Two Triterpenoids with a Cyclobutane Moiety from Mastic: Structural Elucidation and Biological Evaluation

Two novel triterpenoids, cyclobutastics A (1) and B (2), were isolated from mastic (Pistacia lentiscus L.). Their structures were fully elucidated by NMR, ACD/SE, QCC-NMR, and ECD analysis. Compound 1 is characterized by a rare cyclization that forms a cyclobutane via the connection between C-1 and C-11, resulting in a fused 6/6/4/6/5 pentacyclic framework. Compound 2 features an unprecedented cyclobutane formed by the C-8-C-18 linkage, marking the first report of this structural motif in a natural triterpenoid. Compound 2 inhibited the proliferation of human colorectal adenocarcinoma SW480 and HCT116 cells, with IC₅₀ values of 15.2 ± 1.3 and 3.8 ± 0.7 μM, respectively, and exhibited moderate anti-inflammatory activity (IC₅₀ = 24.7 ± 1.5 μM).