title: Divergent synthesis and evaluation of inhibitory activities against cyclooxygenases-1 and -2 of natural withasomnines and analogues.
abstract: The divergent synthesis of natural withasomnines and analogues was achieved from 4-hydroxypyrazoles, which was prepared via alkaline hydrolysis of the Baeyer-Villiger oxidation products from 4-formylpyrazoles. Key steps of this synthesis are regioselective Claisen rearrangement of 4-allyloxypyrazoles and the Suzuki-Miyaura coupling of 5,6-dihydro-4H-pyrrolo[1,2-b]pyrazol-3-yl trifluoromethanesulfonate and commercially available arylboronic acids. The Suzuki-Miyaura coupling at the final step of this strategy enabled facile access to natural withasomnines and their analogues. The biological activities of the twelve synthesized compounds against cyclooxygenases-1 and -2 (COX-1 and COX-2) were evaluated.
authors.affiliation: Laboratory of Pharmaceutical Organic Chemistry, Osaka University of Pharmaceutical Sciences, Osaka University of Pharmaceutical Sciences; 4–20–1 Nasahara, Takatsuki, Osaka 569–1094, Japan. usami@gly.oups.ac.jp
authors.forename: Yoshihide
authors.initials: Y
authors.lastname: Usami
authors.forename: Ryo
authors.initials: R
authors.lastname: Watanabe
authors.forename: Yuiko
authors.initials: Y
authors.lastname: Fujino
authors.forename: Makio
authors.initials: M
authors.lastname: Shibano
authors.forename: Chihiro
authors.initials: C
authors.lastname: Ishida
authors.forename: Hiroki
authors.initials: H
authors.lastname: Yoneyama
authors.forename: Shinya
authors.initials: S
authors.lastname: Harusawa
authors.forename: Hayato
authors.initials: H
authors.lastname: Ichikawa
mesh_terms: D001688:Biological Products / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D051545:Cyclooxygenase 1 / Q000378:metabolism*; D051546:Cyclooxygenase 2 / Q000378:metabolism*; D016861:Cyclooxygenase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D015394:Molecular Structure; D011720:Pyrazoles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D001688:Biological Products; D016861:Cyclooxygenase Inhibitors; D011720:Pyrazoles; C568582:withasomnine; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2