Macrocycles are great drug candidates and tool compounds for chemical-biology applications. The reduced flexibility of macrocycles improves selectivity in binding to a biological target. Study of all the factors that influence the topology of a macrocycle can be applied to the synthesis of new compounds with designed properties. Our group is investigating a class of [13]-macrodilactones and we find that C7, alpha to the ester carbonyl, is the key atom that guide the topology of this family of compounds. Here we report the synthesis of a [13]-macrodilactone substituted with a p-bromophenyl unit at C7 of the macrocyclic backbone. Different aromatic heterocycles were attached into [13]-macrodilactones via Suzuki cross coupling to increase the polarity of the hydrophobic macrocycles. Principal component analysis (PCA) was performed on these molecules and showed that these new compounds addressed a unique area of chemical space when compared to the drugs and natural products. The anti-proliferation activity assays as well as solubility tests have also been conducted. The synthesis of new compounds with designed activities will be developed based on all these informations.

Synthesis of C7-substituted-phenyl-[13]-macrodilactones, principal component analysis (PCA), and antiproliferation assays

2019 Fall National Meeting

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