Practical synthesis of hydroxychromenes and evaluation of their biological activity.
A simple and efficient seven steps synthesis of brodifacoum and difethialone from phenylacetyl chloride is described. The key synthetic strategies involve Friedel-Crafts acylation, intramolecular ring cyclization and condensation reaction in the presence of Brønsted-Lowry acids. It was found that brodifacoum showed favorable inhibiting activities on LPS-stimulated nitrite production in BV-2 microglia cells. Brodifacoum exhibited superior anti-inflammatory effects than difethialone. We expect that an efficient linear synthesis of 4-hydroxycoumarin derivatives and key fragments that are useful agents for the modulation of inflammation as well as inhibition of coagulation will be of practical use.
Institute of Life Science Research, Rexgene Biotech, Ochang, Chungbuk 363-838, Korea.
Jae-Chul
JC
Jung
Seikwan
S
Oh
D015110:4-Hydroxycoumarins / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D000818:Animals; D000925:Anticoagulants / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D002460:Cell Line; D051379:Mice; D017628:Microglia / Q000187:drug effects / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism
D015110:4-Hydroxycoumarins; D000925:Anticoagulants; D009569:Nitric Oxide; C013418:bromfenacoum; C060340:difethialone