Synthesis and Binding Properties of a Tren-Capped Hexahomotrioxacalix[3]arene.

The straightforward synthesis of a new hexahomotrioxacalix[3]arene-based ligand capped by a tren subunit was developed and the binding properties of the corresponding zinc complex were explored by NMR spectroscopy. Similarly to the closely related calix[6]tren-based systems, the homooxacalixarene core ensures the mononuclearity of the zinc complex and the metal center displays a labile coordination site for exogenous guests. However, very different host-guest properties were observed: i) in CDCl3 , the zinc complex strongly binds a water molecule and is reluctant to recognize other neutral guests, ii) in CD3 CN, the exo-coordination of anions prevails. Thus, in strong contrast to the calix[6]tren-based systems, the coordination of neutral guests that thread through the small rim and fill the polyaromatic cavity was not observed. This unique behaviour is likely due to the fact that the 18-membered ethereal macrocycle is too small to let a molecule threading through it. This work illustrates the key role played by the second coordination sphere in the binding properties of metal complexes.

Epoxy Isonitriles, A Unique Class of Antibiotics: Synthesis of Their Metabolites and Biological Investigations.

Epoxy isonitrile containing natural products often possess specific and potent antibacterial activity against Gram-positive pathogens. This scaffold, however, is extremely labile under acidic and basic conditions, undergoing a Payne rearrangement to produce a stable epoxy ketone metabolite and releasing hydrogen cyanide. We synthesized and performed biological assays with epoxy ketone containing metabolites and identified that the epoxy isonitrile moiety is pertinent for biological activity. Serendipitously, we discovered an α,ß-unsaturated epoxy ketone analogue that exhibited moderate activity against Staphylococcus aureus.

Calix[6]azacryptand Ligand with a Sterically Protected Tren-Based Coordination Site for Metal Ions.

A new calix[6]azacryptand ligand has been prepared in six steps starting from 1,3,5-trismethoxycalix[6]arene. An X-ray study shows that this ligand has a sterically protected tren-based binding site at the bottom of a polyaromatic bowl and ether sites around its rim. It binds Zn(2+) to give a complex in which zinc is in a trigonal bipyramidal geometry with a water bound in one apical position and two additional hydrogen-bonded waters that fill the calixarene cavity.

Triflate-functionalized calix[6]arenes as versatile building-blocks: application to the synthesis of an inherently chiral Zn(ii) complex.

Cavity-based metal complexes can find many applications notably in the fields of catalysis and biomimicry. In this context, it was shown that metal complexes of calix[6]arenes bearing three aza-coordinating arms at the small rim provide excellent structural models of the poly-imidazole sites found in the active site of many metallo-enzymes. All these N-donor ligands were synthesized from the 1,3,5-tris-methoxy-p-tBu-calix[6]arene platform, which presents some limitations in terms of functionalization. Therefore, there is a need for the development of new calix[6]arene-based building-blocks selectively protected at the small rim. Herein we describe the regioselective one step synthesis of two calix[6]arenes decorated with triflate groups, i.e. X6H4Tf2 and X6H3Tf3, from the parent calix[6]arene X6H6. It is shown that the triflate groups can either act as protecting or deactivating groups, allowing the elaboration of sophisticated calixarene-based systems selectively functionalized at the large and/or at the small rim. In addition, X6H3Tf3 is functionalized on the A, B, and D rings and thus gives access to inherently chiral compounds, as demonstrated by the synthesis of a rare example of inherently chiral cavity-based metal complex.