Reactions of activated lupane oxo-compounds with diazomethane: An approach to new derivatives of cytotoxic triterpenes

The reactions of diazomethane with activated carbonyl derivatives of lupane were investigated. Previously known cytotoxic oxo-compounds were chosen as substrates, which allowed new information on the structure-activity relationships of this group of compounds to be obtained. Reactions of lupane derivatives containing an unsaturated aldehyde, alpha-diketones or 18,19-seco-triketones with diazomethane gave 1,3-dipolar and carbene addition products, for example oxirane and dihydropyrazole derivatives, along with products arising from homologation of cyclic ketones, such as methyl enol ethers. We synthesised seventeen new compounds containing dihydropyrazole, oxirane, cyclopropane or 3-methoxycyclohex-2-en-1-one rings on the triterpenic skeleton. All compounds were tested for their in vitro cytotoxic activity against the T-lymphoblastic leukaemia CEM cell line.