Total synthesis of a natural antioxidant and structure-activity relationships of related compounds.
A total synthesis of benzodioxole derivative 1 was achieved via a palladium(0)-catalyzed cross-coupling reaction in a 68% overall yield (4 steps). A novel series of benzodioxoles bearing a variety of aromatic and heterocyclic rings was also prepared and the antioxidative activity evaluated using in vitro model systems. Structure-activity studies revealed that i) intramolecular hydrogen-bonding in the phenol moiety reduced activity, ii) introduction of disubstituents at the ortho location relative to the phenol increased activity, and iii) the methylenedioxy function contributed to stabilization of the phenoxy radical. Among of these compounds, 5,7-di-(4-methoxyphenyl)-4-methoxy-6-hydroxy-1,3-benzodioxole (7p) was the most favorable agent and more potent than n-propyl gallate.
Jinno
S
S
Central Research Laboratory, Nippon Suisan Kaisha, Ltd., Tokyo, Japan.
Otsuka
N
N
Okita
T
T
Inouye
K
K
D000818:Animals; D000975:Antioxidants / Q000138:chemical synthesis* / Q000494:pharmacology; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D002855:Chromatography, Thin Layer; D004149:Dioxoles / Q000138:chemical synthesis* / Q000494:pharmacology; D005609:Free Radicals; D006168:Guinea Pigs; D066298:In Vitro Techniques; D009682:Magnetic Resonance Spectroscopy; D008862:Microsomes, Liver / Q000187:drug effects / Q000378:metabolism; D013055:Spectrophotometry, Infrared; D013329:Structure-Activity Relationship
C401227:5,7-di-(4-methoxyphenyl)-4-methoxy-6-hydroxy-1,3-benzodioxole; D000975:Antioxidants; D004149:Dioxoles; D005609:Free Radicals