Three New Diterpenoids Based on the Novel Sarcopetalane Skeleton from Croton sarcopetalus Carola S. de Heluani, † Ce ´sar A. N. Catala ´n, ‡ Luis R. Herna ´ ndez, § Eleuterio Burguen ˜ o-Tapia, § and Pedro Joseph-Nathan* ,§ Instituto de Quı ´mica Orga ´ nica, Facultad de Bioquı ´mica, Quı ´mica y Farmacia, Universidad Nacional de Tucuma ´ n, Ayacucho 491, S. M. de Tucuma ´ n 4000, Argentina, and Departamento de Quı ´mica, Centro de Investigacio ´ n y de Estudios Avanzados, Instituto Polite ´ cnico Nacional, Apartado 14-740, Me ´ xico, D. F. 07000, Me ´ xico Received June 14, 1999 The roots of Croton sarcopetalus afforded three new diterpenoids (2-4) with a novel carbon skeleton that seems to be derived biosynthetically from a pimarane precursor. The essential oil of the roots gave trans-methylisoeugenol as the main constituent, along with 22 further compounds. The large phanerogamous family Euphorbiaceae has 317 genera with about 7500 species. 1 From these genera, the genus Croton, containing some 700 species, is distributed widely in the warm regions, less frequently in the temper- ate regions, and rarely in the cold regions of the Earth. Most of the species of this genus produce a variety of diterpenes, some of them with antitumor activity 2 and others produce skin inflammation characterized by an intense erythema followed by edema and hyperplasia and eye conjunctivitis. 3 Ingestion of some of these toxic diter- penes produces mouth mucous-membrane irritation, abun- dant salivary secretion, intestinal pain, and, in some cases, diarrhea. 4 Croton sarcopetalus Muell., commonly known as “lechero ´n” is a shrub that grows in northwestern and central Argentina, and its pubescence, leaf size, color, and indumentum vary with seasonal and altitudinal changes, edaphic factors, and so forth. 5 In previous work of C. sarcopetalus 6 we have described the complete 13 C NMR assignments and conformational evaluation of junceic acid and of three yucalexins, including yucalexin B-6 7 and yucalexin P-4 (1). 7 Continuing our study on the roots of this species, we now report the isolation and structure elucidation of the three new diterpenoids 2-4 having a novel carbon skeleton that we name sarco- petalane. The structures of these new diterpenoids were determined using 1D and 2D NMR techniques. In addition, we analyzed the essential oil of the roots by GC-MS, which allowed the identification of trans-methylisoeugenol as the main constituent, together with 22 other compounds. Results and Discussion The positive-ion HRFABMS of sarcopetalolide (2) showed a quasimolecular ion peak [M + H] + at m/z 317.2123 (calcd for C 20 H 29 O 3 , 317.2117 [M + H] + ), corresponding to the molecular formula C 20 H 28 O 3 . According to a DEPT experi- ment, the 16 sp 3 carbon atoms are distributed as four CH 3 , six CH 2 , three CH, and three C, while the sp 2 region shows a keto carbonyl, an ester carbonyl, and a trisubstituted double bond. The 1 H and 13 C NMR signals for the A and B rings are similar to those observed for yucalexin B-6 and yucalexin P-4 (1), 6,7 also isolated from the plant material. However, the 1 H NMR signals of the ABX system corre- sponding to the CH 2 (11)-CH(9) fragment appeared down- field when compared with those of yucalexin B-6. 7 The presence of a broad singlet at 4.98 ppm, ascribed to H-16, which, in the COSY experiment, showed correlation with the broad singlet at 5.47 ppm, assigned to H-15, together with the presence of a lactone carbonyl group signal at 171.5 ppm, instead of the ketone (C-12) at 211.5 ppm for yucalexin B-6, 6 as well as the HETCOR correlation of the methine signal at 90.3 ppm with the H-16 signal, indicated that the lactone ring closes at C-16. Furthermore, irradia- tion of H-16 at 4.98 ppm gave an 8% NOE effect of the H-15 signal at 5.47 ppm. In addition, the COSY experiment showed correlations of the H-14 signal at 2.69 ppm with the H-15, H-16, and CH 3 (17) signals at 5.47, 4.98, and 1.79 ppm, respectively, while the other H-14 signal, at 2.03 ppm, has correlations only with H-15 and CH 3 (17). To confirm the structure of sarcopetalolide (2), HMBC and NOESY experiments were performed, whose data are given in Table 1 and Table 2, respectively. All the above data, as well as the MMX calculations discussed below, are in agreement with structure 2. * To whom correspondence should be addressed. Tel.: (52) 5747-7112. Fax: (52) 5747-7113. E-mail: pjoseph@nathan.chem.cinvestav.mx. † Universidad Nacional de Tucuma ´ n (UNT). ‡ UNT, Research Member of the National Research Council of Argentina (CONICET). § Centro de Investigacı ´on y de Estudios Avanzados. Table 1. 13 C NMR Spectral Data of Compounds 2 and 4 (75.4 MHz, in CDCl3, TMS as Internal Standard) 2 C HMBC a 4 1 38.4 H-2, H-5, H-9, H-20 37.7 2 34.2 H-1 34.1 3 215.9 H-1, H-2 216.7 4 47.2 H-5, H-6, H-18, H-19 47.4 5 53.8 H-1, H-6, H-7, H-9, H-18, H-19, H-20 54.8 6 19.8 H-5, H-7 22.7 7 37.7 H-5, H-9, H-14, H-16 33.4 8 41.4 H-6, H-7, H-9, H-11, H-14, H-15, H-16 60.4 9 49.0 H-1, H-5, H-7, H-11, H-14, H-20 49.3 10 37.5 H-1, H-2, H-5, H-6, H-9, H-11, H-20 37.6 11 27.7 H-9 29.8 12 171.5 H-9, H-11, H-16 179.7 13 147.2 H-14, H-15, H-16, H-17 139.4 14 52.4 H-7, H-9, H-15, H-16, H-17 135.8 b 15 123.9 H-14, H-16, H-17 140.5 b 16 90.3 H-7, H-9, H-14, H-15 139.6 b 17 16.7 H-14, H-15 16.0 18 26.7 H-5, H-19 26.4 19 22.0 H-5, H-18 21.3 20 15.3 H-1, H-5, H-9 14.8 a At 500 MHz. b May be interchanged. 222 J. Nat. Prod. 2000, 63, 222-225 10.1021/np990292l CCC: $19.00 © 2000 American Chemical Society and American Society of Pharmacognosy Published on Web 01/27/2000