New Diterpenes from Jatropha divaricata Richard W. Denton, † Wayne W. Harding, † Chadwick I. Anderson, † Helen Jacobs,* ,† Stewart McLean, ‡ and William F. Reynolds* ,‡ Department of Chemistry, University of the West Indies, Mona, Kingston 7, Jamaica, and Department of Chemistry, University of Toronto, 80 St. George Street, Toronto, Canada M5S 3H6 Received February 22, 2001 Extracts of the stems of Jatropha divaricata have yielded the two new diterpenes ent-3,14R- hydroxypimara-7,9(11),15-triene-12-one (3) and the rearranged pimarane ent-15(13f8)abeo-8(ethyl)- pimarane (4), which appears to be a new skeletal type. The rare cleistanthane diterpenes spruceanol (1) and cleistanthol (2) were also obtained. The large euphorbiaceous genus Jatropha L. is recog- nized as a source of several structural classes of diter- penes, 1 many of which are biologically active, possessing antitumor and cytoxic, 1a tumor-promoting, 1c or antimicro- bial activity. 1d Other types of compounds known to occur in Jatropha include alkaloids, 2 lignans, 3 and triterpenes. 4 Jatropha divaricata Sw. is a shrub that is endemic to Jamaica. 5 The latex has been screened for protease activ- ity, 6 but prior to this study the plant has not been subjected to thorough phytochemical investigation. In an initial fractionation of extracts of the aerial parts of J. divaricata, 7 the stems and bark were found to contain the diterpenes spruceanol (1) and cleistanthol (2), trans- triacontyl-4-hydroxy-3-methoxy cinnamate, and scopoletin. Compounds characterized from the leaves and twigs were ficaprenol-13, R-tocopherol, plastochromenol-9, and -sito- sterol. 7 Spruceanol (1) 8 and cleistanthol (2) 9 are the only two known naturally occurring members of the cleistan- thane series of diterpenes and have each been reported only once previously. Because of the marked bioactivity observed for 1 and 2 isolated from J. divaricata, a new supply of plant material was collected. Compounds 1 and 2 were reisolated, and the new diterpenes 3 and 4 were also obtained. Compound 3,C 20 H 28 O 3 , was determined to be ent-3,14R- hydroxypimara-7,9(11),15-triene-12-one from spectroscopic data. Signals in the 1 H NMR spectrum for the C-15,C-16 vinyl group, which is characteristic of pimarane diterpe- noids, 10 indicated that 3 was likely to be of this skeletal class. This group provided the starting point for formula- tion of that portion of the skeleton numbered C-7 through C-14 and the attached methyl groups. This was necessarily based on connectivity data obtained from HSQC and HMBC spectra, as this C-7 to C-14 residue contains no linear protonated sequences apart from the pendant vinyl group. The presence of the protonated sequences C-1 to C-3 and C-5 to C-6 was inferred from associations in the COSY spectrum. These groups were joined to the C-4 center bearing the gem-dimethyl group on the basis of HMBC cross-peaks, corroborated by biogenetic arguments, which also enabled linkage of the two major substructures, C-1 to C-6 and C-7 to C-14, to provide structure 3. The observed long-wavelength UV maximum, 289 nm, provided ad- ditional support for the presence of the ketone with extended conjugation. The 2-oxo derivative of 3 has been described as one of the diterpene stress metabolites of cassava roots, Manihot esculenta (Euphorbiaceae). 10 Compound 4,C 20 H 28 O 2 , displayed many similarities to 3 in the 1 H and 13 C NMR spectra. Ring A could be constituted as a CH 2 CH 2 CH(OH) group flanked by two quaternary carbons, the first bearing an angular methyl group and the other a gem-dimethyl group, and these centers are joined by the C-5 methine. A CH 2 CH 2 group was attached to this C-5 methine, from COSY data, to provide the substructure C-1 to C-7 and C-10 with the attached methyl groups. Another feature common to 3 and 4 was a vinyl group, and again this was used as the * To whom correspondence should be addressed. (H.J.) Tel: (876) 935- 8409. Fax: (876) 977-1835. E-mail: hjacobs@uwimona.edu.jm. (W.F.R.) Tel/ fax: (416) 978-3563. E-mail: wreynold@chem.utoronto.ca. † University of the West Indies. ‡ University of Toronto. 829 J. Nat. Prod. 2001, 64, 829-831 10.1021/np010098a CCC: $20.00 © 2001 American Chemical Society and American Society of Pharmacognosy Published on Web 06/01/2001