María José Arévalo

Multicomponent Reactions for de Novo Synthesis of BODIPY Probes: In Vivo Imaging of Phagocytic Macrophages

Multicomponent reactions are excellent tools to generate complex structures with broad chemical diversity and fluorescent properties. Herein we describe the adaptation of the fluorescent BODIPY scaffold to multicomponent reaction chemistry with the synthesis of BODIPY adducts with high fluorescence quantum yields and good cell permeability. From this library we identified one BODIPY derivative (PhagoGreen) as a low-pH sensing fluorescent probe that enabled imaging of phagosomal acidification in activated macrophages. The fluorescence emission of PhagoGreen was proportional to the degree of activation of macrophages and could be specifically blocked by bafilomycin A, an inhibitor of phagosomal acidification. PhagoGreen does not impair the normal functions of macrophages and can be used to image phagocytic macrophages in vivo.

3+2 -cycloadditions of 2-aminothioisomunchnones to alkynes: Synthetic scope and mechanistic insights

Abstract This manuscript describes the regiospecific 1,3-dipolar cycloadditions of 2-aminothioisomunchnones (1–3) with methyl propiolate. The structure of compound 4 has been unequivocally determined by X-ray crystallography. Based on these experimental arguments and a theoretical rationale that supports the regiochemistry observed, a mechanistic pathway is discussed to account for the formation of pyridone or thiophene derivatives. The protocol has also been extended to the cycloadditions of aminothioisomunchnones derived from carbohydrates with dimethyl acetylenedicarboxylate to afford interesting glycosylaminoheterocycles.

Expeditious formation of 1,2,4-triazine derivatives via a thiosomünchnone cycloaddition reaction

A novel type of heterocyclization reaction involving the [3+2] cycloaddition of N,N-dialkylamino-substituted thioisomunchnones with azodicarboxylates gives rise to 1,2,4-triazine derivatives after a selective fragmentation pathway of the transient cycloadducts. The X-ray analysis of 7 accounts for the fate of this particular transformation. An asymmetric version using chiral carbohydrate-based thioisomunchnones has also been disclosed.

Optically active sugar thioamides from δ-gluconolactone

Abstract This paper describes a facile and rapid approach to N -alkyl- and N -aryl-thiogluconamides employing δ-gluconolactone as starting material. The protocol involves a three-step sequence to afford the corresponding thioamides as crystalline substances in moderate to good yields. The Lawesson reagent was found to be the reagent of choice to accomplish the key transformation amide–thioamide.

Generation and fate of a novel homochiral mesoionic dipole: synthesis of C-nucleoside analogs

Abstract A mesoionic acyclic C-nucleoside 4, generated readily from δ-gluconolactone in a few synthetic steps, serves as the chiral core to construct a series of functionalized nucleosides bearing 2-aza-7-thiabicycle[2.2.1]heptane or 2-(1H)-pyridone moieties as the aglycon. The key step involves a [3+2] cycloaddition of 4 with several olefinic dipolarophiles followed by hydrogen sulfide elimination with mercury(II) acetate.

Facile Synthesis of 4,5-Dihydro-1,3,4-Thiadiazoles by 1,3-Dipolar Cycloaddition of Thioisomünchnones

The present paper summarizes a straightforward synthesis of 4,5-dihydro-1,3,4-thiadiazoles by the 1,3-dipolar cycloaddition of thioisomunchnones. These reactions have been carried out in dichloromethane and are essentially complete within 60 min at room temperature. Under such mild conditions the asymmetric version has been explored as well. Unequivocal structure elucidation has been accomplished by means of one- and two-dimensional NMR techniques as well as X-ray structure analysis.

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.