Cannabichromene homologs, analogs, and isomers as well as the CI-homolog and isomer of cannabigerol were prepared and tested for their antimicrobial and antifungal properties. Spectral data of all compounds synthesized are presented.
Keyphrases 0 Cannabichromene-analogs, synthesis and antimicrobial activities of related compounds, cannahigerol 0 Antimicrobial activit iea -cannahichromene and cannahigerol, analogs. synthesis and related compounds o Analogs-cannabichromene and cannahigerol, synthesis and antimicrobial activities of related compounds Different cannabinoids have been isolated from Cannabis satiua L. (1). Most of the biological studies carried out concentrate on the major psychoactive constituent A9-tetrahydrocannabinol and its isomers (2-4). However, little attention has been given to the biological activity of cannabichromene (I) because of its relatively low concentration in the plant material.
Recently, a procedure was developed for the synthesis of I in high yield (60%) (5), which made the material available for pharmacological testing.
T h e biological activities of cannabichromene has been reported (6-9), as well as its homologs and isomers (10,ll). This paper describes the synthesis and antimicrobial activities of cannabichromene homologs, analogs, and iso- mers and that of cannabigerol-C1, isocannabigerol-CI, and tetrahydrocannabigerol-C1.
EXPERIMENTAL
Melting points' were determined in open glass capillary tubes and are uncorrected. Proton nuclear magnetic resonance ('H-NMH) spectra2 were recorded in deuterochloroform or in deuteromethanol using tetramethysilane as the internal standard. 1R spectra? were recorded in liquid film, chloroform, or in potassium bromide pellets. Mass spectra' were recorded at an electron energy of 70 eV. UV spectra5 were recorded in met.hano1. ':C-NMH spectra" were recorded in deuterochloroform or deu teromethanol.
Biological Activities-Antibacterial and Antifungal Activities-All compounds were t.ested for activity against Gram-positive, Gram-negative, and acid-fast bacteria and selected fungi. A qualitative screen was performed on all compounds, while quantitative assays were done on active compounds only. Routine qualitative screens were carried out using the agar well diffusion assay a s previously described ( 12). Minimum inhibitory concentrations were determined using the twofold (hroth) serial dilution method (12) with a concentration of 100pg/ml in the first tube. Streptomycin sulfate was used as a positive control for antibacterial activity, while amphotericin โฌ3 was used as a n antifungal positive control.
2-Methyl-2-(4'-methylpent-3'-enyl) -5 -hydroxy-7-methylchromene (II)-Orcinol(3.45 g, 0.028 mole) was dissolved in 55 ml of toluene with heating and stirring. Equimolar quantities of tert-butylamine were I Thomas Hoover Unimelt.
JEOI, C-6OHL. l'erkm-l.:lmer 267.
Finnigan 8200, MS/DS system. ,' Heckrnan Acta 111.
.JEOL FX-60 operating at 15.03 MHz added to the resulting solution followed by dropwise addition of citral.
T h e reaction mixture was refluxed for 9 hr. The mixture was then cooled to room temperature, transferred to a round-bottom flask, and the solvent evaporated. GC analysis of the reaction mixture showed 48.3?k conversion to 11. About one half of the crude reaction product (5 g) was applied over a dry packed silica gel 60 column (100 g) using 15 ml of cyclohexanechloroform ( l : l ) , and elution was continued with the same solvent.
Fractions of 25 ml were collected and combined based on TLC similarities. Fractions containing 11 (1.96 g) weie rechromatographed as before to yield I1 of >95% purity as light brown oil. UV A, , , (methanol) nm (log 0: 229 (4.38) and 280 (3.92); IR (liquid film) major bands a t 3400,2970,