The cyclopentane carbocyclic ring system, while ubiquitous in Nature, is not usually considered a privileged core structure for the development of a drug candidate due, in part, to a perceived synthetic intractability of stereochemically complex target molecules. In this Review, we demonstrate that the cyclopentane motif has been utilized as an effective core scaffold for several highly successful medicinal chemistry programs and, thus, has provided an underappreciated yet significant value for biomedical research. Moreover, the modern synthetic methods highlighted in this work offer a wealth of attractive and accessible technologies for the stereocontrolled construction of exceedingly complex cyclopentanoid chemotypes of natural and unnatural origin. We contend that cyclopentanes should be regarded as privileged scaffolds for drug discovery research and that expanded screening campaigns of novel cyclopentane-based small molecule libraries for therapeutically relevant biological properties will have a favorable impact on the development of the active pharmaceutical ingredients (APIs) of tomorrow.
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