4-Aminocyclopentane-1,3-diols as platforms for diversity: synthesis of a screening library?

MedChemComm Pub Date: 2013-12-02 DOI: 10.1039/C3MD00252G

Abstract

Trisubstituted cyclopentanes have a discrete shapely curvature. While the central ring of these compounds is devoid of rotatable bonds, the pseudo rotation of the cyclopentane ring leads to a desirable disruption of planarity. This is favorable for aqueous solubility and enables addressing of wide-ranging conformational space. The sp3-rich framework of 4-aminocyclopentane-1,3-diols offers stereochemically defined attachment points for substituents and renders these fragment-like molecules good platforms for molecular diversity. By using an established N-selective polymer-assisted acylation protocol, these scaffolds with natural product-like properties were transformed into a screening library by attachment of substituents at defined positions. Here we describe the synthesis and characterization of these molecular platforms and their use as starting points for the construction of an 80-member library of 4-amidocyclopentane-1,3-diol monoethers. Five of the compounds displayed cytotoxicity in a tumor cell line assay with IC50 values in the low micromolar range.

Graphical abstract: 4-Aminocyclopentane-1,3-diols as platforms for diversity: synthesis of a screening library
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