Open AccessEnantioselective Synthesis of Homoisoflavanones by Asymmetric Transfer Hydrogenation and Their Biological Evaluation for Antiangiogenic Activity
Author(s) -
Myunghoe Heo,
Bit Lee,
Kamakshi Sishtla,
Fenfen Xiang,
Sanha Lee,
Soojun Park,
Yue Yuan,
Seul Lee,
Sangil Kwon,
Jung-Eun Lee,
Sanghee Kim,
Timothy W. Corson,
SeungYong Seo
Publication year - 2019
Publication title -
journal of organic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.2
H-Index - 228
eISSN - 1520-6904
pISSN - 0022-3263
DOI - 10.1021/acs.joc.9b01134
Subject(s) - enantioselective synthesis , chemistry , stereocenter , macular degeneration , blindness , diabetic retinopathy , angiogenesis , kinetic resolution , choroidal neovascularization , retinal , endostatin , pharmacology , ophthalmology , cancer research , medicine , biochemistry , endocrinology , catalysis , optometry , diabetes mellitus
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.