Lipophilic hydroxytyrosyl esters. Antioxidant activity in lipid matrices and biological systems.

Antioxidant activities of lipophilic hydroxytyrosyl acetate, palmitate, oleate, and linoleate were compared with those of hydroxytyrosol, alpha-tocopherol, and butylhydroxytoluene (BHT) in both glyceridic matrix and biological systems. Aliquots of a glyceridic matrix spiked with various concentrations of antioxidant were subjected to accelerated oxidation in a Rancimat apparatus operated at 90 degrees C. The relationships between induction time (IT) and antioxidant concentration (mmol/kg) presented by hydroxytyrosol and hydroxytyrosyl acetate, palmitate, oleate, and linoleate were similar. Hydroxytyrosol and its esters showed greater antioxidant activity than alpha-tocopherol or BHT. We also evaluated the capacity of hydroxytyrosyl esters to protect proteins and lipids against oxidation caused by peroxyl radicals, using a brain homogenate as an ex vivo model. All tested compounds showed a protective effect in these systems, which was greater in preventing the generation of carbonyl groups in protein than of malondialdehyde in lipid. Inclusion of a lipophilic chain in the hydroxytyrosol molecule enhanced its antioxidant capacities in this biological model.

The isopropylsulfinyl group: a useful chiral controller for the asymmetric aziridination of sulfinylimines and the organocatalytic allylation of hydrazones.

[reaction: see text] A comparative study shows that the isopropylsulfinyl group for which an enantiodivergent and highly diastereoselective approach is reported behaves better than the tert-butylsulfinyl and p-tolylsulfinyl groups, both in terms of reactivity and stereoselectivity in the Corey-Chaykovsky reaction of chiral sulfinylimines and the organocatalytic allylation of acyl hydrazones.

Alkylating agents from sugars: synthesis of chlorambucil derivatives carried by chiral glycosyl glycerols derived from D-glucosamine.

Chlorambucilamide derivatives involving chiral glycosyl glycerols derived from D-glucosamine were synthesized in good yield by coupling the chlorambucil moiety to the amino group of omega-amino-(omega-1)-hydroxyalkyl 2-acylamino-4,6-O-benzylidene-2-deoxy-beta-D-glucopyranosides, and subsequent hydrolysis of the benzylidene group. The starting material was easily available from 2-acetamido-2-deoxy-D-glucose. The bonding of 2,3,4,6-tetra-O-pivaloyl-beta-D-galactopyranosylamine to chlorambucil by formation of an amide function is also described.

Dynamic kinetic transformation of sulfinyl chlorides: synthesis of enantiomerically pure C(2)-symmetric bis-sulfoxides.

Two modular and highly convergent approaches for the synthesis of both isomers of a large number of optically pure C(2)-symmetric bis-sulfoxides have been developed, and their scope and limitations have been assessed. The first one uses as intermediate diastereomerically pure C(2)-symmetric bis-sulfinate esters 6(S(S),S(S)) and 6(R(S),R(S)), obtained by dynamic kinetic resolution of ethane-1,2-bis-sulfinyl chloride 5. A single inducer of chirality, the glucose-derived DAG (diacetone-D-glucose) 1 is used for the enantioselective synthesis of both diastereomerically pure C(2)-symmetric bis-sulfinate esters, thanks to the opposite stereodirecting effect of pyridine and (i)Pr(2)NEt used to catalyze the reaction. The second approach is based on the copper-catalyzed oxidative coupling of optically pure lithiomethyl sulfoxides. Both isomers of a large number of methyl sulfoxides can be obtained in a convergent manner using (R(S))- and (S(S))-DAG methanesulfinate esters 8R(S) and 8S(S). Methanesulfinates 8R(S) and 8S(S) are also obtained in an enantioselective way by a dynamic kinetic resolution of methane sulfinyl chloride 24. The final bis-sulfoxides are obtained with enhanced enantioselectivities compared to the corresponding monomers, as a result of the Horeau effect which is operating in both approaches. A model based on the formation of pentacoordinated sulfur intermediate is proposed. This model can explain the dynamic kinetic resolution observed via Berry pseudorotations, without the commonly accepted in situ racemization of the starting material. The usefulness of the approaches is demonstrated by the preparation of complexes of Pd(II) and Ru(II) bearing bidentated chiral sulfoxides as ligands.