DSpace at VNU: Application of the taraxerane-oleanane rearrangement to the synthesis of seco-oleanane triterpenoids from taraxerone

This article was downloaded by: [Ondokuz Mayis Universitesine] On: 06 November 2014, At: 09:39 Publisher: Taylor & Francis Informa Ltd Registered in England and Wales Registered Number: 1072954 Registered office: Mortimer House, 37-41 Mortimer Street, London W1T 3JH, UK Natural Product Research: Formerly Natural Product Letters Publication details, including instructions for authors and subscription information: http://www.tandfonline.com/loi/gnpl20 Application of the taraxerane–oleanane rearrangement to the synthesis of secooleanane triterpenoids from taraxerone a ab a Phan Minh Giang , Vu Minh Trang , Phan Tong Son & Katsuyoshi c Matsunami a Faculty of Chemistry, VNU University of Science, Vietnam National University, Hanoi, 19 Le Thanh Tong Street, Hanoi, Viet Nam b VNU University of Education, Vietnam National University, Hanoi, 144 Xuan Thuy Road, Hanoi, Viet Nam c Graduate School of Biomedical & Health Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima 734-8553, Japan Published online: 15 Sep 2014 To cite this article: Phan Minh Giang, Vu Minh Trang, Phan Tong Son & Katsuyoshi Matsunami (2015) Application of the taraxerane–oleanane rearrangement to the synthesis of seco-oleanane triterpenoids from taraxerone, Natural Product Research: Formerly Natural Product Letters, 29:1, 64-69, DOI: 10.1080/14786419.2014.958737 To link to this article: http://dx.doi.org/10.1080/14786419.2014.958737 PLEASE SCROLL DOWN FOR ARTICLE Taylor & Francis makes every effort to ensure the accuracy of all the information (the “Content”) contained in the publications on our platform However, Taylor & Francis, our agents, and our licensors make no representations or warranties whatsoever as to the accuracy, completeness, or suitability for any purpose of the Content Any opinions and views expressed in this publication are the opinions and views of the authors, and are not the views of or endorsed by Taylor & Francis The accuracy of the Content should not be relied upon and should be independently verified with primary sources of information Taylor and Francis shall not be liable for any losses, actions, claims, proceedings, demands, costs, expenses, damages, and other liabilities whatsoever or howsoever caused arising directly or indirectly in connection with, in relation to or arising out of the use of the Content Downloaded by [Ondokuz Mayis Universitesine] at 09:39 06 November 2014 This article may be used for research, teaching, and private study purposes Any substantial or systematic reproduction, redistribution, reselling, loan, sub-licensing, systematic supply, or distribution in any form to anyone is expressly forbidden Terms & Conditions of access and use can be found at http://www.tandfonline.com/page/termsand-conditions Natural Product Research, 2015 Vol 29, No 1, 64–69, http://dx.doi.org/10.1080/14786419.2014.958737 Application of the taraxerane –oleanane rearrangement to the synthesis of seco-oleanane triterpenoids from taraxerone Phan Minh Gianga*, Vu Minh Trangab, Phan Tong Sona and Katsuyoshi Matsunamic Downloaded by [Ondokuz Mayis Universitesine] at 09:39 06 November 2014 a Faculty of Chemistry, VNU University of Science, Vietnam National University, Hanoi, 19 Le Thanh Tong Street, Hanoi, Viet Nam; bVNU University of Education, Vietnam National University, Hanoi, 144 Xuan Thuy Road, Hanoi, Viet Nam; cGraduate School of Biomedical & Health Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima 734-8553, Japan (Received 19 June 2014; final version received 21 August 2014) Synthetic oleananes and seco-oleananes form a group of promising anti-inflammatory and cancer chemopreventive agents with an excellent safety profile These compounds are usually prepared by semi-synthesis from natural oleanane triterpenoids Since a taraxer-14-ene was reported to be rearranged into an olean-12-ene under mild reaction conditions, a rapid synthesis of seco-oleananes from taraxerone, which is a readily available starting material, was explored by us Treatment of taraxerone with m-chloroperoxybenzoic acid gave 14,15-epoxy lactones, which underwent the taraxerane –oleanane rearrangement leading to new seco-oleanane triterpenoids Keywords: taraxerone; Baeyer – Villiger rearrangement; 3,4-seco-oleanane oxidation; taraxerane – oleanane Introduction Numerous natural pentacyclic compounds arise from squalene through a variety of cyclisation modes under the catalytic action of oxidosqualene cyclases The pentacyclic triterpenoids are divided into many subgroups based on their carbon skeleton, of which lupane, oleanane and ursane are distinguished classes because of their widespread occurrence and biological, pharmacological or medicinal activities (Honda et al 2000; Laszczyk 2009) A number of publications have highlighted structure – activity relationships of oleananes, showing the importance of chemical modifications in improving potency of the natural oleananes (Sun et al 2006; Kazakova et al 2014) Several 100 synthetic oleananes and seco-oleananes have been synthesised and they are proved to be non-cytotoxic agents in the treatment of inflammatory diseases and cancer chemoprevention (Finlay et al 1997; Maitraie et al 2009; Liby & Sporn 2012) In most reports, these compounds were semi-synthesised from natural oleananes The rearrangement of 2a,14a-diepoxytaraxerane into olean-12-ene-2a,3b,15a-triol under mild reaction conditions reported by Banerji et al (1999) inspired a new synthetic approach As taraxerone (1) is a readily available taraxerane triterpenoid and possesses a C-14/C-15 double bond, new seco-A-ring oleananes can be prepared from by the Baeyer – Villiger oxidation, followed by the facile taraxerane – oleanane rearrangement described above Oxidation of the carbonyl group and epoxidation of the C-14/C-15 double bond give an epoxy lactone, which can subsequently undergo the taraxerane – oleanane rearrangement and lactone-ring opening, leading to seco-oleanane products (Scheme 1) We report herein the first synthesis of 3,4-secooleanane triterpenoids from taraxerone *Corresponding author Email: phanminhgiang@yahoo.com q 2014 Taylor & Francis Natural Product Research 29 11 O 10 23 24 27 19 30 20 18 21 22 13 17 26 25 12 14 15 65 28 16 a 63.8% O O b H CO C 62.5% OH O Downloaded by [Ondokuz Mayis Universitesine] at 09:39 06 November 2014 c 41.9% H3CO2C O HO d,e 99.3% HO2C HO OH Reagents: (a) MCBPA, CH2Cl2; (b) H2SO4, MeOH; (c) MCPBA, CH2Cl2, MeOH; (d) KOH, MeOH; (e) HCl, H2O Scheme Synthesis of and from Results and discussion Treatment of taraxerone (1) with m-chloroperoxybenzoic acid (MCPBA) in CH2Cl2 solution at room temperature led to the epoxidation of C-14/C-15 double bond and Baeyer – Villiger oxidation of C-3 ketonic group The HR-ESI-MS of the epoxy lactone product showed a peak at m/z 479.3493 ([M ỵ Na]ỵ), determining its molecular formula as C30H48O3 The 1H and 13C NMR determined the introduction of the C-14/C-15 epoxide ring [dH 3.04 (1H, br d, J ¼ 6.5 Hz); dC 57.2 and 68.6] on comparison with the NMR data of 14,15-epoxyepitaraxerol (Scheme S1) The A-ring lactone was determined by the chemical shifts of two C-4 methyl groups [dH 1.43 (3H, s) and 1.46 (3H, s)], C-4 (dC 86.2) and the lactone carbonyl group (dC 174.9) (Maitraie et al 2009; Tu et al 2009) The lactone ring of was cleaved by treatment with a catalytic amount of H2SO4 in MeOH to yield product An acid-catalysed transesterification of with MeOH might occur first, followed by dehydration of C-4 tertiary hydroxyl group at room temperature Independently, the skeletal taraxerane –oleanane rearrangement took place to give as the final product Mechanistically, the 14,15-epoxide ring was protonated, followed by epoxide ring opening to generate a carbocation at C-14 and C-15 hydroxymethine Then 1,2-migration of C-13 methyl group to C-14, followed by the cleavage of a H-12 proton afforded (Scheme 2) The structure of was characterised by NMR spectroscopic data, which revealed the presence of a methyl ester [dH 3.65 (3H, s); dC 51.6 and 174.5] and C-4/C-23 double bond [dH 4.68 (1H, s) and 4.88 (1H, s); dC 113.6 and 147.3] Characteristic signals of the C-12/C-13 double bond of the olean-12-ene [dH 5.31 (1H, t, J ¼ 3.0 Hz); dC 123.2 and 145.9] (Seo et al 1975) and a secondary hydroxymethine [dH 4.22 (1H, dd, J ¼ 11.5 Hz, 5.0 Hz); dC 68.4] were observed in the NMR spectra of On the other hand, the formation of 14,15-epoxy-3,4-seco-taraxerane (4) could be achieved by treatment of with MCPBA in a mixture of CH2Cl2 and CH3OH Carbon-13 signals of B, C, D and E rings were similarly observed for and 4; however, A-ring was cleaved by transesterification reaction, resulting in the appearance of two methyl groups at C-4 [dH 1.23 (3H, s) and 1.28 (3H, s)] and a methyl ester group [dH 3.66 (3H, s); dC 51.7 and 175.6] in the 1H and 13C NMR spectra of Compound was then converted into its corresponding hydroxy acid To prevent the possible dehydration of C-4 tertiary alcohol, was hydrolysed in 5% 66 P.M Giang et al CΗ3OH2 −CH3OH H3CO2C O O H3CO2C O O O H OCH3 H H CH3OH H H CH3OH H3CO2C H3CO2C Downloaded by [Ondokuz Mayis Universitesine] at 09:39 06 November 2014 OH −CH3OH2 H3CO2C OH OH Scheme Plausible synthetic pathway of from methanolic KOH (Tu et al 2009) Then quick acidification of the hydrolysis product with 10% aqueous HCl caused the taraxerane – oleanane rearrangement to afford 15-hydroxyolean-12-ene (5) The NMR spectra of showed signals of C-3 carboxylic acid (dC 176.3), hydroxy-bearing C-4 (dC 75.7), two C-4 methyl groups [dH 1.25 (3H, s) and 1.29 (3H, s); dC 27.5 and 33.4] (Tu et al 2009), C-12/C-13 double bond of the newly formed olean-12-ene [dH 5.31 (1H, t, J ¼ 3.0 Hz); dC 123.6 and 145.8] and C-15 hydroxymethine [dH 4.18 (1H, dd, J ¼ 11.5 Hz, 5.5 Hz); dC 68.3] Since the 14,15-epoxide rings of and are a-oriented due to facile approach of the reagent from the more exposed a-phase (Banerji et al 1999), the ring opening led to the a-oriented C-15 secondary hydroxyl group In the NOESY spectrum of (Scheme S2), a NOESY correlation was observed between H-15 (dH 3.04) and H3-26 (dH 1.15) As an evidence for the stereochemistry, H-15b of and gave a typical diaxial coupling constant (J ¼ 11.5 Hz) with axial H-16a Subsequently, methyl migration from C-13 to C-14 occurred from the same a-phase, leading to the a-orientation of C-14 methyl group Experimental 3.1 General experimental procedures All reagents were products for synthesis Taraxerone (1) was obtained by chromatographic isolation from Euphorbia hirta and Mallotus barbatus plants Optical rotations were measured on a Jasco P-1030 digital polarimeter (Jasco, Tokyo, Japan) FT-IR spectra were recorded on a Horiba FT-710 spectrophotometer (Horiba, Kyoto, Japan) HR-EI-MS were measured on a Jeol JMS-T100GCV mass spectrometer (Jeol, Tokyo, Japan) HR-ESI-MS and HR-APCI-MS were measured on an Applied Biosystems QSTAR XL mass spectrometer (Applied Biosystems, Foster City, CA, USA) 1H (500 MHz) and 13C NMR (125 MHz) spectra were recorded on a Bruker Avance 500 NMR spectrometer (Bruker, Billerica, MA, USA) Silica gel (0.040 – 0.063 mm) (Merck, Darmstadt, Germany) was used for column chromatography (CC) Thinlayer chromatography (TLC) was carried out on Merck TLC silica gel 60 F254 aluminium plates (Merck, Darmstadt, Germany) 3.2 Baeyer –Villiger oxidation of taraxerone (1) A mixture of (97.2 mg, 0.229 mmol) and MCPBA (119 mg, 0.69 mmol) in CH2Cl2 (8 mL) was stirred at room temperature for 72 h The mixture was washed with aqueous NaHCO3 and Downloaded by [Ondokuz Mayis Universitesine] at 09:39 06 November 2014 Natural Product Research 67 extracted with CH2Cl2 (20 mL £ 5) The CH2Cl2 extract was concentrated under reduced pressure to give a crude product The crude product was purified by CC on silica gel using nhexane – EtOAc 30:1, 19:1 and 9:1 to give (66.6 mg, 0.146 mmol, 63.8%) 14,15-Epoxy-3,4-seco-taraxerane-3,4-lactone (2): white amorphous powder; ½aŠ25 D þ 58.9 (c ¼ 0.14, CHCl3); IR (nmax, cm21): 1718, 1456, 1386, 1290, 1108; 1H NMR (CDCl3): d 0.79 (3H, s, 30-CH3), 0.86 (3H, s, 29-CH3), 1.05 (3H, s, 28-CH3), 1.08 (3H, s, 25-CH3), 1.12 (3H, s, 26-CH3), 1.18 (3H, s) (27-CH3), 1.43 (3H, s, 24-CH3), 1.46 (3H, s, 23-CH3), 3.04 (1H, br d, J ¼ 6.5 Hz, H-15); 13C NMR (CDCl3): d 16.9 (C-25), 17.8 (C-11), 22.5 (C-6), 23.4 (C-27), 23.6 (C-26), 24.5 (C-30), 25.8 (C-23), 30.1 (C-16), 30.9 (C-20), 31.2 (C-28), 31.9 (C-2), 32.4 (C-24), 32.9 (C-17), 33.1 (C-7), 33.5 (C-29), 33.9 (C-12), 34.5 (C-21), 36.4 (C-13), 37.4 (C-1), 37.6 (C22), 39.2 (C-19), 39.6 (C-8), 40.9 (C-10), 46.2 (C-9), 49.5 (C-18), 54.9 (C-5), 57.2 (C-15), 68.6 (C-14), 86.2 (C-4), 174.9 (C-3); Positive-ion HR-ESI-MS: m/z 479.3493 (Calcd for C30H48O3Na 479.3496) 3.3 Synthesis of methyl 15-hydroxy-3,4-seco-olean-4(23),12-dien-3-oate (3) Compound (36.4 mg, 0.08 mmol) was dissolved in MeOH (5 mL) Concentrated H2SO4 (1 drop) was added and the reaction mixture was stirred at room temperature for 24 h The mixture was concentrated under reduced pressure, washed with aqueous NaHCO3 solution and extracted with CH2Cl2 (20 mL £ 5) The CH2Cl2 extract was concentrated under reduced pressure to give a crude product The crude product was purified by CC on silica gel using n-hexane –EtOAc 50:1, 30:1 and 9:1 to give (23.3 mg, 0.05 mmol, 62.5%) Methyl 15-hydroxy-3,4-seco-olean-4(23),12-dien-3-oate (3): white amorphous powder; 21 ẵa24 D ỵ 102.7 (c ẳ 0.47, CHCl3); IR (nmax, cm ): 3444, 1734, 1636, 1465, 1384, 1299, 1176; H NMR (CDCl3): d 0.87 (3H, s, 28-CH3), 0.88 (6H, s, 29-CH3, 30-CH3), 0.95 (3H, s, 25-CH3), 1.09 (3H, s, 26-CH3), 1.18 (3H, s, 27-CH3), 1.75 (3H, s, 24-CH3), 2.20 (1H, m, H-2a), 2.37 (1H, ddd, J ¼ 16.0 Hz, 10.0 Hz, 6.0 Hz, H-2b), 3.65 (3H, s, -OCH3), 4.22 (1H, dd, J ¼ 11.5 Hz, 5.0 Hz, H-15), 4.68 (1H, s, H-23a), 4.88 (1H, s, H-23b), 5.31 (1H, t, J ¼ 3.0 Hz, H-12); 13C NMR (CDCl3): d 17.4 (C-26), 19.5 (C-25), 19.8 (C-27), 23.5 (C-24), 23.6 (C-30), 23.8 (C-11), 24.7 (C6), 28.5 (C-1), 28.9 (C-28), 30.9 (C-20), 33.1 (C-8), 33.3 (C-29), 34.0 (C-7), 34.6 (C-2), 34.7 (C21), 36.7 (C-16), 37.7 (C-9), 37.8 (C-22), 39.3 (C-10), 40.9 (C-14), 46.3 (C-19), 47.8 (C-18), 48.1 (C-17), 50.1 (C-5), 51.6 (-OCH3), 68.4 (C-15), 113.6 (C-23), 123.2 (C-12), 145.9 (C-13), 147.3 (C-4), 174.5 (C-3); HR-EI-MS: m/z 470.37525 (Calcd for C31H50O3 470.37599); Positiveion HR-ESI-MS: m/z 493.3650 (Calcd for C31H50O3Na 493.3652); Positive-ion HR-APCI-MS: m/z 471.3824 (Calcd for C31H51O3 471.3833) 3.4 Synthesis of methyl 14,15-epoxy-4-hydroxy-3,4-seco-taraxeran-3-oate (4) A mixture of (1 g, 2.358 mmol) and MCPBA (1.22 g, 7.07 mmol) in a mixture of CH2Cl2 and CH3OH (8 mL) was stirred at 8C for 40 min., then at room temperature for 72 h The mixture was washed with aqueous NaHCO3 and extracted with CH2Cl2 (20 mL £ 5) The CH2Cl2 extract was concentrated under reduced pressure to give a crude product The crude product was purified twice by CC on silica gel using n-hexane –EtOAc 30:1, 19:1 and 9:1 and n-hexane –EtOAc 15:1 and 9:1 to give (482.1 mg, 0.988 mmol, 41.9%) Methyl 14,15-epoxy-4-hydroxy-3,4-seco-taraxeran-3-oate (4): white amorphous powder; 21 ½aŠ25 D þ 28.8 (c ¼ 0.16, CHCl3); IR (nmax, cm ): 3497, 1723, 1445, 1386, 1204, 1177; H NMR (CDCl3): d 0.79 (3H, s, 30-CH3), 0.86 (3H, s, 29-CH3), 1.01 (1H, m, H-19a), 1.04 (1H, m, H-7a), 1.05 (2H, m, H-9, H-22a), 1.05 (3H, s, 28-CH3), 1.06 (3H, s, 27-CH3), 1.08 (3H, s, 25-CH3), 1.09 (2H, m, H-6a, H-12a), 1.15 (3H, s, 26-CH3), 1.18 (1H, m, 16a), 1.21 (1H, m, H-19b), 1.23 (1H, m, H-7b), 1.23 (3H, s, 24-CH3), 1.25 (1H, m, H-12b), 1.28 (3H, s, 23-CH3), 1.37 (1H, m, H-5), 68 P.M Giang et al Downloaded by [Ondokuz Mayis Universitesine] at 09:39 06 November 2014 1.43 (1H, m, H-21a), 1.45 (1H, m, H-22b), 1.47 (1H, m, H-6b), 1.49 (1H, m, H-11a), 1.62 (1H, m, H-2a), 1.64 (1H, m, H-11b), 1.97 (1H, m, H-18), 2.01 (1H, d, J ¼ 10.5 Hz, H-16b), 2.14 (1H, m, H-1a), 2.17 (1H, m, H-21b), 2.38 (1H, ddd, J ¼ 15.5 Hz, 10.5 Hz, 4.5 Hz, H-2b), 2.53 (1H, ddd, J ¼ 15.5 Hz, 10.5 Hz, 4.5 Hz, H-1b), 3.04 (1H, br d, J ¼ 6.5 Hz, H-15), 3.66 (3H, s, -OCH3); 13C NMR (CDCl3): d 17.2 (C-11), 20.7 (C-25), 22.1 (C-6), 23.4 (C-27), 23.7 (C-26), 24.4 (C-30), 27.4 (C-24), 28.9 (C-1), 30.1 (C-16), 30.9 (C-20), 31.3 (C-28), 32.9 (C-17), 33.2 (C-12), 33.6 (C-29), 33.9 (C-23), 34.11 (C-7), 34.14 (C-2), 34.6 (C-21), 36.5 (C-13), 37.6 (C-22), 39.2 (C-19), 39.6 (C-8), 41.8 (C-18), 42.3 (C-10), 46.1 (C-9), 51.5 (C-5), 51.7 (-OCH3), 57.2 (C-15), 68.8 (C-14), 75.8 (C-4), 175.6 (C-3); Positive-ion HR-ESI-MS: m/z 511.3752 (Calcd for C31H52O4Na 511.3758) 3.5 Synthesis of 4,15-dihydroxy-3,4-seco-olean-12-en-3-oic acid (5) Compound (50 mg, 0.102 mmol) in 5% methanolic KOH (9.5 mL) was stirred at room temperature for 72 h The reaction mixture was concentrated under reduced pressure, added with distilled water (18 mL), 10% aqueous HCl to pH and extracted with CH2Cl2 (20 mL £ 5) The CH2Cl2 extract was concentrated under reduced pressure to give (48.2 mg, 0.102 mmol, 99.3%) 4,15-Dihydroxy-3,4-seco-olean-12-en-3-oic acid (5): white amorphous powder; 21 ẵa25 D ỵ 30.7 (c ¼ 0.12, CHCl3); IR (nmax, cm ): 3482, 3219, 1698, 1457, 1383, 1276, 1224, 1201, 1180; H NMR (CDCl3 ỵ CD3OD): d 0.87 (3H, s, 28-CH3), 0.88 (6H, s, 29-CH3, 30CH3), 1.07 (3H, s, 25-CH3), 1.12 (3H, s, 26-CH3), 1.16 (3H, s, 27-CH3), 1.25 (3H, s, 24-CH3), 1.29 (3H, s, 23-CH3), 2.31 (1H, m, H-2a), 2.48 (1H, m, H-2b), 4.18 (1H, dd, J ¼ 11.5 Hz, 5.5 Hz, H-15), 5.31 (1H, t, J ¼ 3.0 Hz, H-12); 13C NMR (CDCl3 ỵ CD3OD): d 17.5 (C-26), 19.7 (C-27), 19.9 (C-25), 22.8 (C-6), 23.4 (C-11), 23.7 (C-30), 27.5 (C-24), 28.9 (C-28), 29.1 (C-1), 31.1 (C20), 33.1 (C-8), 33.3 (C-29), 33.4 (C-23), 34.4 (C-2), 34.7 (C-21), 35.3 (C-7), 36.8 (C-16), 37.6 (C-22), 39.0 (C-9), 41.0 (C-14), 41.3 (C-10), 46.4 (C-19), 47.8 (C-18), 48.2 (C-17), 51.4 (C-5), 68.3 (C-15), 75.7 (C-4), 123.6 (C-12), 145.8 (C-13), 176.3 (C-3); Positive-ion HR-ESI-MS: m/z 497.3597 (Calcd for C30H50O4Na 497.3601) Conclusion In addition to the traditional synthetic methodology of oleananes, a new approach to oleananes from taraxeranes can be explored By applying the facile taraxerane – oleanane rearrangement, taraxerone was successfully converted into new seco-oleanane triterpenoids The application of this method to expand the existing library of synthetic oleananes is the subject of ongoing investigations Supplementary material Synthesis of 14,15-epoxytaraxerol, Schemes S1 and S2 and spectra of compounds –5 relating to this article are available online Funding This research was funded by Vietnam National Foundation for Science and Technology Development (NAFOSTED) [grant number 104.01-2012.10] References Banerji J, Chatterjee A, Saha M, Dhara KP, Kanrar S, Mukherjee P, Neuman A, Prange´ T 1999 Reactions and rearrangement of triterpenoids – 3-epitaraxerol and its transformation products Indian J Chem 38B:1322– 1330 Downloaded by [Ondokuz Mayis Universitesine] at 09:39 06 November 2014 Natural Product Research 69 Finlay HH, Honda T, Gribble GW, Danielpour D, Benoit NE, Suh N, Williams C, Sporn MB 1997 Novel A-ring cleaved analogs of oleanolic and ursolic acids which affect growth regulation in NRP.152 prostate cells Bioorg Med Chem Lett 7:1769–1772 Honda T, Rounds BV, Bore L, Finlay HJ, Favaloro, Jr, FG, Suh N, Wang Y, Sporn MB, Gribble GW 2000 Synthetic oleanane and ursane triterpenoids with modified rings A and C: a series of highly active inhibitors of nitric oxide production in mouse macrophages J Med Chem 43:4233–4246 Kazakova OB, Giniyatullina GV, Medvedeva NI, Lopatina TV, Baikova IP, Tolstikov GA, Apryshko GN 2014 Synthesis and cytotoxicity of triterpene seven-membered cyclic amines Russ J Bioorg Chem 40:198–205 Laszczyk MN 2009 Pentacyclic triterpenes of the lupane, oleanane and ursane group as tools in cancer therapy Planta Med 75:1549–1560 Liby KT, Sporn MB 2012 Synthetic oleanane triterpenoids: multifunctional drugs with a broad range of applications for prevention and treatment of chronic disease Pharmacol Rev 64:972– 1003 Maitraie D, Hung CF, Tu HY, Liou YT, Wei BL, Yang SC, Wang JP, Lin CN 2009 Synthesis, anti-inflammatory, and antioxidant activities of 18b-glycyrrhetinic acid derivatives as chemical mediators and xanthine oxidase inhibitors Bioorg Med Chem 17:2785–2792 Seo S, Tomita Y, Tori K 1975 Carbon-13 NMR spectra of urs-12-ene and application to structural assignments of components of Isodon japonicus Hara tissue cultures Tetrahedron Lett 1:7–10 Sun H, Fang WS, Wang WH, Hu C 2006 Structure-activity relationships of oleanane- and ursane-type triterpenoids Bot Stud 47:339–368 Tu HY, Huang AM, Wei BL, Gan KH, Hour TC, Yang SC, Pu YS, Lin CN 2009 Ursolic acid derivatives induce cell cycle arrest and apoptosis in NTUB1 cells associated with reactive oxygen species Bioorg Med Chem 17:7265–7274  ... http://dx.doi.org/10.1080/14786419.2014.958737 Application of the taraxerane –oleanane rearrangement to the synthesis of seco-oleanane triterpenoids from taraxerone Phan Minh Gianga*, Vu Minh Trangab, Phan Tong Sona and Katsuyoshi Matsunamic... into new seco-oleanane triterpenoids The application of this method to expand the existing library of synthetic oleananes is the subject of ongoing investigations Supplementary material Synthesis. .. H2O Scheme Synthesis of and from Results and discussion Treatment of taraxerone (1) with m-chloroperoxybenzoic acid (MCPBA) in CH2Cl2 solution at room temperature led to the epoxidation of C-14/C-15