ALT Table of Contents graphic showing the structure of a molecule comprising a Nile Red fluorophore covalently linked to a spironaphthoxazine, above a stylised vesicle membrane with disordered and ordered phases. Text says RESOLFT super-resolution microscopy and membrane polarity sensing.

ALT Title: Synthesis of meta-substituted arene bioisosteres from [3.1.1]propellane Panel 1: Bioisosteres for para-substituted arenes are well established, whereas isosteres for meta-substituted arenes are lacking. Recent approaches are bicyclohexanes, bridge-substituted bicyclopentanes, ladderanes and substituted cubanes. Most of them lack the correct exit vector angle of 120°. Panel 2: Synthesis of [3.1.1]propellane via a Kulinkovich, TiCl4, Dibromocarbene addition. We postulated that bicyclo[3.1.1]heptanes can be derived by reaction of [3.1.1]propellane producing exit vector bonds with the ideal 120° angle. Panel 3: Explored reactivity of [3.1.1]propellane. Addition of sulfur-radicals, carbon-iodides, MacMillan's three component reaction resulting in N-substituted bicycloheptanes. Also shown is a derivatisation of the derived bicyclo[3.1.1]iodides via Kumada-cross coupling or a lithiation strategy. Panel 4: Synthesis and biochemical testing of the bioisosteric analogue of Sonidegib.