New Bibenzyl Cannabinoid from the New Zealand Liverwort Radula marginata.

Abstract

We are continuing the chemosystematic study of the liverworts by gas chromatography (GC)-and liquid chromatography (LC)-MS analysis, as resolution of the relationships between species of liverworts is difficult because of their small size, and ephemeral nature of the sporophytic generation, which yields many conventionally critical taxonomic characters. This is particularly true of the genus Radula. This investigation is part of a chemosystematic study devoted to assisting the resolution of infrageneric relationships within Radula. During our investigation of the genus of Radula, we found the cannabinoid type compound, perrottetinene in the Japanese liverwort, Radula perrottetii.1) Radula species are very rich sources of aromatic compounds and are extremely rich in prenylated bibenzyls.2-4) The ether extract of the New Zealand liverwort R. marginata, which have not yet been investigated phytochemically, afforded new cannabinoid type and prenylated bibenzyls.The ether extract of R. marginata was chromatographed on silica gel to give three new aromatic compounds 1, 3 and 4, together with known 2, 5, 6 and d-tocopherol (Fig. 1 Hz, H-5Љ, 7Љ) were observed in the 1 H-NMR spectrum of 1, due to a 1-substituted aromatic ring. A fragment peak, tropylium cation (C 7 H 7 ϩ ) at m/z 91 in the electron impact (El)-MS of 1 provided further evidence for this aromatic ring. The EI-MS spectrum of 1 showed a molecular ion peak at m/z 392, its constitution of C 25 H 28 O 4 was confirmed by its high resolution EI-MS measurement. Analysis of the heteronuclear multiple quantum coherence (HMQC) and heteronuclear multiple bond correlation (HMBC) spectra (important correlations are summarized in Fig. 2) supports the structural assignment. The nuclear Overhauser enhancement spectroscopy (NOESY spectrum of 1 (Fig. 3) showed correlations between H-3 and 4, confirming the stereochemistry of a cis-fused ring. Consideration of these spectral data led to the conclusion that the compound was perrottetinenic acid (1), although its absolute configuration remains to be clarified. It is noteworthy that in this investigation the GC-MS analysis of 1 showed a same retention time and mass spectrum as those of 2 because of decarboxylation of 1 in an injection at 250°C of GC.Compound 3 was isolated as a minor constituent of this species, the coloration of which showed dark blue with spray of FeCl 3 on a TLC. The presence of a phenolic hydroxyl group was anticipated. The structure of 3 was deduced by comparing its spectral data with those of 2. Whereas the car-* To whom correspondence should be addressed. e-mail: toyota@ph.bunri-u.ac. The ether extract of the New Zealand liverwort Radula marginata afforded a new cannabinoid type bibenzyl compound named perrottetinenic acid, and two new bibenzyls, together with a known cannabinoid, perrottetinene. Their structures were established by two dimensional (2D) NMR spectral data. The structure of perrottetinenic acid was a similar to that of D D 1 -tetrahydrocannabinol, a known hallucinogen. Cannabinoid type bibe...

Concise Synthesis of (±)-Perrottetinene with Bibenzyl Cannabinoid

“…[8][9] In conclusion, biologically interesting (±)-perrottetinene with bibenzyl cannabinoid structure was efficiently and concisely synthesized from the readily available dihydropinosylvin in an overall yield of 45% (3 steps).…”

“…Structurally related perrottetinene (4) and perrottetinenic acid (5) with a bibenzyl cannabinoid nucleus were isolated from the extract of the New Zealand liverwort Radula marginata (Figure 2). 8 The structures of these natural products were determined using spectroscopic analysis. 8 Interestingly, most of the naturally occurring tetrahydrocannabinols 1-3 possessed a trans-fused ring junction between cyclohexene (or cyclohexane) and the pyranyl ring, whereas perrottetinene (4) and perrottetinenic acid (5) exhibited a cis-stereochemisty.…”

“…8 The structures of these natural products were determined using spectroscopic analysis. 8 Interestingly, most of the naturally occurring tetrahydrocannabinols 1-3 possessed a trans-fused ring junction between cyclohexene (or cyclohexane) and the pyranyl ring, whereas perrottetinene (4) and perrottetinenic acid (5) exhibited a cis-stereochemisty. Although the total synthesis of perrottetinene (4) has already been reported in a 9-step process, 9 simple and more concise synthetic approaches are still needed.…”

Chemical Constituents of Malagasy Liverworts, Part V: Prenyl Bibenzyls and Clerodane Diterpenoids with Nitric Oxide Inhibitory Activity from Radula appressa and Thysananthus spathulistipus

“…1,[6][7][8] The present paper deals with the isolation and structural determination of two clerodane diterpenes (1, 2), prenylated bibenzyls, and their rearranged products (3)(4)(5)(6)(7)(8) from T. spathulistipus and R. appressa, respectively, as well as their nitric oxide (NO)-inhibitory properties in lipopolysaccharide (LPS)-induced RAW 264.7 cells. To the best of our knowledge, this is the first report on the phytochemical investigation of the two liverwort species.…”

Bazzanane Sesquiterpenoids from the New Zealand Liverwort Frullania falciloba

“…3) We have previously reported several peculiar terpenoids and aromatic compounds from some liverworts endemic to New Zealand. [4][5][6][7][8] These terpenoids and aromatic compounds are chemosystematically specific to liverworts and are used as genetic markers for the species.…”