Synthesis and Reactivity of Oligo(ethylene glycol)-Tethered Morita-Baylis-Hillman Dimers in the Formation of Macrocyclic Structures Showing Remarkable Cytotoxicity.

: Crown ethers have received increasing interest owing to their ability to form stable complexes with cations. This molecular feature has been successfully exploited in the development of biologically relevant ionophores. : In order to obtain innovative crown ethers derivatives, a Morita-Baylis-Hillman adduct (MBHA) acetate () bearing a phenylacetylene moiety was dimerized via the click-chemistry CuAAC reaction with oligo(ethylene glycol) diazide derivatives to build-up a small series of dimeric MBHA derivatives (). These dimeric MBHA derivatives were reacted with n-butylamine to afford tunable macrocyclic crown ether-paracyclophane hybrid architectures (). : Compounds (,)-, (,)-, showed, in human breast cancer MDA-MB-231 and human melanoma A375 cells, IC values comparable with those of reference anticancer agent Doxorubicin. : This exploration approach provides original new macrocyclic architectures potentially useful as anticancer agents.