Neovascular eye diseases are a major cause of blindness. Excessive angiogenesis is a feature of several conditions, including wet age-related macular degeneration, proliferative diabetic retinopathy, and retinopathy of prematurity. Development of novel anti-angiogenic small molecules for the treatment of neovascular eye disease pipeline for these diseases. We have previously reported the therapeutic potential of antiangiogenic homoisoflavanone derivatives with efficacy in retinal and choroidal neovascularization models, although these are due to racemic compounds due to the C3-stereogenic center in the molecules. This work presents asymmetric synthesis and structural determination of anti-angiogenic homoisoflavanones and pharmacological characterization of the stereoisomers. We describe an enantioselective synthesis of homoisoflavanones by virtue of ruthenium-catalyzed asymmetric transfer hydrogenation with dynamic kinetic resolution, providing a basis for further development of these compounds into novel experimental therapeutics for neovascular eye diseases.

Enantioselective synthesis of homoisoflavanones by asymmetric transfer hydrogenation and their biological evaluation for antiangiogenic activity

2019 Fall National Meeting

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