Maria C. Aversa

Control of stereochemistry by sulfoxide chirality in Diels-Alder reactions of 1-methoxy-3-alkylsulfinylbutadienes

Abstract Cycloadditions of methyl acrylate to (R S )- and (S S )-(E)-3-[(1S)-isobornyl-10-sulfinyl]-1-methoxy-buta-1,3-dienes in dichloromethane, catalysed by lithium perchlorate or zinc chloride, proceeded with complete regioselectivity and high stereoselectivity. Chirality at sulfur controlled diastereofacial selectivity.

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.

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.

Homochiral 1-methoxy-3-sulfinyl-1,3-butadienes derived from 10-mercaptoisoborneol

Abstract Simple syntheses of homochiral (Z)- and (E)-1-methoxy-3-alkylsulfinyl-1,3-butadienes were provided by the cycloaddition of (1S)-d-isobornyl-10-sulfenic acid to (Z)- and (E)-1-methoxybut-1-en-3-yne. Asymmetric induction pertained for such cycloadditions, which also provided homochiral dienes from 1-ethynylcyclohex-1-ene.

Synthesis and biological evaluation of a new class of glycoconjugated disulfides that exhibit potential anticancer properties.

A synthetic strategy, based on the in situ generation of sulfenic acids and their thermolysis in the presence of thiols, was developed for obtaining a collection of polyvalent disulfides in which a benzene scaffold accommodates two or three flexible arms connecting saccharide moieties. Targeting carbohydrate metabolism or carbohydrate-binding proteins may constitute important approaches in the discovery process of new therapeutic anticancer agents. Therefore, a preliminary screening to ascertain the cytostatic/cytotoxic potential of this new class of enantiopure glycoconjugated disulfides has been conducted. Among them, products with two disulfide arms, harbouring galactose rings, induced high levels of apoptosis on U937 histiocytic lymphoma cells, but lower levels of cell death on peripheral blood mononuclear cells from healthy donors. Further experiments indicated that apoptosis induced by these glycoconjugated bis(disulfides) in U937 cells corresponds to the Bcl-2-sensitive, intrinsic form of apoptotic cell death. The bioinvestigation was extended to a panel of human cancer cell lines with different levels of malignancy and resistance to chemotherapeutic agents. Compounds under study proved to induce detectable levels of cell death towards all the tested cancer cell lines.

Asymmetric Diels-Alder reactions of enantiopure 1-methoxy-3-(phenyl-2-hydroxyethylsulfinyl)-1,3-butadienes

Abstract Enantiopure 1-methoxy-3-(1-phenyl- and 2-phenyl-2-hydroxyethylsulfinyl)-1,3-butadienes were prepared from ethyl mandelate. Diels-Alder reactions with methyl acrylate proceeded with complete regioselectivity and high diastereoselectivity.

Synthesis and biological testing of thioalkane- and thioarene-spaced bis-β-d-glucopyranosides

A three-step synthesis of bis-beta-D-glucopyranosides containing thioalkane or thioarene spacers of different length and flexibility is described. The key-step reaction allows an easy modulation of final saccharidic products so that a library of molecules with different glycosidic residues and spacers can be obtained. Two of the new thioarene-spaced bis-beta-D-glucopyranosides endow with a specific cytotoxic potential. A more detailed investigation of one of the two compounds ascertains that this effect is attributable to induction of cell death by apoptosis.

Diels–Alder reactions of enantiopure [(1S)-isoborneol-10-sulfinyl]- and [(1S-exo)-2-bornylsulfinyl]vinylcyclohexenes with maleimides

Abstract Uncatalyzed cycloadditions of enantiopure [(1 S )-isoborneol-10-sulfinyl]- and [(1 S - exo )-2-bornylsulfinyl]vinylcyclohexenes with N -phenylmaleimide occur with good facial diastereoselectivity, controlled by the sulfur configuration, even if the extent of this stereoselection appears influenced by the structural features of the terpene residue directly linked to the sulfoxide moiety. Complete endo diastereoselectivity is observed in LiClO 4 catalyzed cycloadditions of ( R S )-1-{1-[(1 S )-isoborneol-10-sulfinyl]- and ( S S )-1-{1-[(1 S-exo )-2-bornylsulfinyl]vinyl}cyclohexenes 4 and 5 , respectively. The Diels–Alder reactivity of 5 and ( S S , E )-1-{2-[(1 S-exo )-2-bornylsulfinyl]vinyl}cyclohexene 7 , with the chiral auxiliary being in a different position with respect to the diene moiety, is also compared, and the results obtained comfirm that 1-sulfinyldienes are less reactive than 2-sulfinyldienes. SnCl 4 catalyzed cycloaddition of 7 with N -methylmaleimide is also performed.

Diels–Alder reactions of (RS)-3-[(1S)-isoborneol-10-sulfinyl]-1-methoxybuta-1,3-dienes with electron-deficient carbodienophiles. The effects of Lewis acid catalysis

Abstract Uncatalyzed cycloadditions of (RS,E)-1 and (RS,Z)-3-[(1S)-isoborneol-10-sulfinyl]-1-methoxybuta-1,3-diene 2 with maleimide and N-phenylmaleimide occurred with complete endo and very high facial diastereoselectivities. The effects of Lewis acid catalysis on these Diels–Alder reactions have been evaluated. LiClO4 catalyzed cycloaddition of 1 with dimethyl maleate gave cyclohexene 13 as the unique product with complete control of endo and π-facial diastereoselectivities exerted by the sulfinyl group. A significant improvement in diastereoselectivity was also observed in the LiClO4 catalyzed cycloaddition of 1 with dimethyl fumarate.

Enantiopure 2-sulfinylbuta-1,3-dienes in Diels–Alder cycloadditions: a stereoselective approach to an azasteroidal skeleton

Abstract The synthesis of enantiopure 4-[1-(alkylsulfinyl)vinyl]-1,2-dihydronaphthalenes and their Diels–Alder reactions are described. Cycloadditions with N -phenylmaleimide occur under thermal conditions, very slowly but with notable stereoselection, giving in each case just one of the two endo adducts in high yield. The obtained 16-azasteroid derivatives undergo chiral auxiliary removal in the presence of TMSI.