Synthesis of bibenzyl cannabinoids, hybrids of two biogenetic series found in Cannabis sativa

Abstract

Syntheses of a series of compounds which merge a m-dihydroxybibenzyl with a terpenoid structure, giving a series of hybrid cannabinoids in which products of two major biogenetic routes of Cannabis are united, are described. The compounds made are the bibenzyllo-and p-cannabigerols ( 1 9) and (1 8 ) / 0and p-cannabidiols ( 21) and ( 20),/A'-THC ( 22),/A6-THC ( 23),/0-and p-cannabichromenes (25) and (24),/0and p-cannabicyclols (28) and ( 27) and/cannabicitran (26). Chromatographic and spectral data are listed in order t o facilitate search for such 'crossed' types since only the bibenzyl cannabigerols and a chromene have as yet been found in natural sources.The bibenzyllp-cannabigerol ( 1 8 ) has been reported in Helichrysum umbraculigerum (Compositae) and the liverwort Radula variabilis. Our synthetic work confirms the former observation, but the liverwort compound appears to be its o-isomer.The so-called cannabinoid class of natural products found in Cannabis suctira is generally considered to be a biogenetically related group, though actual experimental information is sparse.' Scheme 1 shows the core of the relationships, dealing * Unaware of our earlier work, these compounds have very recently been rediscovered and named canniflavins-h and -B.&

Secondary metabolism in cannabis

“…Moreover, in liverworts from Radula species the isolation of geranylated bibenzyls analogous to CBG was reported (Asakawa et al 1982), suggesting homology of PKS and prenylase genes from the cannabinoid pathway in other species. Crombie et al (1988) reported the chemical synthesis of bibenzyl cannabinoids.…”

Efficient Synthesis of Bibenzyl Derivatives Bearing Pyranyl Moieties: First Total Synthesis of Bauhinol D

“…12 Adduct 11 was confirmed by comparison of its spectral data with those of the known authentic compound. 17 Reactions of 9 with 1-cyclohexene-1-carboxaldehyde and (-)-perillaldehyde in refluxing p-xylene provided adducts 12 and 13 in 60 and 68% yields, respectively, as a single compound, whereas treatment with (-)-myrtenal gave product 14 with 90% diastereoselectivity in 65% yield. The stereochemistry of new compounds 13 and 14 was confirmed by comparison with reported data.…”

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

“…9,10) The structures of the new compounds were determined by careful interpretation of twodimensional NMR spectroscopic data and CD spectral analysis, and those of the known compounds by comparison of their spectral data with those reported in the literature.…”

“…The photochemical reaction product, compound 8, displayed stronger activity than its precursor (6). 9,10) The strong inhibition of the prenylated bisbibenzyls and bibenzyl-cannabinoids (3-8, Fig. 4) was suggested to be due to their antioxidant properties.…”