Selective 3- and 6-OH modification of (−)-clausenamide

(−)-Clausenamide is a drug candidate under Phase I clinical trial for treatment of Alzheimer's disease (AD). In order to elucidate the substituent related structure–activity relationship, six one-substituent modified (−)-clausenamide analogues were designed, and four of them, namely 3-O-methyl, 6-O-methyl, 3-des-hydroxyl and 6-des-hydroxyl analogues were prepared by selective 3- and 6-OH modification of (−)-clausenamide.