5'-Hydroxyisoavrain-villeol, a new biominated diphenylmethane derivative isolated from the tropical green macrophyte, Avrainvillea nigricans, exhibits potent PTP1B inhibiting activity. We report here the first synthesis of 5'-hydroxyisoavrain-villeol and its derivatives (Scheme 1). 3,4-Dihydroxybenzoldyhyde was methylated and nitrated to give the nitro compound 2. Reduction the nitro group led to the amino compound 3, which was converted to the bromide 4 via the diazonium salt formation and Sandmeyer reaction. Ester reduction formed the benzyl alcohol 5 as the key intermediate for the synthesis of the target compound. Treatment of 5 with acetic anhydride gave ester 6, which reacted with the benzyl alcohol 5 in the presence of aluminum chloride to provide the methyl derivative of 5'-hydroxyisoavrain-villeol. Finally, demethylation of 6 led to the target compound as a light yellow oil mixtur. Optimization of the best reaction conditions and evaluation of their PTP1B inhibiting activity are being done in our research laboratory.

Total synthesis of 5'-hydroxyisoavrain-villeol and its derivatives

242nd National Meeting (2011)

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