Immunosuppressive spirocyclic labdane diterpenoids from Holocheila longipedunculata.

Phytochemical study on Holocheila longipedunculata has revealed twenty previously undescribed spirocyclic labdane diterpenoids, named hololabdanes (1-20). Their chemical structures were elucidated through comprehensive spectroscopic analysis, and the absolute configuration of hololabdane A (1) was determined via single-crystal X-ray diffraction. Notably, hololabdane I (17) and 16-epi-hololabdane I (18) feature a rare pyrrolo [2,1-b] oxazolidinone moiety, while hololabdane J (19) and 2'-epi-hololabdane J (20) possess a distinctive peroxide bridge. Biological evaluations revealed that these spirocyclic labdanes exhibit potential immunosuppressive activity. In particular, compounds 5, 7, and 11 exhibited potent inhibition effects against IFN-γ secretion from T cells, with IC50 values of 1.21, 4.50, and 2.88 μM, respectively. Additionally, compounds 5 and 11 inhibited T cell proliferation, with IC50 values of 1.30 and 9.27 μM, respectively.