Eight hetereocyclic compounds conflamides B-I with an unprecedented skeleton and their precursor conflamide A were isolated from the mushroom Albatrellus confluens. Their structures and absolute configurations were determined by use of NMR studies, total synthesis, and calculated ECD spectra. Conflamides D and E were found to exhibit potent inhibition against LPS-induced B lymphocyte cell proliferation with IC50 values 1.48 and 5.71 μM, respectively.