triazolyl ring and the sugar moiety has been replaced by a pyrrolidine ring, has been synthesized by the application of different click-chemistry procedures. Their affinities for human O-GlcNAc transferase (hOGT) have been evaluated and studied both spectroscopically and computationally. The binding epitopes of the best ligands have been determined in solution by means of saturation transfer difference (STD) NMR spectroscopy. Experimental, spectroscopic, and computational results are in agreement, pointing out the essential role of the binding of β-phosphate. We have found that the loss of interactions from the β-phosphate can be counterbalanced by the presence of hydrophobic groups at a pyrroline ring acting as a surrogate of the carbohydrate unit. Two of the prepared glycomimetics show inhibition at a micromolar level.