Transient Sulfenic Acids in the Synthesis of Biologically Relevant Products.

Sulfenic acids as small molecules are too unstable to be isolated and their transient nature offers the possibility to involve them in concerted processes that lead to the obtainment of functional groups such as sulfoxides, sulfones, and disulfides. All these functions are present in a number of natural and synthetic drugs and can represent structural motives inducing biologically relevant properties. In this small review the generation and reactions of sulfenic acid bearing naturally occurring residues are described. Carbohydrate and aminoacid-derived sulfenic acids have been used in concerted addition with triple bonds to obtain alliin derivatives and thiosugars in enantiomerically pure form. Glycoconjugates with sulfinyl, sulfonyl, and disulfane functional groups and pyridine-derived disulfides have been obtained from bis- and tris-sulfinyl precursors of sulfenic acids. Small families of such compounds have been subjected to preliminary biological tests. Starting from the evidence that the control of molecular architecture and the presence of suitable functional groups can play a significant role on the exhibition of biological properties, apoptotic effects on malignant cells by glycoconjugates and inhibitory activity against the important human pathogen S. aureus by pyrimidine-derived disulfides have been found.

Artificial light-harvesting antenna systems grafted on a carbohydrate platform.

An enantiopure α-D-glucopyranoside derivative has been used as a platform to prepare artificial antenna systems based on bodipy subunits. Efficient and ultrafast energy transfer (in the fs and ps time regimes) takes place in the multibodipy systems.

Thiacyclophane cages and related bi- and tripodal molecules via transient polysulfenic acids.

A series of bis- and tris-bridged thiacyclophane S-oxides, as racemates or meso products, have been synthesized with a new procedure. Starting from the corresponding thiols, in three steps, transient polyarene- and polyarylmethane-sulfenic acids were generated in the presence of di- and triethynylbenzenes. The thermal syn-addition of these sulfenic acids onto the triple bonds of the unsaturated acceptors was conducted in CH2Cl2 at 40 degrees C. The concentration of sulfoxide precursors of sulfenic acid and the sulfoxide/acceptor molar ratio addressed the syn-addition toward open-chain benzene sulfoxides or thiacyclophane S-oxides. Complete stereochemical control was observed in some reactions between polysulfenic acids and ethynylbenzenes, where the meso dithiacyclophane S,S'-dioxides were obtained exclusively, whereas 1:1 mixtures of meso/rac dithiacyclophanes S,S'-dioxides were isolated as products of other reactions. In almost all the cases, the obtained compounds were separated by column chromatography. The structure assignment of the new heterophanes was done on the basis of their diagnostic NMR spectra and X-ray crystallographic analysis of some of them. Open-chain polysulfinyl and polysulfinylmethyl benzenes, obtained as meso/rac mixtures, were separated and the products were fully characterized. Both synthesized cages, including trithia[3(3)](1,3,5)cyclophane S,S',S' '-trioxides, and bi- and tripodal benzene sulfoxides, appear promising in the field of coordination and material chemistry.

Synthesis and "double-faced" antioxidant activity of polyhydroxylated 4-thiaflavans.

A simple synthetic methodology, based on the inverse electron demand hetero Diels-Alder reaction of electron-poor dienic o-thioquinones with electron-rich styrenes used as dienophiles, allowed the preparation of several polyhydroxylated 4-thiaflavans. Such compounds, as a function of the nature and position of the substituents on the aromatic rings, as well as of the oxidation state of the sulfur atom, are able to behave in vitro as efficient antioxidants mimicking the action of catechol containing flavonoids or/and tocopherols. The possibility of joining together the potentialities of two relevant families of natural polyphenolic antioxidants appears particularly appealing since an efficient protection against free radicals and other reactive oxygen species (ROS) depends in vivo upon the synergic action of different antioxidant derivatives.