Synthesis of the active form of loxoprofen by using allylic substitutions in two steps.
High regioselectivity for allylic substitution of the cyclopentenyl picolinate 5 with benzylcopper reagent was attained with ZnBr(2), and the finding was applied to the p-BrC(6)H(4)CH(2) reagent. The cyclopentene moiety in the product was reduced to the cyclopentane, and the p-BrC(6)H(4) was converted to the "Cu"C(6)H(4) for the second allylic substitution with picolinate 8 to furnish the title compound after oxidative cleavage of the resulting olefin moiety.
Hyodo
Tomonori
T
Department of Biomolecular Engineering, Tokyo Institute of Technology, 4259 Nagatsuta-cho, Midori-ku, Yokohama 226-8501, Japan.
Kiyotsuka
Yohei
Y
Kobayashi
Yuichi
Y
D000498:Allyl Compounds / Q000737:chemistry*; D002384:Catalysis; D003517:Cyclopentanes / Q000138:chemical synthesis* / Q000737:chemistry; D015394:Molecular Structure; D010084:Oxidation-Reduction; D010666:Phenylpropionates / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D010848:Picolinic Acids / Q000737:chemistry
D000498:Allyl Compounds; D003517:Cyclopentanes; D010666:Phenylpropionates; D010848:Picolinic Acids; C040656:loxoprofen; C030614:picolinic acid