Stereoselective Synthesis of Chiral Isatin Containing Bisphosphonates as Potential Anti‐Resorption Bone Drugs

Abstract Bisphosphonates are currently the major class of drugs used for the treatment of osteoporosis, a disease that leads to bone fragility and increase in fracture risk that affects hundreds of million elderly individual worldwide. All commercially available bisphosphonates are achiral albeit their activity is demonstrated to be related to inactivation of specific enzymes. Cinchona alkaloid urea derivatives are efficient organocatalysts for the asymmetric aldol reaction of ketones to an isatin containing bisphosphonate precursor to provide a class of new chiral enantioenriched potentially anti‐resorption bone drugs. High chemical yields were generally achieved in a wide array of substrates tested and in several cases ee′s in the 60–96 % range could be observed.