Enantiospecific Total Syntheses and Assignment of Absolute Configuration of Cannabinol‐Skeletal Carbazole Alkaloids Murrayamines‐O and ‐P

Abstract

First enantiospecific total syntheses of the cannabinol-skeletal carbazole alkaloids murrayamines-O and -P isolated from root barks of Murraya euchrestifoli, have been accomplished by highly diastereoselective, Lewis acid catalyzed coupling reactions of commercially available monoterpenes with carbazole derivative, which in addition to confirming the structure also established the absolute configuration of the natural products. Synthesis of both natural products and their enantiomers was achieved with high atom economy, in a protecting-group free manner and in six steps longest linear sequence from commercially available aniline derivative and verbenol.

Synthetic pathways to tetrahydrocannabinol (THC): an overview

“…Recently, Dethe and co-workers also demonstrated the use of (−)-verbenol (10) in the synthesis of phytocannabinoids . 21 Previous reports showed that BF 3 -mediated activation of verbenol leads to the thermodynamic Δ 8 -isomer. 18 In this synthesis, however, the authors describe that with small amounts of BF 3 •OEt 2 and short reaction times the kinetic Δ 9isomer was obtained.…”

Trends in carbazole synthesis – an update (2013–2023)

“…[185][186][187] Although the absence of an aryl-halide bond can lead to regioselectivity issues in the coupling process, the comparatively mild reaction conditions, facile operational set-up and wide functional group tolerance have enabled the total synthesis of a wide array of naturally occurring carbazoles. A representative selection of successfully completed total synthesis is shown in Scheme 26, [188][189][190][191][192][193] with Scheme 24 Formal nitrogen-iodine exchange on diaryliodinium salt for the synthesis of Carprofen.…”

“…185–187 Although the absence of an aryl–halide bond can lead to regioselectivity issues in the coupling process, the comparatively mild reaction conditions, facile operational set-up and wide functional group tolerance have enabled the total synthesis of a wide array of naturally occurring carbazoles. A representative selection of successfully completed total synthesis is shown in Scheme 26, 188–193 with the Knölker group being a main contributor in this field. 194–210,211,212 Mechanistically, the carbon–carbon bond formation is initiated by two sequential electrophilic attacks of the palladium catalyst on diarylamine 82 , generating six-membered palladacycle 84 .…”

Light-Promoted Low-Valent-Tungsten-Catalyzed Ambient Temperature Amination of Boronic Acids with Nitroaromatics

“…3-Methoxy-4-methyl-N-phenylaniline (3q). 29 Column chromatography (petroleum ether/CH 2 Cl 2 = 100:1 to 30:1; silica gel, 100− 200 mesh); white solid (31.1 mg, 73% yield). 1 H NMR (400 MHz, chloroform-d) δ 7.28−7.23 (m, 2H), 7.07−7.01 (m, 3H), 6.93−6.88 (m, 1H), 6.62 (d, J = 7.0 Hz, 2H), 5.66 (br s, 1H), 3.79 (s, 3H), 2.18 (s, 3H).…”