Andrea Basso

Solid-phase dendrimer synthesis

Dendrimers are highly ordered, hyperbranched polymers with potential for a whole range of chemical applications. Solution‐phase synthesis of dendrimers is often challenging, requiring long reaction times and nontrivial purification; solid‐phase methodology, on the other hand, enables reactions to be driven to completion by using a large excess of reagents with trivial purification. In this paper we show that polyamidoamine dendrimers may be synthesized conveniently and efficiently on a solid support, and that these molecules are of good homogeneity as characterized by 1H‐ and 13C‐nmr and electrospray mass spectrometry. These solid‐phase dendrimers were used as a bead loading amplification tool in the synthesis of a hexapeptide library (Xaa–Gly–Gly–Phe–Leu–Lys) to allow single bead analysis as well as allowing the efficient synthesis of two dendrimer conjugates (Leu–enkephalin–Lys and Chlorambucil). This demonstrated that peptides and small drug molecules can be grown directly onto the dendrimer or onto a linker attached to the dendrimer periphery, enhancing general dendrimer utility.

Solid-phase Friedel–Crafts acylation on polystyrene resins-synthesis of antiepiletic 1-aryl-3,5-dihydro-4H-2,3-benzodiazepin-4-ones

Abstract Friedel–Crafts acylation with various acyl chlorides of resin-bound 3,4-dimethoxyphenylacetate afforded resin bound ketones which, following treatment with hydrazine, were converted into the corresponding 2,3-benzodiazepines in good yields and purities.

Solid-phase synthesis of aryl ethers on high loading dendrimer resin

Resin-bound dendrimers have the potential to increase bead loading by at least one order of magnitude. In this letter we report the solid-phase synthesis of a library of aryl ethers using high-loading dendrimer beads, and compare the synthetic efficiency with that of TentaGel (Polystyrene-PEG) resin.

New Approach to β-Lactam-Fused Enediynes (“Lactenediynes”) by Stereoselective Pinacol Coupling

A short synthesis of unfunctionalized lactenediyne 3 by closure of the ten-membered ring at the double bond site is reported. After failure of the known methodologies, this closure was eventually successfully achieved thanks to a highly stereoselective, vanadium(II)-mediated pinacol coupling of bis(alk-2-ynal) 7.

Solid-phase synthesis of amidine-based GP IIb-IIIa antagonists on dendrimer resin beads

Many amidine-based molecules are known to be antagonists of the fibrinogen-GP IIb-IIIa interaction, therefore useful in the treatment of thrombotic deseases. Here we report the solid-phase synthesis of a small library of amidines, starting from high-loading dendrimerised TentaGel beads, using resin-bound 4-amidinobenzoic acid as a template. These compounds mimic the structure of known active compounds like Lamifiban (Ro44-9883) and TAK-029; the first solid-phase synthesis of which is also reported in this paper.

Solid phase synthesis of aryl-ether dendrimers

Solid phase chemistry can be used to prepare, in excellent nyield and purity, a range of Frechet-type aryl-ether dendrimers, for nuse in either dendrimer conjugation studies, resin loading enhancement or nthe wedge based synthesis of larger dendrimers.

Combination of Cross-Coupling and Metal Carbene Transformations for the Development of New Multicomponent Reactions

Multicomponent reactions (MCRs) are convergent chemical processes that involve condensation of more than two reactants to form a product, in which basically all or most of the atoms contribute to the newly formed molecule. Usually, MCRs involve the formation of multiple bonds in a single operation without isolating the intermediates or changing the reaction conditions, allowing the straightforward creation of molecular diversity and complexity from simple and readily available substrates. Moreover, the sustainable aspects of MCRs have been recently highlighted: atom economy and step efficiency reduce the number of intermediate steps, functional group manipulations, and use of protecting groups. All these characteristics explain the renewed interest of the synthetic community for MCRs in recent years.

Design of Multi-Component Reactions

Multi-component reactions (MCRs) have now been well established as a powerful synthetic tool for creating molecular complexity and diversity and are undoubtedly well suited for the drug discovery program. Another potential that has probably received less attention among synthetic chemists is the opportunity offered by MCRs for the development of new fundamentally important transformations (reactions). Indeed, although an MCR is composed of a series of known bimolecular reactions, the overall transformation could be novel. Consequently, it provides chemists the opportunities to uncover transformations that were otherwise difficult to realize. In this talk, we will present our recent work in this field, including: (1) the oxidative homologation of aldehydes to amides, (2) the oxidative coupling of aldehydes and isocyanides to α-ketoamides, (3) oxidative isocyanide-based MCRs, and (4) the enantioselective Passerini reaction.