Abstract: Alzheimer´s disease (AD) is a progressive neurodegenerative disorder associated with memory impairment and cognitive deficit. It is characterized by low levels of the neurotransmitter acetylcholine (ACh) in the brain of AD patients. The inhibition of acetylcholinesterase (AChE), the enzyme that catalyzes ACh hydrolysis, is the main therapeutic strategy used to treat AD. In the healthy brain, another enzyme, namely butyrylcholinesterase (BChE), is involved in the metabolic degradation of ACh. BChE activity increases as AD progresses, which suggests that BChE may play an important role at the latter stages of AD. Therefore, selective BChE inhibitors attract interest nowadays. The chemistry of lupane-type triterpenoids has been actively explored due to their biological and pharmacological properties. Abundant in many plants, these metabolites are valuable natural raw materials to perform chemical modifications. In the present work, we aimed to evaluate of natural and semisynthetic lupanes as potential in vitro cholinesterase inhibitors. Lupeol (1) (lup-20(29)-en-3β-ol) and calenduladiol (2) (lup-20(29)-en-3β,16β-diol) have been isolated from Chuquiraga erinacea subsp. erinacea (Asteraceae), an endemic species growing wildly in our region. Semisynthetic lupanes 3-16 have been prepared from them. All of them failed to inhibit AChE, but we found that most of them exhibited BChE inhibition. The best BChE inhibitors were 16-oxolup-20(29)-en-3β-ol and 3,16,30-trioxolup-20(29)-ene with IC₅₀ values of 28.9 and 21.5 µM respectively, an interesting result considering that the role of BChE is more relevant as the disease progresses.