Paola Bonaccorsi

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.

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 of D-erythro-sphinganine through serine-derived α-amino epoxides.

A total synthesis of D-erythro-sphinganine [(2S,3R)-2-aminooctadecane-1,3-diol] starting from commercial N-tert-butyloxycarbonyl-L-serine methyl ester is described. The approach is based on the completely stereoselective preparation of an α-amino epoxide obtained by treating a protected L-serinal derivative with dimethylsulfoxonium methylide. The oxirane synthon is obtained with an anti configuration fitting the (2S,3R) stereochemistry of the 2-amino-1,3-diol polar head of D-erythro-sphinganine. The synthetic procedure afforded the target compound in a 68% overall yield based on the initial amount of the starting L-serine material.

Deprotection/reprotection of the amino group in α-amino acids and peptides. A one-pot procedure in [Bmim][BF4] ionic liquid

This paper presents an efficient one-pot protocol for the sequential deprotection/reprotection of the α-amino group in α-amino acid and dipeptide methyl esters. [Bmim][BF4] is used as the solvent in the entire process. In particular, the use of the ionic liquid allows for rapid and clean removal of the 4-nitrobenzenesulfonyl (nosyl) group and for facile subsequent tert-butyloxycarbonylation of the free α-amino function under very mild conditions. N-Boc-α-amino acid as well as peptide derivatives are isolated in excellent yields, and do not require any further purification. Absolute configurations of the precursors are totally preserved during the process.

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.

Intramolecular displacement of phenylselenone by a hydroxy group: stereoselective synthesis of 2-substituted tetrahydrofurans.

An efficient and stereocontrolled synthesis of 2-substituted tetrahydrofurans has been achieved. The approach employs the asymmetric reduction of γ-phenylseleno ketones obtained by three different procedures that are peculiarly applied to the synthesis of such compounds. Finally, the intramolecular substitution of the phenylselenone residue by the oxygen atom of a hydroxy group gives the tetrahydrofuran ring.

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.