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.

Chiral one-dimensional hydrogen-bonded architectures constructed from single-enantiomer phosphoric triamides

“…Chiral compounds are of great importance, not only because of their numerous potential applications in different domains of chemistry-based sciences or their predominance in biological systems, but also due to their attractive structural features and topologies (Prins et al, 1999). Many research teams have devoted their efforts to the design and discovery of various chiral compounds with different functional groups, and the alteration of structural requirements to achieve desired properties, most typically in nonlinear optics (Gu et al, 2016), circularly polarized light-emitting devices (Zinna et al, 2015), enantioselective catalysts (Headley & Marsden, 2007;Hua et al, 1987) or medicine (De Luca et al, 2017).…”