Carina M. L. Delpiccolo

Stereoselective solid-phase synthesis of 3,4-substituted azetidinones as key intermediates for mono- and multicyclic β-lactam antibiotics and enzyme inhibitors

The polymer-supported Staudinger reaction proceeded smoothly under mild conditions to give the corresponding β-lactams in good to high overall yields with excellent cis-selectivity. Upon applying this reaction system, an efficient asymmetric synthesis of β-lactams was accomplished, when chiral acid chlorides or chiral aldehydes were used. These optically active β-lactams would be useful precursors for the generation of combinatorial libraries of potential antibiotics and enzyme inhibitors.

Solid-phase synthesis of 2β-methyl substituted penam derivatives through penicillin sulfoxide rearrangement

Abstract A new, robust protocol for the solid-phase synthesis of 2β-methyl substituted penam derivatives is described. This synthetic sequence works reliably in good to high overall yields using Merrifield resin as support. The key step involves the thermal rearrangement of the corresponding penicillin sulfoxide.

Very efficient and broad-in-scope palladium-catalyzed Hiyama cross-coupling. The role of water and copper(I) salts

A very high-yielding Pd-catalyzed cross-coupling between aryl halides and aryl(trialkoxy)silanes is achieved in the presence of Cu(I) and a measured amount of water. This novel methodology is useful for the generation of a wide range of biaryls, particularly non-para substituted derivatives, which are usually less reported.

Chemoselective and Sequential Palladium-Catalyzed Couplings for the Generation of Stilbene Libraries via Immobilized Substrates

A versatile palladium-catalyzed tandem synthetic sequence to afford E-stilbenes libraries has been developed. Excellent regio- and stereocontrol have been achieved by means of the sequence of Hiyama and Heck cross-couplings. Undesirable homocoupling byproducts were avoided employing immobilized substrates.

In vitro anticancer activity and SAR studies of triazolyl aminoacyl(peptidyl) penicillins

A library of triazolyl aminoacyl(peptidyl) penicillins was designed, synthesized, and evaluated for their antiproliferative activity against HeLa and B16-F0 cell lines. Structure–activity relationship studies were carried out, and minimal structural requirements were determined. Among the tested compounds, derivatives 7f, 7p and 7m demonstrated the highest anticancer activity and a promising selectivity profile against these two cell lines.

Immobilized boronic acid for Suzuki–Miyaura coupling: application to the generation of pharmacologically relevant molecules

An synthetic strategy for the generation of a variety of biaryl and related derivatives, based on Suzuki–Miyaura coupling using immobilized boronic acid, is described. The importance of the methodology was demonstrated by its further application to biologically interesting compounds such as 4-biaryl-β-lactams, descripted as cholesterol absorption inhibitors and anti-MRSA active agents, neoflavonoids, imidazoles, isoxazolines, among others.

Recent Approaches Toward the Generation of Molecular Diversity Based on β-Lactam Structures

One of the most significant strategies in the search of biologically promising structures is the generation of scaffold diversity. Varying molecular scaffolds yielded useful small molecule tools for chemical genetic studies of cellular protein functions, apart from “classic” drug discovery approaches. In this chapter, the latest developments for the transformation of β-lactam monocyclic moieties into complex and diverse structures are discussed. The significance of the 2-azetidinones as starting material for the synthesis of libraries of fused and non-fused multicyclic β-lactams, multicyclic (non-β-lactamic) scaffolds, as well as new heterocyclic derivatives of pyrroles, γ-lactones, γ-lactams, oxazinones, imidazolidines, piperazines, piperidines, among others. Finally, the importance of β-lactam-based hybrids as a new source of potential biologically active compounds, have been also highlighted.

Design of a Selective Ring-Closing Enyne Metathesis–Reduction for the Generation of Different Synthetic Scaffolds

A tandem process of ring-closing enyne metathesis (RCEYM)-reduction using modern ruthenium catalysts and a hydrogen donor is described. This straightforward methodology is useful for C(sp3) generation under mild reaction conditions. Variables such as solvent, catalyst, hydride source, and temperature were adjusted toward the exclusive formation of different products.

Advances in Metal-Mediated Solid-Phase Synthesis of Heterocyclic Compounds

While heterocycles are a key feature frequently found in compounds with pharmaceutical or agrochemical interest, the combination between solid-supported synthesis and organometallic chemistry has demonstrated to be a helpful tool for the preparation of that class of biologically relevant structures. From the more disclosed Huisgen 1,3-dipolar cycloaddition, the palladium-catalyzed synthesis of indoles and the ruthenium carbene-mediated preparation of heterocycles by ring-closing metathesis (RCM), to the less developed use of gold and iron in polymer-supported chemistry, this survey offers an overview of the solid-phase application of metal-mediated chemistry to the generation of libraries of a variety of heterocyclic systems.