Oxetanes as Versatile Elements in Drug Discovery and Synthesis

Sizable resources, both financial and human, are invested each year in the development of new pharmaceutical agents. However, despite improved techniques, the new compounds often encounter difficulties in satisfying and overcoming the numerous physicochemical and many pharmacological constraints and hurdles. Oxetanes have been shown to improve key properties when grafted onto molecular scaffolds. Of particular interest are oxetanes that are substituted only in the 3-position, since such units remain achiral and their introduction into a molecular scaffold does not create a new stereocenter. This Minireview gives an overview of the recent advances made in the preparation and use of 3-substituted oxetanes. It also includes a discussion of the site-dependent modifications of various physicochemical and biochemical properties that result from the incorporation of the oxetane unit in molecular architectures. Small but powerful: In recent years oxetanes have received newly gained attention in medicinal chemistry and by the synthetic community since it has been found that the introduction of an oxetane unit in the molecular scaffold of a compound can significantly modify its properties. This Minireview summarizes the advantages of oxetanes in drug discovery and outlines chemical transformations involving oxetanes. Copyright © 2010 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.