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Direct hydroxymethylation of C=N double bonds including imines, nitrones, oximes, hydrazones and iminium salts is a less explored synthetic approach to 1,2-amino alcohols that provides good alternatives to the classical methods. The review deals with nucleophilic additions of organometallic hydroxymethyl reagents and lithiated alkoxyallenes to C=N double bonds. Reductive cross couplings between C=N double bonds and aldehydes or ketones are also discussed.

The reactivity of nitrones in cycloadditions and related reactions is revisited by introducing a topological perspective. In particular, the study of electron localization function (ELF) along a reaction pathway allows evaluating bond reorganization showing that in several cases the bonds are formed in a sequential way, the second one being formed once the first one is already formed. Both classical 1,3-dipolar cycloadditions and Mannich-type reactions revealed unexpected features often underestimated in classical mechanistic studies., This work was supported by the MINECO and FEDER Program (Madrid, Spain, project CTQ2016-76155-R) and the Gobierno de Aragon (Zaragoza, Spain. Bioorganic Chemistry Group. E-10).

The reaction of aromatic nitroso derivatives with enolizable carbonyl compounds (nitroso aldol reaction) to give either α-hydroxyamino or α-aminoxy carbonyl compounds is an important synthetic method. This review illustrates the recent advances in rendering the process regio- and enantioselective as well as catalytic. By employing metal and organic catalysts a range of α-amino (α-oxyamination) and α-hydroxy (α-aminoxylation) carbonyl derivatives can be generated with total regioselectivity and high levels of enantiomeric excess. 1 Introduction 2 Metal-Catalyzed Reactions 3 Organocatalyzed Reactions 4 Enamine Metal-Free Reactions 5 Concluding Remarks

The reaction of aromatic nitroso derivatives with enolizable carbonyl compounds (nitroso aldol reaction) to give either α-hydroxyamino or α-aminoxy carbonyl compounds is an important synthetic method. This review illustrates the recent advances in rendering the process regio- and enantioselective as well as catalytic. By employing metal and organic catalysts a range of α-amino (α-oxyamination) and α-hydroxy (α-aminoxylation) carbonyl derivatives can be generated with total regioselectivity and high levels of enantiomeric excess., We thank for their support of our programs: MINECO (Madrid, Spain) and FEDER Program (Project CTQ2013-44367-C2-1-P) and the Government of Aragon, Spain (Bioorganic Chemistry Group E-10).

This review covers the recent advances in the synthesis of enantiomerically pure hydroxylamine’s employing nitrones as starting materials. Nucleophilic additions of organometallic reagents to nitrones are the most common way for introducing a hydroxyamino group into carbon skeletons with the concomitant formation of a new carbon-carbon bond. Addition of nucleophiles derived from enolates, cyanide or fluorinated derivatives allows the preparation of complex structures. Radical additions and, in particular samarium diiodidemediated reductive coupling of nitrones with carbonyl compounds and α,β-unsaturated esters have also been considered. All these approaches provide efficient methods of preparation of enantiomerically pure hydroxylamine’s that are valuable synthetic intermediates., We thank for their support of our programs: MINECO (Madrid, Spain) and FEDER Program (Project CTQ2013-44367-C2-1-P) and the Government of Aragon (Group E-10). H.H. thanks UE (Erasmus program) for a mobility grant. M.G. thanks MECD for a FPU pre-doctoral grant.

The use of dopaminergic agonists is key in the treatment of Parkinson's disease and related central nervous system (CNS) neurodegenerative disorders. Despite there are a number of commercialized dopaminergic agonists that are currently being used successfully in the first stages of the disease, they often fail to provide sustained clinical benefit for a long period due to the appearance of side-effects such as augmentation, sleepiness, nausea, hypothension, and compulsive behaviors among others. New dopaminergic agonists with less side effects are being developed. These novel compounds offer an alternative when the disease progresses and patients fail to respond to standard dopaminergic treatments or side-effects increased. Chemistry, and in particular chemical synthesis, has played a major role in bringing synthetic dopaminergic agonists to the clinic and continues to be crucial for the development of new and necessary drugs for long-term treatments with less undesired side effects. A number of structural modifications of parent compounds have led to enhanced agonism but also partial agonism or even antagonism of one or more dopamine receptors. In some cases, these activities are accompanied by agonist effect at serotonin receptors which suggests a potential clinical application in the treatment of schizophrenia In this review, chemical synthesis of dopaminergic agents, their affinity, and the corresponding agonist/antagonist effects will be highlighted.

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.

This review will describe the recent advances in the synthesis of C-nucleosides with inhibitory activity of inosine monophosphate dehydrogenase (IMPDH), a key enzyme in the biosynthesis of guanine nucleotides. The review will cover synthetic approaches of structural analogues showing modifications in the furanose ring as well as in the heterocyclic base. Heterocyclic sugar nucleoside analogues in which the furanose ring has been replaced by a different heterocyclic ring including aza analogues, thioanalogues as well as dioxolanyl and isoxazolidinyl analogues are also considered.

The diastereoselective 1,3-dipolar cycloadditions of achiral nitrones (I) with chiral acrylamide (II) is compared with the corresponding cycloadditions of chiral nitrones (V) with methyl acrylate.

This review will describe the recent advances in the synthesis of C-nucleosides with inhibitory activity of inosine monophosphate dehydrogenase (IMPDH), a key enzyme in the biosynthesis of guanine nucleotides. The review will cover synthetic approaches of structural analogues showing modifications in the furanose ring as well as in the heterocyclic base. Heterocyclic sugar nucleoside analogues in which the furanose ring has been replaced by a different heterocyclic ring including aza analogues, thioanalogues as well as dioxolanyl and isoxazolidinyl analogues are also considered. © 2014 Bentham Science Publishers., This study was supported by the Ministerio de Ciencia e lnnovacion (MICINN) and FEDER Program (Madrid, Spain, project CTQ2010-19606) and the Gobierno de Aragon (Zaragoza, Spain, Bioorganic Chemistry Group. E-10). M.G. thanks MEC for a FPU predoctoral grant.

Peptide nucleic acid (PNA) 1 (Figure 1) is an oligopeptide with nucleobases linked together by an achiral, uncharged aminoethylglycine backbone (aeg-PNA), that binds strongly and in a sequence-specific manner to complementary DNA and RNA oligonucleotides.1 PNA is formed by repetition of a tri-branched unit recalling the sicilian Trinacria.2 Since its discovery in 1991 by Nielsen and co-workers,3 PNAs have became important mimics of natural nucleic acids with application as antisense and antigen agents4 and as biomedical diagnostic tools.5,6 Although PNAs were designed initially to recognize dsDNA via triplex formation in the major groove by Hoogsteen pairing,3 very efficient mimics resulted that bind their sequence-complementary targets in both parallel and antiparallel orientation by Watson–Crick pairing.7 Moreover, PNAs bind in invasive modes to give PNA/DNA duplexes and PNA2–DNA or high-order complexes.8 PNAs bind to DNA and RNA with markedly higher thermal stability relative to any other modified oligonucleotide from synthetic or natural sources.9,10 Despite these promising features and successful experiments demonstrating that PNAs are capable of inducing transcription and translation inhibition,11 the therapeutic development of PNAs into drugs is seriously compromised by their limited solubility in physiological media.12 In pursuit of improved binding affinity of PNAs and to increase their water solubility, different classes of conformationally constrained analogues have been designed.13 Among these families of

Diastereoselective asymmetric 1,3-dipolar cycloadditions of N-(alkoxycarbonylmethyl) nitrones derived from glycine, alanine and phenylalanine have been studied both experimentally and theoretically. Asymmetric induction is evaluated by either introducing a chiral group at the nitrone nitrogen atom or by using Oppolzer's sultam acrylamide. In both cases the sense of the asymmetric induction is the same, the (3R,5R)-isomer being preferentially obtained. The best results were observed with the chiral dipolarophile, which afforded an only isomer in all cases. The obtained isoxazolidines are easily transformed into the corresponding 5-substituted-3-hydroxypyrrolidin-2-ones. DFT studies are in a qualitative agreement with the observed experimental results. © 2013 Elsevier Ltd. All rights reserved., This study was supported by the Ministerio de Ciencia e Innovación (MICINN) and FEDER Program (Madrid, Spain, projects CTQ2010-19606 and BFU2010-19504) and the Gobierno de Aragón (Zaragoza, Spain. Bioorganic Chemistry Group. E-10). We thank MIUR (Italy) and CNMPS (Italy) for their financial support. G.C. thanks MICINN for a contract and University of Palermo for a pre-doctoral grant.

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).

Activation of imines by hydrogen bonding is a very powerful way of promoting the synthesis of a variety of nitrogencontaining compounds of interest. Such a useful approach typically involves mild reaction conditions, simple experimental operations and metal-free reagents. The present review focuses on the recent development of new organocatalytic methods involving imines and related compounds as substrates in which activation through hydrogen bonding is performed. The different modes of activation are thoroughly illustrated with special emphasis on mechanistic aspects of the reactions and how activation is actually produced. © 2011 Bentham Science Publishers Ltd.

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.

Oxidation reactions of several furan derivatives as effective methods for the preparation of key synthetic inter- mediates are reviewed. Depending on the oxidizing reagent the furan ring can be considered as a C-1 or C-4 synthon, which upon different conditions leads to 1,4-dicarbonyl compounds, carboxylic acids, pyranones or butenolides.

Oxidation reactions of several furan derivatives as effective methods for the preparation of key synthetic intermediates are reviewed. Depending on the oxidizing reagent the furan ring can be considered as a C-1 or C-4 synthon, which upon different conditions leads to 1,4-dicarbonyl compounds, carboxylic acids, pyranones or butenolides.

Se han analizado las inmisiones de ozono de la ciudad deZaragoza entre 2002-2008 a partir de los promedios diarios registradosen tres estaciones de seguimiento. La evolución interanual muestra elpatrón de máximo de verano y mínimo de invierno, y en el periodo analizadomuestra un aumento de las inmisiones. El calendario diario promediopermite observar las Diferencias entre el día y noche, que seacentúan en el verano. El estudio de los valores promedio diarios semanalesrefleja con claridad un aumento durante el fin de semana. En ningúnmomento los valores de inmisión han superado los umbrales legalesestablecidos, por lo que se puede afirmar que la ciudad no sufreproblemas por este contaminante.

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.

The reaction of N-benzyl-C-(alkoxymethyl) nitrones with lithium and sodium enolates derived from menthyl and bornyl acetates affords mixtures of hydroxylamines and isoxazolidin-5-ones. On the other hand, the reaction with the silyl ketene acetals prepared from the above-mentioned acetates mainly affords the silylated hydroxylamines. In both cases the crude reaction mixtures can be smoothly transformed into enantioenriched mixtures of 3-(alkoxymethyl) isoxazolidin-5- ones which are key intermediates in the synthesis of isoxazolidinyl nucleosides.