Three minor ent-kaur-16-ene-type diterpene from croton tonkinensis gagnep

Journal of Chemistry, Vol. 43 (2), P. 263 - 264, 2005<br /> <br /> <br /> THREE MINOR ENT-KAUR-16-ENE-TYPE DITERPENE FROM<br /> CROTON TONKINENSIS Gagnep.<br /> Received 29th-Dec.-2004<br /> Phan Minh Giang1, Hideaki Otsuka2, Phan Tong Son1<br /> 1<br /> Faculty of Chemistry, College of Natural Science, Vietnam National University, Hanoi<br /> 2<br /> Graduate School of Biomedical Sciences, Hiroshima University, Hiroshima, Japan<br /> <br /> <br /> Summary<br /> Three diterpenoids with ent-kaur-16-ene skeleton, namely, ent-11 -acetoxy-7 ,14 -<br /> dihydroxykaur-16-en-15-one, ent-18-hydroxykaur-16-ene and ent-kaur-16-en-15-oxo-18-oic acid<br /> were isolated from the MeOH extract of the dried leaves of Croton tonkinensis Gagnep.<br /> (Euphorbiaceae) by successive chromatographic separation on silica gel, ODS gel and HPLC on<br /> ODS. Their structures were established on the basis of spectroscopic analyses.<br /> Keywords: Croton tonkinensis, Euphorbiaceae, ent-kaur-16-ene, diterpenoid.<br /> <br /> The leaves of the endemic Vietnamese systems was demonstrated to be an efficient<br /> medicinal plant Croton tonkinensis Gagnep. method in the purification of the minute amount<br /> (Euphorbiaceae) has been used in the treatment of compounds, which were concentrated in the<br /> of gastric and duodenal ulcers [1]. In our first subfractions by successive column chroma-<br /> attempt to investigate the phytochemical tography on silica gel followed by column<br /> constituents of this plant, the main compound chromatography on reversed-phase ODS gel.<br /> was isolated as a new ent-kaur-16-en-15-one Compounds 1 - 3 were obtained as amor-<br /> [2]. Later, the acting mechanism of the herbal phous powders in the quantities of ca. 2 mg of<br /> remedy was discovered by us, at least in part, each. In view of the paucity of material the<br /> through the ability of this compound to inhibit structures of these compounds were elucidated<br /> the activation of the transcription factor nuclear<br /> mainly on the basis of the 1H NMR spectra,<br /> factor kappa B (NF- B) [3]. Guided by the which were recorded on a high field NMR<br /> activity toward the inhibition of NF- B, further instrument (JEOL JNM-ECP 500, 500 MHz).<br /> new ent-kauranoids were isolated and Considering the 1H NMR signals and the co-<br /> structurally determined [3, 4]. In addition, long- occurrence of the other ent-kaurane-type<br /> chain alkyl alcohols [5] and flavonoid diterpenoids previously known from this plant<br /> glucosides [6] were isolated and structurally [2 - 4], 1 - 3 were also assumed to belong to the<br /> identified. Our continuous search for the other<br /> ent-series of kaurane-type diterpenoids. The 1H<br /> ent-kauranoids from this plant led to the<br /> NMR spectra of ent-kaur-16-enes 1, 2 and 3<br /> isolation of three minor diterpenoids 1 - 3, the<br /> were super-imposable with those reported in the<br /> structure elucidation of which is described in<br /> this paper. The extraction and isolation literature [7 - 9] of ent-11 -acetoxy-7 ,14 -<br /> procedures were carried out as described dihydroxy-kaur-16-en-15-one, ent-kaur-16-en-<br /> previously [3, 4]. Preparative HPLC on ODS 15-oxo-18-oic acid, and ent-18-hydroxykaur-<br /> columns using MeOH in water as solvent 16-ene, respectively.<br /> 263<br />  AcO<br /> <br /> <br /> H<br /> H<br /> H OH<br /> O<br /> O H<br /> H<br /> OH HO<br /> H HOOC<br /> <br /> <br /> <br /> 1 2 3<br /> <br /> Ent-11 -acetoxy-7 ,14 -dihydroxykaur-16- diseases and cancer chemoprevention.<br /> en-15-one (1): Amorphous powder. 1H NMR<br /> (CDCl3, 500 MHz): 0.87 (3H, s, 19-CH3), 0.93 Acknowledgements: This research was<br /> (3H, s, 18-CH3), 1.06 (3H, s, 20-CH3), 3.06 (1H, supported by the International Foundation for<br /> br s, H-13), 4.39 (1H, br d, J = 12.0 Hz, H-7), Science, Stockholm, Sweden, through a Grant to<br /> 4.92 (1H, s, H-14), 5.38 (1H, s, H-17A), 6.11 Dr. Phan Minh Giang, and the Basic Research<br /> (1H, s, H-17B). Program in Natural Science of Vietnam.<br /> Ent-kaur-16-en-15-oxo-18-oic acid (2): References<br /> Amorphous powder. 1H NMR (CDCl3, 500<br /> MHz): 1.13 (3H, s, 20-CH3), 1.18 (3H, s, 19- 1. Vo Van Chi. Dictionary of Vietnamese<br /> CH3), 3.05 (1H, br s, H-13), 5.25 (1H, s, H- Medicinal Plants, Publ. House Med., Ho<br /> 17A), 5.94 (1H, s, H-17B). Chi Minh City, P. 622 - 623 (1997).<br /> Ent-18-hydroxykaur-16-ene (3): Amorphous 2. Phan Tong Son, Phan Minh Giang, C. T. Walter.<br /> powder. 1H NMR (CDCl3, 500 MHz): 0.76 (3H, s, Austr. J. Chem., 53, P. 1003 - 1005 (2000).<br /> 19-CH3), 1.03 (3H, s, 20-CH3), 2.39 (2H, d, J = 11.9 3. Phan Minh Giang, H. Z. Jin, Phan Tong<br /> Hz, 2H-15), 2.61 (1H, br s, H-13), 3.10 (1H, d, J = Son, J. H. Lee, Y. S. Hong, J. J. Lee. J. Nat.<br /> 10.8, H-18A), 3.41 (1H, d, J = 10.8, H-18B), 4.92 Prod., 66, P. 1217 - 1220 (2003).<br /> (1H, s, H-17A), 4.94 (1H, s, H-17B). 4. Phan Minh Giang, Phan Tong Son, J. J. Lee,<br /> The accumulation of ent-kaurane-type H. Otsuka. Chem. Pharm. Bull., 52, P. 879 -<br /> diterpenoids in C. tonkinensis has been well 882 (2004).<br /> documented. The presence of three minor 5. Phan Minh Giang, J J. Lee, Phan Tong Son.<br /> diterpenoids, albeit in small amount, is an Vietnam J. Chem., 42 (1), P. 132 (2004).<br /> additional proof for the significant role of ent- 6. Phan Minh Giang, Phan Tong Son. Vietnam<br /> kaurane-type diterpenoids as chemotaxonomic J. of Chem., 42 (1), P. 125 - 128 (2004).<br /> markers of this plant. Ent-kaurane diterpenoids,<br /> 7. F. Nagashima, M. Kondoh, T. Uematsu, A.<br /> possessing an enone moiety at C-15/C-16 in<br /> Nishiyama, S. Saito, M. Sato, Y. Asakawa.<br /> ring D, like compounds 1 and 2, were known as<br /> Chem. Pharm. Bull., 50, P. 808 - 813 (2002).<br /> good acceptors of nucleophiles, such as the<br /> sulhydryl group of the cysteine residue, in a 8. A. G. Gonzalez, B. M. Fraga, M. 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