D(-)lentiginosine-induced apoptosis involves the intrinsic pathway and is p53-independent.

We have recently found that D(-)lentiginosine, a synthetic iminosugar exerting glucosidase inhibitory activity, but not its natural enantiomer lentiginosine, is endowed with an unexpected, pro-apoptotic activity. Here, we investigated mechanisms involved in apoptosis induced by D(-)lentiginosine in MOLT-3, HT-29 and SH-SY5Y tumour cell lines. The results showed that D(-)lentiginosine increased caspase 9 expression at 18 h in all the cell lines from 1.5-3.1 folds. Cytochrome c in the cytoplasm was found to be increased from 2.3-2.6 folds in treated cells with respect to control cells. These effects were accompanied by a remarkable collapse of the mitochondrial membrane potential and by the downregulation of anti-apoptotic genes, as well as the upregulation of pro-apoptotic genes of the Bcl-2 family. U937Bcl-2 transfectants, highly expressing Bcl-2, were reluctant to undergo apoptosis even following treatment with 500 µM D(-)lentiginosine, whereas apoptosis by D(-)lentiginosine was induced also in U937 cells, naturally deficient in P53. Thus, our study establishes that the enantiomer of a natural iminosugar is endowed with a possible anti-tumorigenic effect that might be ascribed not only to their capacity to inhibit glycosidases but also to other unknown mechanisms. These data encourage further investigation on similar compounds to make them an interesting platform for the generation of new anticancer drugs.

Total synthesis of (-)-rosmarinecine by intramolecular cycloaddition of (S)-malic acid derived pyrroline N-oxide.

[reaction in text] Straightforward total syntheses of (-)-rosmarinecine have been achieved from L-malic acid derived pyrroline N-oxides by two novel useful cascade processes, which join the family of domino reactions. Both strategies, which furnished the target alkaloid in enantioenriched and enantiopure forms, respectively, allow complete control of configuration at all the three newly created contiguous stereogenic centers.

Design and synthesis of a new bicyclic dipeptide isostere.

The synthesis of a new Gly-Pro turn mimetic and the computational study of its ability to induce beta-turn is reported.

Stereoselective approach to hydroxyindolizidines: protection/deprotection of the nitrone functionality via cycloaddition/retrocycloaddition.

The enantiomerically pure indolizidine (-)-21 has been synthesized starting from L-malic acid. The key intermediate 20 has been assembled through an intramolecular 1,3-dipolar cycloaddition of a nitrone generated in situ by retrocycloaddition from isoxazolidine 17 or 18. The configuration of the new three stereocenters was set up with complete control in the cycloaddition step. The presented synthetic route provides a general and highly selective methodology toward indolizidines having the [1,8a]-cis configuration.

Regio- and stereoselective cycloadditions of cyclic nitrones to maleic diamide forced in a peptide: synthesis of potent ligands of human NK-2 receptor.

The regioselectivity and the stereoselectivity induced by relatively small peptidomimetic maleic diamide 1 in cycloaddition reactions with cyclic nitrones 2-5 was studied. The high regio- and stereoselectivity observed, sensibly increased by nonpolar solvents, was the effect of a double-asymmetric induction produced by the nitrone substituent on the pseudopeptidic tether. A new class of potent human tachykinin NK-2 receptor ligands was synthesized.

Synthesis of taurine analogues from alkenes: preparation of 2-aminocycloalkanesulfonic acids.

(+/-)trans 2-Aminocyclohexanesulfonic acid and (+/-)trans 2-aminocyclopentanesulfonic acid were prepared from cyclohexene and cyclopentene respectively by sulfur monochloride addition, followed by oxidation to 2-chlorosulfonic acid and substitution of chlorine.