D:A Friedo-oleanane Lactones from the Stems of Mallotus repandus ⊥ Somyote Sutthivaiyakit,* ,† Jiraporn Thongtan, † Somchai Pisutjaroenpong, ‡ Kanitha Jiaranantanont, § and Palangpon Kongsaeree § Department of Chemistry, Faculty of Science, Ramkhamhaeng University, Bangkok 10240, Thailand, Chulabhorn Research Institute, Bangkok 10210, Thailand, and X-ray Crystallographic Laboratory, Department of Chemistry, Faculty of Science, Mahidol University, Bangkok 10600, Thailand Received November 30, 2000 Three new D:A-friedo-oleanane lactones, viz., 3-oxo-D:A-friedo-oleanan-27,16R-lactone (1), 3R-benzoyloxy- D:A-friedo-oleanan-27,16R-lactone (2), and 3-hydroxy-D:A-friedo-oleanan-27,16R-lactone (3) were isolated from the stems of Mallotus repandus. Extensive use of NMR spectroscopic techniques led to full assignment of all 1 H and 13 C chemical shifts. The structure for 2 was confirmed by X-ray diffraction analysis. Mallotus repandus (Willd.) Mueller-Arg. (Euphorbiaceae) is a creeping shrub commonly known as “Ma Kaai Khruea” in Thailand. 1 The aerial part has been used as an anti- inflammatory, antigastric ulcer, antiulcerogenic, and anti- hepatotoxic drug. Dry roots have been used as an insecti- cide and as a treatment for rheumatic arthritis, hepatitis, liver cirrhosis, and snakebite. Previous studies of this plant yielded bergenin, 2 diterpenic lactones, 3 δ-lactone triter- penes, 4,5 mallorepine, a cyano-γ-pyridone, 6 and hydrolyz- able tannins. 7 We report here the isolation and structure elucidation of three new D:A-friedo-oleanane lactones. Structures were supported by an X-ray analysis of 2. This is the first report of the occurrence of D:A-friedo-oleanane lactones in Euphorbiaceae plants. Results and Discussion The hexane extract of dried stems of M. repandus was subjected to repeated column chromatography to give three D:A-friedo-oleanane lactones (1-3). Identification of pure compounds was based on spectroscopic data. Compound 1, mp 350 °C, gave a violet coloration upon treatment with anisaldehyde-sulfuric acid staining reagent on a TLC plate after heating. The EIMS gave a molecular ion at m/z 454 corresponding to the molecular formula C 30 H 46 O 3 . The IR spectrum indicated the presence of a six- membered or larger ring lactone (CdO stretching at ν max 1730 cm -1 ,C-O stretching at 1118 cm -1 ) and showed Cd O stretching of a saturated ketone at 1714 cm -1 . The 1 H NMR spectrum showed six methyl group singlets and one methyl group doublet. The 13 C NMR spectrum showed the presence of 30 carbons consisting of seven methyl, 10 methylene, five methine, and six quaternary carbons together with two carbonyl signals at δ C 177.0 and 212.0. The 3-oxo friedelane skeleton was implied by the presence of a shielded methyl group signal at δ C 6.8, which was found to have a one-bond correlation with the methyl proton doublet at δ H 0.85 by a HETCOR experiment. 8 Multiplets between δ H 2.29-2.36 and a quartet at δ H 2.20 (J ) 6.8 Hz) were assigned to the C-2 methylene and C-4 methine protons, respectively. The presence of a signal at δ H 3.98 (dd, J ) 2.1, 3.2 Hz) indicating an oxymethine proton on a carbon bonded to an -OCO-R group, together with the 13 C signal at δ C 177.0 corresponding to a carbonyl carbon, indicated a lactone moiety. Friedelane-type triterpenes are proposed to have rings D and E in a boat-boat conformation. 9 This being the case, it could clearly be envisaged using molecular models that the six-membered lactone ring can only be formed favorably as a 27,16-R-lactone ring. The dihedral angle between protons H-15 and H-16 is about 60°, thus giving rise to the small 3 J coupling constants observed. Compound 1 was therefore proposed to be 3-oxo-D:A-friedo-oleanan-27,16R- lactone. Extensive use of NMR techniques including 1 H- 1 H COSY, 13 C- 1 H COSY (HETCOR), and long-range 13 C- 1 H correlation (COLOC) (Figure 1, Supporting Information) led to complete assignments of all 1 H and 13 C shift values as indicated in the Experimental Section. Compound 2, mp 340-342 °C, gave a violet coloration upon treatment with anisaldehyde-sulfuric acid reagent and a dark blue color in response to phosphomolybdic acid. The EIMS showed a molecular ion at m/z 560 correspond- ing to the molecular formula C 37 H 52 O 4 . The IR spectrum showed absorption bands at ν max 1731 and 1712 cm -1 for CdO stretching of a large-ring lactone and an aryl ester, respectively. The 1 H NMR spectrum showed a pattern of signals similar to that found for compound 1, except for the absence of multiplets between δ H 2.20-2.36, which had been assigned as C-2 methylene and C-4 methine protons ⊥ In honor of Professor Wolfgang Kraus upon his retirement. * To whom correspondence should be addressed. Tel: +66 2 319 1900. Fax: +66 2 310 8401. E-mail: somyote@ram1.ru.ac.th. † Ramkhamhaeng University, Bangkok. ‡ Chulabhorn Research Institute, Bangkok. § Mahidol University, Bangkok. 569 J. Nat. Prod. 2001, 64, 569-571 10.1021/np0005560 CCC: $20.00 © 2001 American Chemical Society and American Society of Pharmacognosy Published on Web 04/17/2001