Electrosynthesis of Stable Betulin‐Derived Nitrile Oxides and their Application in Synthesis of Cytostatic Lupane‐Type Triterpenoid‐Isoxazole Conjugates

Novel lupane-type triterpenoid-isoxazole conjugates were designed by direct placing of isoxazole linker at C(17) triterpenoid. The suggested synthetic sequence demonstrates successful combination electro-organic synthesis and conventional approaches. TEMPO-mediated electrooxidation betulin to betulinal was developed optimized boron-doped diamond anodes with potassium acetate as inexpensive supporting electrolyte. Betulinal-derived oxime further selectively electro-oxidized a graphite anode nitrile oxide, which proved be stable isolable species. same reaction performed 3β-lupane-3,28-diol. Nitrile oxides characterized 15N NMR X-ray crystallography. allowed creation library 1,3-dipolar cycloaddition reactions various alkynes. Some the title exhibit cytostatic properties against breast cancer cell line MCF7, glioblastoma multiform U-87 MG lung carcinoma A549 growth inhibition (GI50) concentrations up 11 μm, while being harmless immortalized human fibroblasts hTERT (GI50 >100 μm).