Synthesis of four iminosugars fused to a cyclopropane ring is described using L-serine as the chiral pool. The key steps are large-scale preparation of an α,β-unsaturated piperidinone followed by completely stereoselective sulfur ylide cyclopropanation. Stereochemistry of compounds has been studied by nuclear Overhauser effect spectroscopy (NOESY) experiments and 1 H homonuclear decoupling to measure constant couplings. The activity of these compounds against different glycosidases has been evaluated. Although inhibition activity was low (compound 8a presents a (K i ) of 1.18 mM against βgalactosidase from Escherichia coli), interestingly, we found that compounds 8a and 8b increase the activity of neuraminidase from Vibrio cholerae up to 100%.

Ene-cyclopropenes give functionalized indanes and tetralines in the presence of ruthenium dimeric catalysts. This reaction involves the cyclopropene opening by the metal catalysts with a different regioselectivity respective to gold chlorides and produces totally different products than when using semisandwich ruthenium complexes. Here, the process leads to a bridged 7-oxanorbornene-type intermediate that is converted into a functionalized aromatic ring through deoxygenative aromatization. Alternative reaction pathways occur with substrates with no possible aromatization.

A one pot alkenylation followed by a stereoselective Alder-ene cycloisomerization of cyclopropenes give (aza)­spiro[2.4]­heptanes and spiro[2.5]­octanes in high yields. Total trans diastereoselectivity is achieved for spiro[2.4]­heptanes if the cyclopropene is monosubstituted in C3. When an α,β-unsaturatedcarbonyl-containing bromide is used, an alternative cyclization takes place giving cyclopenta­[c]­cyclopropa­[b]­pyrans.

Cyclopropanated iminosugars have a locked conformation that may enhance the inhibitory activity and selectivity against different glycosidases. We show the synthesis of new cyclopropane-containing piperidines bearing five stereogenic centers from natural amino acids l-serine and l-alanine. Those prepared from the latter amino acid may mimic l-fucose, a natural-occurring monosaccharide involved in many molecular recognition events. Final compounds prepared from l-serine bear S configurations on the C5 position. The synthesis involved a stereoselective cyclopropanation reaction of an α,β-unsaturated piperidone, which was prepared through a ring-closing metathesis. The final compounds were tested as possible inhibitors of different glycosidases. The results, although, in general, with low inhibition activity, showed selectivity, depending on the compound and enzyme, and in some cases, an unexpected activity enhancement was observed.