Aida Flores

Update 1 of: α,β-Diamino Acids: Biological Significance and Synthetic Approaches

The discovery of nonproteinogenic amino acids among natural products, either in native state or as fragments of complex molecules, has increased the level of interest in this family of molecules from different scientific standpoints. Compounds with valuable biological properties can be found among these atypical amino acids. In addition, they have served as building blocks for the synthesis of new molecules or as surrogates of native amino acids in known peptidic entities to modulate their biological behavior. In this context, R, -diamino acids and their derivatives esters and amides, have attracted a great deal of attention among organic chemists and biochemists through the years. This interest has been due to the ubiquitous nature of R, -diamino acids as key structural fragments of biologically active compounds. Beyond this focus, the simplest compound, 2,3-diaminopropionic acid, has recently found application in the environmentally safe production of hydrogen for fuel cells, as a selective carrier of CO2 through gel membranes.1a Also, it has served to assemble a molecular device that produces propelling motion upon IR irradiation1b and, lately, in the context of food chemistry, 2,3-diaminopropionic acid has been identified as an inhibitor of polyphenol oxidase, the enzyme responsible for the browning of fruits and vegetables1c and as an enhancer of Maillard browning.1d In spite of the incidence of these molecules in an increasing number of areas, this review will deal with the biological significance, the therapeutic uses, and other interesting applications of R, -diamino acids and their derivatives found in the existing literature. Additionally, aside from the above considerations, the structural complexity of these molecules, having two vicinal chiral centers has also represented a challenge for synthetic organic chemists, especially the synthesis of enantiopure materials. Therefore, the aim of this article will also be to provide a deep and general view of the existing methodology for the synthesis of aliphatic R, or 2,3-diamino acids and their simple derivatives, esters, * To whom correspondence should be addressed. E-mail: iqov379@ iqog.csic.es. Alma Viso was born in Madrid (Spain) in 1964. She obtained a B.S. degree in Chemistry in 1987 and a Ph.D. in 1992 from Universidad Complutense de Madrid (UCM). In 1992, she moved to Massachusetts Institute of Technology (MIT) as a Fulbright fellow to work with Stephen L. Buchwald for 18 months. She joined the faculty at UCM (Madrid) in 1993 as an Assistant Professor and was promoted to Associate Professor in May 2002. In December 2002, she joined Instituto de Quı́mica Orgánica General, CSIC, as a Staff Researcher (Cientı́fico Titular) and was promoted to Senior Staff Researcher (Investigador Cientı́fico) in 2007. Her current research interests are focused in two main areas, the development of new methodologies in asymmetric synthesis using sulfoxides and sulfinamides and the application of these novel methods to efficient syntheses of therapeutically valuable products. Chem. Rev. PR1

Entry Inhibitors Directed Towards Glycoprotein gp120: An Overview on a Promising Target for HIV-1 Therapy

In spite of the unquestionable positive impact of HAART in the treatment of HIV infection, the discovery and development of novel agents directed towards other targets of the replicative cycle of the virus that differ from those targeted by the clinically approved drugs, emerges nowadays as an imperative need. The blockade of HIV entry is a highly promising strategy against the pathogen and glycoprotein gp120 is a central actor in this process. This review discusses the current status in the research of anti-HIV agents targeting specifically the envelope protein gp120. The diverse approaches devoted to the achievement of therapeutic agents against gp120 currently under study are organized and analyzed critically according to their specific mechanism of inhibition and structural features.

The overlooked role of reduced graphene oxide in the reinforcement of hydrophilic polymers

The covalent incorporation of reduced graphene oxide into a hydrophilic polymer demonstrates that, contrary to current opinion, reinforcement can be attributed to a change in water affinity. Advanced nanoindentation techniques show that the deterioration of the mechanical properties of poly(vinyl alcohol) under high relative humidity can be avoided by incorporating a small quantity of reduced graphene oxide at molecularly controlled locations.

Structure-activity relationship studies on a Trp dendrimer with dual activities against HIV and enterovirus A71. Modifications on the amino acid

&NA; We have recently described a new class of dendrimers with tryptophan (Trp) on the surface that show dual antiviral activities against HIV and EV71 enterovirus. The prototype compound of this family is a pentaerythritol derivative with 12 Trps on the periphery. Here we complete the structure‐activity relationship studies of this family to identify key features that might be significant for the antiviral activity. With this aim, novel dendrimers containing different amino acids (aromatic and non‐aromatic), tryptamine (a “decarboxylated” analogue of Trp) and N‐methyl Trp on the periphery have been prepared. Dendrimer with N‐Methyl Trp was the most active against HIV‐1 and HIV‐2 while dendrimer with tyrosine was endowed with the most potent antiviral activity against EV71. This tyrosine dendrimer proved to inhibit a large panel of EV71 clinical isolates (belonging to different clusters) in the low nanomolar/high picomolar range. In addition, a new synthetic procedure (convergent approach) has been developed for the synthesis of the prototype and some other dendrimers. This convergent approach proved more efficient (higher yields, easier purification) than the divergent approach previously reported. Graphical abstract Figure. No caption available. HighlightsNovel dendrimers containing different amino acids on the periphery have been synthesized.These compounds have dual action against HIV and EV71.Tyrosine dendrimer is the most potent against EV71 while dendrimer with N‐methyl Trp is the most potent against HIV‐1.Dendrimer with tyrosine is an extremely highly potent inhibitor of clinical EV71 isolates (nanoMolar‐picoMolar potency).Presence of hydrophilic groups (NH, OH) on the aromatic ring of the amino acid is beneficial for anti‐EV71 activity.

Highly Diastereoselective [3+2] Cycloadditions Between Non-Racemic p-Tolylsulfinimines and Iminoesters: An Efficient Entry to Enantiopure Imidazolidines and Vicinal Diaminoalcohols

Abstract Readily available p-tolylsulfinimines undergo highly stereoselective [3 + 2] cycloadditions with azomethine ylides generated from α -iminoesters and LDA to produce N-sulfinylimidazolidines. In the presence of Lewis acids, p-tolylsulfinimines react with glycine iminoester enolates to produce N-sulfinylimidazolidines, after cyclization of open chain intermediates. These mechanistically diverse processes take place with excellent regio-, stereo-, and facial selectivities, and the latter is opposite to most known reactions involving sulfinimines. Some of the resulting imidazolidines have been transformed into examples of a novel class of nonsymmetrical vicinal diamines using reductive and/or hydrolytic protocols.