Synthesis of 3,16,30-trioxolup-20(29)-ene, a selective butyrylcholinesterase inhibitor, from a natural triterpene

MARÍA JULIA CASTRO; ANA ESTÉVEZ BRAUN; ANGEL G. RAVELO; ANA PAULA MURRAY; MARÍA BELÉN FARAONI

Santiago de Compostela

Congreso; The 17th International Electronic Conference on Synthetic Organic Chemistry; 2013

Six new lupanes type triterpenoids derivatives have been synthesized using lup-20(29)-en-3β,16β-diol (1) and 30-oxolup-20(29)-en-3β,16β-diol (2) as starting material. Ketones 3 (lup-20(29)-en-3,16-dione) and 4 (3,16,30-trioxolup-20(29)-ene) were obtained by Jone´s oxidation of compounds 1 and 2, respectively. Further reaction of 3 and 4 with hydroxylamine hydrochloride provided compounds 5 (lup-20(29)-en-16-one-3-oxime), 6 (lup-20(29)-en-3,16-dioxime), 7 (lup-20(29)-en-16-one-3,30-dioxime) and 8 (lup-20(29)-en-3,16,30-trioxime). Derivatives 3-8 were obtained in moderate - good yields. Their structures were confirmed by analysis of their 1H and 13C NMR and ESI-MS spectra. The complete assignation of the signals was achieved with the aid of 2D NMR experiments (COSY, HSQC, HMBC, NOESY). All of the new derivatives were evaluated as potential in vitro butyrylcholinesterase (BChE) inhibitors by the Ellman´s colorimetric method. Their anti acetylcholinesterase (AChE) activity was evaluated in order to determine the BChE/AChE selectivity of compounds 3-8. All of them failed to inhibit AChE, but we found that the best BChE inhibition was observed for 3,16,30-trioxolup-20(29)-ene (4) with an IC50 value of 21.5 M, which elicited a selective inhibitor profile.