New ent-Verticillane Diterpenoids from the Japanese Liverwort Jackiella javanica

Abstract

In our search for novel compounds possessing biological activity, we are currently studying the chemical constituents of Japanese, European, New Zealand and Argentine liverworts.1,2) To date, we have reported a number of novel carbon skeletal, sesqui-and diterpenoids or bisbibenzyl compounds, and enantiomers of known terpenoids. Some of them show interesting biological activities.3) Moreover these compounds are often valuable as chemosystematic and genetic markers. 1,2)The sesqui-and diterpenoids of Jackiella javanica SCHIFFN., that is known as only one genus and one species in Japan, have previously been reported by our group. 4,5) Reinvestigation of the Japanese J. javanica resulted in the isolation of the very rare natural products, ent-verticillane diterpenoids 1-8 as main components, together with known sesquiterpenoids and ent-kaurane diterpenoids. 6) Recently, Coates et al. 7) reported that the absolute configuration of (ϩ)-verticillol which had been isolated from Sciadopitys verticillata 8) should be corrected from structure 9 to 1 by X-ray crystallographic analysis of the p-iodobenzoate derivative. Inevitably, the absolute configuration of ent-verticillol, the enantiomer of (ϩ)-verticillol, must be corrected from structure 1 to 9. Furthermore, the absolute structures of the other ent-verticillanes might also be reversed. Continuing the study of the chemical constituents of J. javanica resulted in the isolation of three additional new ent-verticillanes 10-12, together with the four known sesquiterpenoids 13-16 and a known ent-verticillene diterpenoid 17.Here, we report on the isolation and structural characterization of the new compounds from J. javanica and revision of their absolute configurations. Results and DiscussionA combination of chromatography on silica gel, Sephadex LH-20 and preparative HPLC of the ether extract of J. javanica afforded three new ent-verticillanes 10-12 as well as known sesquiterpenoids, ent-ledene (13), 9) ent-4,10-aromadendrandiol (14), 10) (1R,7R)-germacra-4(15),5E,10(14)-trien-1-ol (15) 4) and ent-11-hydroxy-5-guaien (16), 11) and a diterpene hydrocarbon, ent-exo-verticillene (17). [12][13][14] The structures of the known compounds were determined by comparison of authentic 1 H-and 13 C-NMR spectra and/or reference data.The IR spectrum of compound 10 showed the presence of hydroxy and carbonyl groups (3466, 1709 cm Ϫ1 ). Electron impact mass spectrometry (EI-MS) showed a molecular ion peak at m/z 304 [M] ϩ and the molecular formula was confirmed as C 20 H 32 O 2 by high resolution EI-MS (HR-EI-MS). The 1 H-NMR spectrum (Table 1) (Table 2) and distortionless enhancement by polarization transfer (DEPT) spectra indicated the presence of two trisubstituted olefinic carbons (d 124.3, 128.9 each CH, 132.9, 134.3 each C), a carbonyl carbon (d 205.7) originating from the aldehyde group, a quaternary carbon (d 76.6) bearing a hydroxy group, and also four methyls, seven methylenes, two methines and a quaternary carbon. These spectral data are similar to those of verticillene-type...

Oxygenated verticillene derivatives from Bursera suntui

“…Previously, several epoxyverticillanes were obtained by oxidation of verticillenes with peroxyacids, such as m-chloroperoxybenzoic acid (Nagashima et al, 2005) and monoperphthalic acid (Karlsson et al, 1978), or by treatment with H 2 O 2 and SeO 2 in t-BuOH (Cerda- García-Rojas et al, 2007). Finally, allylic alcohols 9-11 are relevant because they closely resemble some structural features of the cytotoxic verticillenes cespitularins C and E isolated from the soft coral Cespitularia hypotentaculata (Duh et al, 2002).…”

“…These metabolites have been isolated from diverse sources such as the conifer Sciadopitys verticillata (Karlsson et al, 1978), the yew trees Taxus canadensis (Zamir et al, 1995(Zamir et al, , 1998, T. cuspidata (Renzulli et al, 2004), T. chinensis (Fang et al, 1995), T. chinensis var. mairei (Shi et al, 1998), and T. mairei (Shi et al, 2005), as well as the soft corals Cespitularia hypotentaculata (Duh et al, 2002) and C. taeniata (Shen et al, 2005), antipodal structures have also been found in the liverworts Jackiella javanica and Jungermannia infusca (Nagashima et al, 1997(Nagashima et al, , 2005. Some verticillene derivatives display relevant biological activity against diverse tumour cell lines; for example, verticillenes isolated from Taxus sp.…”

Volatile Components from Selected Tahitian Liverworts

“…This phenomenon also concerns verticillane-type diterpenoids. Up to now only one liverwort was known for the presence of ent-verticillanes [18,19]. In this paper we record two other liverworts, C. hirtellus and an unidentified Jungermannia species, which also biosynthesize such compounds, together with cembranoids.…”

“…Interestingly, this liverwort produces ent-verticillol (11) and ent-epiverticillol (12). Until this finding, ent-verticilane-type diterpenoids had been found only in Jackiella javanica (Jackiellaceae) [18,19]. The verticillane and cembrane diterpene skeletons can be considered as biogenetically related and it was suggested that both have a common biogenetic precursor [20,21].…”

Therapeutic potential of bryophytes and derived compounds against cancer

“…cordifolia [101] , Jungermannia rotundata [102] , Jungermannia hattoriana [103] , Jungermannia infusca [104][105][106] , Jungermannia subulata (cell suspension culture) [107] , Jackiella javanica [108,109] , Pellia endiviifolia [110] , P. perrottetiana [111] , …”