New Clerodane Diterpenoids from Casearia membranacea by Ya-Ching Shen*, Cheng Lin Lee, Ashraf Taha Khalil,and Yuan-Bin Cheng Institute of Marine Resources, National Sun Yat-sen University, Kaohsiung, Taiwan, Republic of China and Ching-Te Chien Taiwan Forestry Research Institute, Taipei, Taiwan, Republic of China and Yao-Haur Kuo National Research Institute of Chinese Medicine, Taipei, Taiwan, Republic of China Bioassay-guidedfractionationofanAcOEtextractof Caseariamembranacea resultedintheisolationofsix new clerodane diterpenes, caseamembrins G±L (1 ± 6). The structures of the new compounds, including their relative configurations, were established by an extensive study of their spectral data, especially 2D NMR. The cytotoxicactivitiesoftheisolatedditerpenesagainsthumanoralepidermoid(KB),cervicalepitheloid(Hela), and liver (Hep59T/VGH) carcinoma cell lines were investigated. 1. Introduction. ±TheGenus Casearia isarichsourceofclerodane-typediterpenes [1±5], many of them with established cytotoxic [6±8] or immunomodulatory [9] activities. Casearia membranacea Hance (Flacourtiaceae) is a tree growing wildly in the northern region of Taiwan [10]. Recently, we reported the isolation of several diterpenesfromthesamespecies[11][12].Incontinuationofasearchfornewcytotoxic diterpenesfromlocalflora,wecarriedoutaphytochemicalinvestigationofanAcOEt extractof C.membranacea.Inthiscommunication,wewishtoreporttheisolationofsix new clerodane diterpenes, caseamembrins G±L (1 ± 6). The structures of the new compounds, including their relative configurations, were established by an extensive studyoftheirspectraldata,especially2DNMR.Thecytotoxicactivitiesoftheisolated diterpenes against human-cancer cell lines were assessed. 2. Results and Discussion. ±Themolecularformulaof 1 wasestablishedasC 28 H 40 O 8 from FAB-MS and 13 C-NMR spectra. The UV spectrum showed absorption attribut- able to a monosubstituted conjugated diene at l 223 nm. The IR spectrum displayed absorptionbandsdiagnosticofanOHgroup(3447cm 1 ),estercarbonyl(s)(1745and 1738cm 1 )andolefinicbond(s)(1645cm 1 ). 1 H-and 13 C-NMR Data ( Tables1 and 2) revealedthepresenceoftwoacetyloxyandbutanoyloxysubstituents.Thespectraldata of 1 wereingoodagreementwiththebasicskeletonofclerodanediterpenespreviously isolated from Casearia [7][8][13] and established the structure as rel- (2S,5R,6R,8S,9S,10R,18R,19S )-18,19-bis(acetyloxy)-18,19-epoxy-2-hydroxy cleroda- 3,13(16),14-trien-6-yl butanoate. The 1 H-NMR( Table1)of 1 revealedthepresenceoftwoacetategroupsat d 2.02and1.86.The 13 C-NMR ( Table2)showedtwoestercarbonylabsorptionsand d 170.2and170.0togetherwithtwoacetateMegroupsat d 21.7 and 21.3 and a butanoyl ester at d 173.1 (CO),36.6(CH 2 ),18.3(CH 2 ),and13.7(Me).Subtractingthe Helvetica Chimica Acta ±Vol.88(2005) 68  2005 Verlag Helvetica Chimica Acta AG, Zürich