Alessandro Dondoni

Asymmetric Organocatalysis : From Infancy to Adolescence

After an initial period of validating asymmetric organocatalysis by using a wide range of important model reactions that constitute the essential tools of organic synthesis, the time has now been reached when organocatalysis can be used to address specific issues and solve pending problems of stereochemical relevance. This Review deals with selected studies reported in 2006 and the first half of 2007, and is intended to highlight four main aspects that may be taken as testimony of the present status and prospective of organocatalysis: a) chemical efficiency; b) discovery of new substrate combinations to give new asymmetric syntheses; c) development of new catalysts for specific purposes by using mechanistic findings; and d) applications of organocatalytic reactions in the asymmetric total synthesis of target natural products and known compounds of biological and pharmaceutical relevance.

Calixarene and Calixresorcarene Glycosides: Their Synthesis and Biological Applications

It is firmly established that cell surface carbohydrate-protein interactions are at the forefront of a myriad of vital cellular events.1 Such interactions, however, are usually weak, with KD values of the order of mM for monosaccharides. However, when a set of multivalent saccharides is clustered together with the right structure and spatial disposition, the interaction becomes strong and specific. This augmented association is more than what would be expected on the basis of the increased carbohydrate local concentration, and it has been termed glycoside cluster effect.2 It is quite obvious that in order to intervene efficiently on these interactions, multivalent external agents have to be employed. In this context, one can envisage the use of glycoclusters firmly anchored to a conformationally rigidified calixarene or calixresorcarene scaffold as suitable systems for protein recognition and consequently protein activity inhibition. This is especially important in those cases in which carbohydrateprotein interactions are detrimental such as viral and bacterial infections, inflammations, and cancer metastasis. The aim of this review is to present the various approaches that have been carried out for the synthesis of multivalent calixarene and calixresorcarene glycosides (calixsugars) displaying different anomeric linkages and carbohydrate-macrocycle tethers. The validation of the biological activity of suitably designed calixsugars as well as of complex molecular systems in which they were introduced will be also reported. The synthesis and biological applications of calixarene glycoconjugates represented a new way of considering * To whom correspondence should be addressed. E-mail: adn@unife.it (A.D.); mra@unife.it (A.M.). Alessandro Dondoni has been Professor of Organic Chemistry at the University of Ferrara from 1975 to 2008. At present he is Senior Scientist at the same University. He has been the recipient of several awards, including A. Mangini Gold Medal from the Italian Chemical Society (1996), Avogadro-Minakata Lectureship Award of the Chemical Society of Japan (1999), Ziegler-Natta Lectureship Award of the German Chemical Society (1999), Lincei National Academy Prize in Chemistry (1999), and G. Berti Gold Medal from the Italian Chemical Society (2010). His present research interests are in new synthetic methods, organocatalysis, and carbohydrate chemistry. He recently started a new program dealing with the use of free-radical thiol-ene coupling as a click ligation tool for peptide and protein modification. A large part, if not all, of his chemistry is being developed with the aim of providing new products for biochemical studies and pharmaceutical and biomedical applications. Chem. Rev. 2010, 110, 4949–4977 4949

Parallel synthesis of dihydropyrimidinones using Yb(III)-resin and polymer-supported scavengers under solvent-free conditions. A green chemistry approach to the Biginelli reaction

An efficient synthesis of an array of 3,4-dihydropyrimidin-2-(1H)-ones using solid-supported ytterbium(III) reagent from aldehydes, 1,3-dicarbonyl compounds and urea (Biginelli reaction) under solvent-free conditions is described. Purification of each member of the library was carried out using a cocktail of acid and basic polymer-supported scavengers

Synthesis of N-Benzyl Nitrones

Abstract A general procedure for the synthesis of twenty-seven chiral and achiral N-benzyl nitrones 1 is described.

Validation of the copper(i)-catalyzed azide-alkyne coupling in ionic liquids. Synthesis of a triazole-linked C-disaccharide as a case study.

The first study of a copper(I)-catalyzed azide-alkyne click reaction in ionic liquids (ILs) is reported. The cycloaddition of a sugar azide with a sugar acetylene (CuI, i-Pr2EtN, 80 degrees C) was carried out in 10 ILs as well as in standard molecular solvents (toluene and DMF) to give the 1,4-disubstituted triazole-linked C-disaccharide. The highest yields (84 and 95%) were registered in Ammoeng 110 and [C(8)dabco][N(CN)(2)]. The latter solvent was recycled in four subsequent reactions without loss of the reaction efficiency. Reactions carried out in the absence of the Hünigs base afforded mixtures of 1,4- and 1,5-disubstituted triazole regioisomers.

A New Ligation Strategy for Peptide and Protein Glycosylation: Photoinduced Thiol–Ene Coupling

or benefi-cial (immune response, fertilization). The isolation of glyco-peptides and glycoproteins with a well-defined carbohydratestructure from natural sources is difficult and even with cur-rent techniques virtually impossible. This is due to two mainfactors, that is, the oligosaccharide microheterogeneity pro-duced by the presence of various glycoforms and the verylabile N- and O-acetal bonds which are the most diffuseconnections between the terminal carbohydrate of the oligo-saccharide fragment and asparagine or serine/threonine resi-due, respectively. Therefore it is difficult to identify the spe-cific oligosaccharide structures that are responsible of an in-dividual biological process or protein function. Hence thereis an urgent need for the preparation of non-natural glyco-peptides and glycoproteins exhibiting robust anomeric link-ages and a well defined structure and composition. Thesehomogeneous materials are likely to improve our under-standing of the role of the natural counterparts in biologicalevents and can be interesting drug candidates in differentareas of medicine. Methods for the synthesis of glycopepti-des exploiting various peptide-ligation protocols based onchemoselective reactions have been chronicled in recentyears.

Photoinduced Thiol-Ene Coupling as a Click Ligation Tool for Thiodisaccharide Synthesis

The high efficiency and selectivity of the thiol-ene radical reaction has been validated by the photoinduced coupling of anomeric sugar thiols with sugar alkenes to give 1,6-linked S-disaccharides in good to excellent yields (76-92%) and high diastereoselectivities (up to 99%). The reaction appears to be well-qualified as an exemplar click process.

Photoinduced Addition of Glycosyl Thiols to Alkynyl Peptides: Use of Free-Radical Thiol−Yne Coupling for Post-Translational Double-Glycosylation of Peptides

Double glycosylation of cysteine-containing peptides has been carried out by a one-pot two-step sequence comprising selective S-propargylation followed by photoinduced (lambda (max) 365 nm) free-radical hydrothiolation with glycosyl thiols. Conditions were established for the sequential introduction of two different thiol residues such as a glycosyl and a biotinyl derivative.

Porphyrins in 1,3-dipolar cycloaddition reactions with sugar nitrones. Synthesis of glycoconjugated isoxazolidine-fused chlorins and bacteriochlorins

Glycoconjugated isoxazolidine-fused chlorins and bacteriochlorins were prepared in moderate to good yields by 1,3-dipolar cycloaddition reactions of meso-tetrakis(pentafluorophenyl)porphyrin with glycosyl nitrones.

Design of Triazole‐Tethered Glycoclusters Exhibiting Three Different Spatial Arrangements and Comparative Study of their Affinities towards PA‐IL and RCA 120 by Using a DNA‐Based Glycoarray

Sugar‐coated chips: Glycoside clusters are valuable tools for carbohydrate–lectin recognition studies. However, the spatial arrangement of the sugar residues is a key issue in the design of high‐affinity glycoclusters. Here the affinities of linear and antenna‐ and calixarene‐based galactoside clusters towards two lectins derived from Pseudomonas aeruginosa and Ricinus communis were compared by means of glycoarrays.