22,25-Epoxylanostane triterpenoids indicated protective effects against oxygen-glucose deprivation/reoxygenation (OGD/R)-induced myocardial injury in a previous study. In order to discover potent cardioprotective agents, 20 22,25-epoxylanostane triterpenoids, including inonotsuoxides A and B, ganodercochlearins A and B, were synthesized from inotodiol (1). The structures of inonotsuoxide B and ganodercochlearin A are revised as 22R,25-epoxylanosta-8-en-3β,24R-diol (6) and 22S,25-epoxylanosta-7,9(11)-dien-3β,24R-diol (12) respectively, based on synthesis, spectroscopic data analysis, and X-ray crystallography. Compounds 13-16 and 22 showed potential protective activity against OGD/R-induced injury in H9c2 cells at a concentration of 20 μM. After OGD/R treatment, the most active compounds 13 and 22 at 5 μM increased cell viability by 11.4% and 6.4% respectively, whereas the positive control diazoxide was 14.9% at 100 μM. Flow cytometric analysis and JC-1 staining assay revealed that 13 suppressed OGD/R-induced apoptosis and the mitochondrial membrane potential in H9c2 cells. Compound 13 may serve as a potential lead cardioprotective agent for further development.