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In recent years, meroterpenoids have found wide biomedical application due to their synthetic availability, low toxicity, and biocompatibility. However, these compounds are not used in targeted drug delivery systems due to their high affinity for cell membranes, both healthy and in cancer cells. Using the approach of creating supramolecular amphiphiles, we have developed self-assembling systems based on water-soluble pillar[5]arene and synthetic meroterpenoids containing geraniol, myrtenol, farnesol, and phytol fragments. The resulting systems can be used as universal drug delivery systems. It was shown by turbidimetry that the obtained pillar[5]arene/synthetic meroterpenoid systems do not interact with the model cell membrane at pH = 7.4, but the associates are destroyed at pH = 4.1. In this case, the synthetic meroterpenoid is incorporated into the lipid bilayer of the model membrane. The characteristics of supramolecular self-assembly, association constants and stoichiometry of the most stable pillar[5]arene/synthetic meroterpenoid complexes were established by UV-vis spectroscopy and dynamic light scattering (DLS). It was shown that supramolecular amphiphiles based on pillar[5]arene/synthetic meroterpenoid systems form monodisperse associates in a wide range of concentrations. The inclusion of the antitumor drug 5-fluoro-2′-deoxyuridine (floxuridine) into the structure of the supramolecular associate was demonstrated by DLS, 19F, 2D DOSY NMR spectroscopy.

In the last decade, the chemistry of meroterpenoids—conjugated molecules formed from isoprenyl fragments through biosynthetic pathways—has developed rapidly. The class includes some natural metabolites and fully synthetic fragments formed through nonbiological synthesis. In the field of synthetic receptors, a range of structures can be achieved by combining fragments of different classes of organic compounds into one hybrid macrocyclic platform which retains the properties of these fragments. This review discusses the successes in the synthesis and practical application of both natural and synthetic macrocycles. Among the natural macrocyclic meroterpenoids, special attention is paid to isoprenylated flavonoids and phenols, isoprenoid lipids, prenylated amino acids and alkaloids, and isoprenylpolyketides. Among the synthetic macrocyclic meroterpenoids obtained by combining the “classical” macrocyclic platforms, those based on cyclodextrins, together with meta- and paracyclophanes incorporating terpenoid fragments, and meroterpenoids obtained by macrocyclization of several terpene derivatives are considered. In addition, issues related to biomedical activity, processes of self-association and aggregation, and the formation of host–guest complexes of various classes of macrocyclic merotenoids are discussed in detail.

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