Enantioselective Synthesis of Homoisoflavanones by Asymmetric Transfer Hydrogenation and Their Biological Evaluation for Antiangiogenic Activity
journal contributionposted on 2019-08-05, 15:09 authored by Myunghoe Heo, Bit Lee, Kamakshi Sishtla, Xiang Fei, Sanha Lee, Soojun Park, Yue Yuan, Seul Lee, Sangil Kwon, Jungeun Lee, Sanghee Kim, Timothy W. Corson, Seung-Yong Seo
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 antiangiogenic small molecules for the treatment of neovascular eye disease is essential to provide new therapeutic leads for these diseases. We have previously reported the therapeutic potential of anti-angiogenic homoisoflavanone derivatives with efficacy in retinal and choroidal neovascularization models, although these are 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 accompanying dynamic kinetic resolution, providing a basis for the further development of these compounds into novel experimental therapeutics for neovascular eye diseases.
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Antiangiogenic Activity Neovascular eye diseasesC 3-stereogenic centerBiological Evaluationretinopathyenantioselective synthesisExcessive angiogenesismoleculeracemic compoundsnovel antiangiogenicAsymmetric Transfer Hydrogenationneovascular eye diseaseanti-angiogenic homoisoflavanone derivativeschoroidal neovascularization modelsneovascular eye diseasesage-related macular degenerationtransfer hydrogenationanti-angiogenic homoisoflavanonesEnantioselective Synthesis