Digitalis cardiac glycosides are well known drugs clinically used for treatment of congestive heart failure.1 Their action is mainly due to inhibition of Na+,K+-ATPase, an enzyme located in the cell membrane and promoting the outward transport of Na+ and the inward transport of K+.2 Recently the existence of endogenous digitalis-like factors that may be responsible for essential hypertension3 has opened a new field in the study of compounds acting on the Na+,K+-ATPase. The most potent inhibitors of Na+,K+-ATPase are cardenolides such as digitoxigenin (Figure 1) with the following structural characteristics: 17b-unsaturated lactone, 3b- and 14b-hydroxy substituents and A/B and C/D cis ring junctions. The 14b-hydroxy group is involved in a hydrogen bonding with the receptor and plays an important role in binding digitalis compounds to Na+,K+-ATPase receptor; in fact compounds in which this group is absent show very low binding affinity or no affinity at all.4 However the known derivatives with a 14b,15b-epoxy group (Figure 1) show high binding affinities although not as high as the 14b-hydroxy analogues

Digitalis cardiac glycosides are well known drugs clinically used for treatment of congestive heart failure.1 Their action is mainly due to inhibition of Na+,K+-ATPase, an enzyme located in the cell membrane and promoting the outward transport of Na+ and the inward transport of K+.2 The most potent inhibitors of Na+,K+-ATPase are cardenolides such as digoxin, digitoxin, digitoxigenin and gomphoside (Figure 1). The first three compounds have some common features, typical of digitalis: 17b-unsaturated lactone; 14b-hydroxy; A/B and C/D cis ring junctions; 3b-hydroxy or 3b-glycosyl linkage with digitoxose. A quite different molecule is gomphoside, an A/B trans cardiac glycoside from Asclepias fruticosa RBr,3 in which the aglycone (gomphogenin) is linked to a 4,6-dideoxyhexosulose trhough its 2a- and 3b-hydroxy groups.

4-Aryldihydropyrimidines (DHPMs) represent inherently chiral aza-analogs of nifedipine-type dihydropyridine (DHP) calcium channel modulators. In the context of the recently proposed new binding-site model for these types of cardiovascular drugs, conformationally rigid DHPM analogs were designed that closely mimic the receptor-bound conformation of DHP/DHPM calcium channel modulators. The synthetic methodology towards these pentacyclic DHPM analogs is based on intramolecular 1,3-dipolar cycloaddition reactions of o-alkenylaryl-tethered dihydropyrimidine-fused isomünchnones. Two homologs of these rigid DHPM derivatives were synthesized in good overall yield and their structure established by X-ray crystallographic analysis. Enantioseparation of these DHPMs was achieved by chiral HPLC.

We have recently reported the synthesis of enantiopure 3-heterosubstituted pyrroline N-oxides of type 1 and 2 (Scheme 1) obtained by oxidation of the corresponding hydroxylamines, in turn available in large amounts from L-malic and L-aspartic acids, respectively.1

A new general convenient approach to the synthesis of pyrimidine-2-thiones/ones has been developed. This approach is based on the preparation of a-tosyl and a-azido substituted thioureas and ureas followed by the reaction with sodium enolates of carbonyl compounds.

Some general methods for carbon-heteroatom, carbon-hydrogen and carbon-carbon bond formation at the 4 position of hexahydropyrimidine-2-thiones/ones based on the usage of ureidoalkylation have been developed.

The 2-oxetanone (beta.lactone) ring is present in several natural biologically active compounds. The use of chiral (eta6) tricarbonylchromium derivatives for the stereoselective synthesis of small ring heterocycles is already well documented.1-4 Among the different methods for preparing b-lactons, we envisage the lactonization "via" b-hydroxy carboxylic acids as promising approch to this class of compounds starting from optically pure substituted chromium tricarbonyl benzaldehydes. Following the procedure reported in the scheme, a series of enantiomerically pure b-lactones have been obtained. One example is reported in this Poster.

Intramolecular 1,3-dipolar cycloadditions represent a valuable tool in the synthesis of a large variety of heterocyclic systems containing a five- membered heterocycle fused or bridged to another hetero- or carbo-cyclic ring.1 However, despite to the usefulness of this methodology, the examples in which is implied the formation of a medium-sized ring are still rare.2,3

The preparation, spectroscopic characterisation and biological activity 2-(6-acetamido-benzolethio)acetic acid esters are reported in this communication.

Differential Scanning Calorimetry (DSC) has been shown to provide useful information in organic synthesis in the stage of planning thermolytical reactions [1]. This information can be obtained before the reaction itself is performed and include the temperature range of the planned reaction, hints on subsequent rearrangement and decomposition reactions, choice of suitable solvents and safety precautions in exothermic processes.