Enantioselective Synthesis of Homoisoflavanones by Asymmetric Transfer Hydrogenation and Their Biological Evaluation for Antiangiogenic Activity

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

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Abstract

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.

Original languageEnglish (US)
Pages (from-to)9995-10011
Number of pages17
JournalJournal of Organic Chemistry
Volume84
Issue number16
DOIs
StatePublished - Aug 16 2019

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ASJC Scopus subject areas

  • Organic Chemistry

Cite this

Heo, M., Lee, B., Sishtla, K., Fei, X., Lee, S., Park, S., Yuan, Y., Lee, S., Kwon, S., Lee, J., Kim, S., Corson, T. W., & Seo, S. Y. (2019). Enantioselective Synthesis of Homoisoflavanones by Asymmetric Transfer Hydrogenation and Their Biological Evaluation for Antiangiogenic Activity. Journal of Organic Chemistry, 84(16), 9995-10011. https://doi.org/10.1021/acs.joc.9b01134