α-Cyclodextrin Encapsulation of Bicyclo[1.1.1]pentane Derivatives: A Storable Feedstock for Preparation of [1.1.1]Propellane
Masanobu Uchiyama describes the α-cyclodextrin encapsulation of bicyclo[1.1.1]pentane derivatives.
[1.1.1]Propellane is a highly strained molecule that represents the most convenient starting material for the synthesis of the bicyclo[1.1.1]pentane (BCP) unit, which is now widely recognized as a three-dimensional (3D) bioisostere of the benzene ring. Replacement of para-phenyl derivatives with 1,3-disubstituted BCP scaffolds can improve metabolic stability, solubility, and membrane permeability. However, the lack of straightforward and versatile synthetic methodologies to access multi-functionalized BCP derivatives is a significant impediment to realizing the full potential of this promising scaffold. To address this synthetic challenge and to contribute to the field of drug discovery, the group of Professor Masanobu Uchiyama from The University of Tokyo (Japan) started a project to develop innovative synthetic tools to access a variety of BCP derivatives.