Synthetic approaches to 2-(4-hydroxy-7-chromanyl)benzoic acids as antagonists of leukotriene B4.
Structural modification of 1 led to a series of 2-(4-hydroxy-7-chromanyl)benzoic acid LTB4 antagonists exemplified by 2 and 3. The use of an organostannane biaryl coupling, a non steroselective reduction and a chromatographic resolution limited the utility of this synthetic route. To address these issues, a new synthetic route was developed utilizing a palladium catalyzed coupling of aryl oxazolines in tandem with a stereospecific enone reduction as key synthetic steps. Resolution was achieved by fractional crystallization of a (S)-(-)-alpha-methylbenzylamine salt.
Chambers
R J
RJ
Central Research Division, Pfizer Inc, Groton, CT 06340, USA.
Koch
K
K
Biggers
M S
MS
Ramchandani
M
M
D001565:Benzoates / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D002851:Chromatography, High Pressure Liquid; D018102:Receptors, Leukotriene B4 / Q000037:antagonists & inhibitors*; D013237:Stereoisomerism
D001565:Benzoates; D018102:Receptors, Leukotriene B4