Hydroxylated boswellic and glycyrrhetinic acid derivatives: synthesis and cytotoxicity

Abstract

Oxidation of 2,3-dehydro-11-keto--boswellic acid gave derivatives holding extra hydroxyl groups at positions C-1, C-2 or C-1 and C-9, respectively. The synthesis of 2,3-dehydro-1,9-dihydroxy-11-keto--boswellic acid represents the first partial-synthetic access to this class of compounds. The synthetic strategy can be expanded easily, and a corresponding analogue derived from glycyrrhetinic acid was accessed by the same synthetic scheme in good overall yield. Boswellic and glycyrrhetinic acid 1,9-endoperoxides are intermediates for the synthesis of the 1,9-dihydroxylated compounds. These 1,9-endo-peroxides were highly cytotoxic for several human tumor cell lines but only diminished cytotoxicity was observed in SRB assays for the 1,9-dihydroxylated compounds.