Augusto Gambacorta

Noncovalent Organocatalysis: A Powerful Tool for the Nucleophilic Epoxidation of α-Ylideneoxindoles

A novel asymmetric nucleophilic epoxidation for α-ylideneoxindole esters has been successfully devised, resulting in enantioenriched spiro compounds with two new contiguous stereocenters. The employed (S)-α,α-diphenylprolinol functions as a bifunctional catalyst, creating a complex H-bond network in conjunction with a substrate and an oxidant.

Fatty acid hydroxytyrosyl esters: structure/antioxidant activity relationship by ABTS and in cell-culture DCF assays.

A large series of hydroxytyrosyl esters of C2-C18 fatty acids with increasing lipophilicity was prepared by a new highly efficient method based on acylation of methylorthoformate-protected hydroxytyrosol. All products were tested for relative antioxidant effect using ABTS assays in ethanolic medium and DCF assays in L6 cells. No linear correlation between lipophilicity and antioxidant effect was found. ABTS assays showed a growing antioxidant capacity, with respect to hydroxytyrosol, only for medium-sized ester chains (C4-C10) and a nearly constant capacity for the higher homologues. This has been rationalized by molecular dynamics experiments in terms of partial shielding of the catecholic hydroxyls by long-chain esters. A similar and dose-dependent pattern was observed in DCF assays in L6 cells, but a sharp antioxidant activity drop resulted for long-chain esters, probably due to membrane entrapment.

Synthesis and Structure/Antioxidant Activity Relationship of Novel Catecholic Antioxidant Structural Analogues to Hydroxytyrosol and Its Lipophilic Esters

A large panel of novel catecholic antioxidants and their fatty acid or methyl carbonate esters has been synthesized in satisfactory to good yields through a 2-iodoxybenzoic acid (IBX)-mediated aromatic hydroxylation as the key step. The new catechols are structural analogues of naturally occurring hydroxytyrosol (3,4-DHE). To evaluate structure/activity relationships, the antioxidant properties of all catecholic compounds were evaluated in vitro by ABTS assay and on whole cells by DCF fluorometric assay and compared with that of the corresponding already known hydroxytyrosyl derivatives. Results outline that all of the new catechols show antioxidant capacity in vitro higher than that of the corresponding hydroxytyrosyl derivatives. Less evident positive effects have been detected in whole cells experiments. Cytotoxicity experiments, using MTT assay, on a representative set of compounds evidenced no influence in cell survival.

6-Alkyl- and 5,6-Dialkyl-2-methoxy-4(3H)-pyrimidinones in the Transformations of Pyrimidines. Conversion into 2-Substituted Amino- and 4-Chloro-Pyrimidine-Derivatives

Abstract 6-Alkyl- and 5,6-dialkyl-2-methoxy-4(3H)-pyrimidinones are transformed into the 2-alkyl(and 2-aryl)amino-derivatives, in good yield, by reaction with the corresponding amines. Treatment with SOCl2 -DMF gives 6-alkyl- and 5,6-dialkyl-2-methoxy-4-chloro pyrimidines.

A highly regio- and stereoselective C5 oxyfunctionalization of coprostane steroids by dioxiranes: An improved access to progestogen and androgen hormones.

Abstract Coprostane steroids are selectively oxyfunctionalized at C 5 by dimethyldioxirane and methyltrifluoromethyldioxirane to give useful intermediates for bioactive compounds.

HSAB Driven chemoselectivity in alkylation of uracil derivatives. A high yielding preparation of 3-alkylated and unsymmetrically 1,3-dialkylated uracils

Abstract A qualitative hardness scale (N 1 3 4 ) has been found for the conjugated bases of 2-methoxy-4(3H)-pyrimidinones 1–3 and applied to high yielding chemoselective N 3 methylation, ethylation and benzylation reactions. Removal of the 2-methoxy group followed by a second alkylation affords unsymmetrically 1,3-disubstituted uracils.

Bicyclo [3.3.1] nonane approach to pinguisane terpenoids: total synthesis of (+) pinguisone

Abstract The total synthesis of (±) pinguisone 1, the sterically crowded unusual [5-6] fused-ring sesquiterpene, was accomplished by synthetic elaboration of the 3β,3aβ,7,7aβ-tetramethylbicyclo [4.3.0] non-6-en-1-one 2a prepared by acid catalyzed rearrangement of the easily accessible 1,4β,5,9-tetramethylbicyclo [3.3.1] nonan-9-hydroxy-2-one 3 . This rearrangement constitutes an example of the scarcely observed 1,2 shift of a carbonyl group toward an electron deficient centre.

Desymmetrisation of meso-methylcyclooctanones. Highly enantioselective synthesis of C8 syn-isoprenoid and syn, syn-deoxypropionate subunits from a bicyclo[3.3.1]nonane precursor

Abstract The methyl esters of 3 R ,7 S -dimethyl- and 3 R ,5 R ,7 S -trimethyl-8-hydroxyoctanoic acids have been prepared in good yields and with e.e. >98% by chemical elaboration of the known exo , exo -3,7-dimethylbicyclo[3.3.1]nonan-9-one, the key step involving the desymmetrisation of the intermediate meso -ketones cis -3,7-dimethyl- and cis , cis -3,5,7-trimethyl-cyclooctanone through the corresponding chiral enolates generated by the lithium amide of the (+)bis[( R )-(1-phenylethylamine)]. The very high enantioselectivity observed might be related to the conformational features of the eight-membered ring.

Bicyclo[3.3.1]nonane approach to triquinanes. Formal synthesis of (+/-)Δ9(12) capnellen and (+/-)Δ9(12) capnellen-8β-10α-diol

Abstract A new synthetic strategy for natural triquinanes is presented as a model study. Stereospecific rearrangement of the ready accessible bicyclo[3.3.1] nonanic acetoxychloride 6 gave the cis -pentalamic hydroxyaldehyde 5 , which has been converted into the ketone 4 already reported as a key intermediate in some syntheses of the title capnellenes.

A novel ring enlargement: The cyclic expansion of 2-dichloromethyl-2h-pyrroles☆

Abstract Substituted 2-dichloromethyl-2H-pyrroles, when treated with strong bases under appropriate conditions, undergo ring enlargement giving substituted 3-chloropyridines. The data collected on different substrates and reagents indicate the carbenoid nature of intermediate.