title: Asymmetric synthesis and biological activities of natural product (+)-balasubramide and its derivatives.
abstract: The natural product (+)-balasubramide (3j) and its derivatives (3a-3i) were synthesized using a two-step asymmetric synthesis, and the biological activities of 3a-3j were determined in vitro. Methyl (2S,3R)-(+)-3-phenyloxirane-2-carboxylate (1h), the asymmetric synthesis of which was described in a previous paper, was selected as the starting material. Compounds 3a-3j were evaluated for their neuroprotective, antioxidative, and anti-neuroinflammatory effects. (+)-Balasubramide and its derivatives with different electronegative groups in the 6-phenyl ring produced little neuroprotection and antioxidation, but induced potent anti-neuroinflammatory effects in BV-2 microglial cells (with the exception of 3g). Compound 3c, with a trifluoromethyl group in its 6-phenyl ring, was a particularly potent anti-neuroinflammatory agent. These results demonstrated that the electronegativity of the 6-phenyl ring of (+)-balasubramide is an important determinant of its inhibitory effect on neuroinflammation. More electronegative substituents result in more potent anti-neuroinflammatory effects. Moreover, cytotoxicity assays indicated no significant effects of the tested compounds.
authors.affiliation: a College of Pharmacy , Guangdong Pharmaceutical University , Guangzhou P.R. China.
authors.forename: Jun
authors.initials: J
authors.lastname: Li
authors.affiliation: a College of Pharmacy , Guangdong Pharmaceutical University , Guangzhou P.R. China.
authors.forename: Jianzu
authors.initials: J
authors.lastname: Li
authors.affiliation: b State Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of Drug Screening , China Pharmaceutical University , Nanjing , P.R. China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Xu
authors.affiliation: b State Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of Drug Screening , China Pharmaceutical University , Nanjing , P.R. China.
authors.forename: Yunjie
authors.initials: Y
authors.lastname: Wang
authors.affiliation: b State Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of Drug Screening , China Pharmaceutical University , Nanjing , P.R. China.
authors.forename: Luyong
authors.initials: L
authors.lastname: Zhang
authors.affiliation: a College of Pharmacy , Guangdong Pharmaceutical University , Guangzhou P.R. China.
authors.forename: Li
authors.initials: L
authors.lastname: Ding
authors.affiliation: a College of Pharmacy , Guangdong Pharmaceutical University , Guangzhou P.R. China.
authors.forename: Yining
authors.initials: Y
authors.lastname: Xuan
authors.affiliation: b State Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of Drug Screening , China Pharmaceutical University , Nanjing , P.R. China.
authors.forename: Tao
authors.initials: T
authors.lastname: Pang
authors.affiliation: a College of Pharmacy , Guangdong Pharmaceutical University , Guangzhou P.R. China.
authors.forename: Hansen
authors.initials: H
authors.lastname: Lin
mesh_terms: D000577:Amides / Q000138:chemical synthesis / Q000737:chemistry*; D000818:Animals; D001688:Biological Products / Q000138:chemical synthesis / Q000737:chemistry*; D004852:Epoxy Compounds / Q000737:chemistry; D004951:Esterification; D006575:Heterocyclic Compounds, 3-Ring / Q000737:chemistry* / Q000302:isolation & purification; D051379:Mice; D017628:Microglia / Q000187:drug effects; D015394:Molecular Structure; D016716:PC12 Cells; D051381:Rats
chemical_list: D000577:Amides; D001688:Biological Products; D004852:Epoxy Compounds; D006575:Heterocyclic Compounds, 3-Ring; C000610669:balasubramide
keywords: Balasubramide; anti-neuroinflammatory effect; asymmetric catalysis; biological screening; synthesis