The structure of a new prenylated coumarin (E-omega-benzoyloxyferulenol, 1b) from the Sardinian giant fennel (Ferula communis) has been confirmed by synthesis. The parent compound ferulenol (1a) showed sub-micromolar antimycobacterial activity, which was partly retained in 1b and in the simplified synthetic analogue 3, but diminished in its omega-hydroxy and omega-acetoxy derivatives (1c and 1d, respectively). The outstanding activity of 1a, its low toxicity, and the evidence for definite structure-activity relationships make this prenylated 4-hydroxycoumarin an interesting antibacterial chemotype worth further investigation.
Cannabitwinol (CBDD, 3), the second member of a new
class of dimeric phytocannabinoids in which two units are connected
by a methylene bridge, was isolated from a hemp (Cannabis
sativa L.) industrial extract. The structural characterization
of cannabitwinol, complicated by broadening of 1H NMR signals
and lack of expected 2D NMR correlations at room temperature, was
fully carried out in methanol-d
4 at −30
°C. All the attempts to prepare CBDD by reaction of CBD with
formaldehyde or its iminium analogue (Eschenmoser salt) failed, suggesting
that this sterically congested dimer is the result of enzymatic reactions
on the corresponding monomeric acids. Analysis of the cannabitwinol
profile of transient receptor potential (TRP) modulation evidenced
the impact of dimerization, revealing a selectivity for channels activated
by a decrease of temperature (TRPM8 and TRPA1) and the lack of significant
affinity for those activated by an increase of temperature (e.g.,
TRPV1). The putative binding modes of cannabitwinol with TRPA1 and
TRPM8 were investigated in detail by a molecular docking study using
the homology models of both channels.
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