title: Asymmetric synthesis and effect of absolute stereochemistry of YCZ-2013, a brassinosteroid biosynthesis inhibitor.
abstract: The four stereoisomers of 2RS,4RS-1-[[2-(2,4-dichlorophenyl)-4-(2-(2-propenyloxy)phenoxymethyl)-1,3-dioxolan-2-yl]methyl]-1H-1,2,4-triazole (YCZ-2013), a novel brassinosteroid biosynthesis inhibitor, were prepared. The diastereomers of 2RS,4R-5 and 2RS,4S-5 were prepared by using the corresponding optically pure R and S toluene-4-sulfonic acid 2,3-dihydroxypropyl ester (R-4,S-4). The enatiomerically and diastereomerically pure acetonide (5) was obtained by a method involving diastereoselective crystallisation of the tosylate salt, followed by re-equilibration with the mother liquor and chromatography. The optical purity of four target compounds (YCZ-2013) was confirmed by chiral high-performance liquid chromatography (HPLC) and NMR. The effects of these stereoisomers on Arabidopsis stem elongation indicated that the cis isomers of 2S,4R-YCZ-2013 and 2R,4S-YCZ-2013 exhibited potent inhibitory activity with IC50 values of approximately 24 ± 3 and 24 ± 2 nM, respectively. The IC50 values of the trans isomers of 2S,4S-YCZ-2013 and 2R,4R-YCZ-2013 are approximately 1510 ± 50 and 3900 ± 332 nM, respectively. Co-application of brassinolide (10nM), the most potent BR, and GA3 (1 μM) to Arabidopsis seedlings grown in the dark with 2R,4S-YCZ-2013 and 2S,4R-YCZ-2013 revealed that brassinolide recovered the induced dwarfism of Arabidopsis seedlings, whereas GA3 showed no effect.
authors.affiliation: Department of Biotechnology, Faculty of Bioresource Sciences, Akita Prefectural University, 241-438, Shimoshinjo, Nakano, Akita 010-0195, Japan. Electronic address: jmwang@akita-pu.ac.jp.
authors.forename: Keimei
authors.initials: K
authors.lastname: Oh
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Yamada
authors.forename: Yuko
authors.initials: Y
authors.lastname: Yoshizawa
mesh_terms: D017360:Arabidopsis / Q000254:growth & development / Q000378:metabolism; D001393:Azoles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D060406:Brassinosteroids / Q000096:biosynthesis*; D004149:Dioxoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D010937:Plant Growth Regulators / Q000378:metabolism; D018547:Plant Stems / Q000187:drug effects / Q000254:growth & development; D036226:Seedlings / Q000187:drug effects / Q000378:metabolism; D013237:Stereoisomerism; D014230:Triazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology
chemical_list: C000589843:1-((2-(2,4-dichlorophenyl)-4-(2-(2-propenyloxy)phenoxymethyl)-1,3-dioxolan-2-yl)methyl)-1H-1,2,4-triazole; D001393:Azoles; D060406:Brassinosteroids; D004149:Dioxoles; D010937:Plant Growth Regulators; D014230:Triazoles
keywords: Azole derivatives; Brassinosteroid biosynthesis inhibitor; Plant hormone