Synthesis of metabolites of .DELTA.9-tetrahydrocannabinol

Cytochrome P450 enzymes involved in the metabolism of tetrahydrocannabinols and cannabinol by human hepatic microsomes

“…Δ 8 -THC was prepared by acidic isomerization of Δ 9 -THC as described by Gaoni and Mechoulam (1966). 7α-Hydroxy-Δ 8 -THC (Mechoulam et al, 1972), 7β-hydroxy-Δ 8 -THC (Mechoulam et al, 1972), 11-hydroxy-Δ 8 -THC (Inayama et al, 1974), 8β-hydroxy-Δ 9 -THC (Pitt et al, 1975), 9α,10α-epoxyhexahydrocannabinol (9α,10α-EHHC) , 11-hydroxy-Δ 9 -THC (Pitt et al, 1975), 8-hydroxy-CBN (Inayama et al, 1974), 11-hydroxy-CBN (Yamamoto et al, 1987), and 5′-nor-Δ 8 -THC-4′-oic acid methyl ester (Ohlsson et al, 1979) were prepared according to the previous methods. Purities of these cannabinoids prepared were checked to be more than 98% by gas chromatography (GC).…”

Preparation of Racemic, (−)- and (+)-11-Nor-Δ9-Tetrahydrocannabinol- 9-carboxylic Acid

“…Application of the present procedure to (−)-(6a R ,10a R )- 3a then furnished the natural metabolite (−)-(6a R ,10a R )- 2c , spectroscopically identical to authentic material, ,18a while (+)- 3a afforded (+)-(6a S ,10a S )- 2c . Both optical isomers of the metabolite 2c are therefore now available in simple, one-pot syntheses. ,, Additionally, the availability of both (+)- 3a and (−)- 3a should provide an entry into Δ 9 -11-nor-9-substituted or Δ 9 -11-substituted THC derivatives of both unnatural (6a S ,10a S ) and natural (6a R ,10a R ) configuration.…”

“…Workup up then gave a light yellow oil which was subjected to MPLC on silica (CHCl 3 gradient to 95:5 CHCl 3 /MeOH) to give the crude acid (17 mg, 50%) as a light yellow oil. Rechromatography (silica, 98:2 CHCl 3 /MeOH) provided (6a R ,10a R )- 2c as a white crystalline solid: mp 206−209 °C (subl ∼170 °C) (lit . 205−207 °C); [α] 25 D = −169 ( c 0.15, CHCl 3 ) 25 (authentic material,18a [α] 25 D = −164 ( c 0.15, CHCl 3 ); 1 H NMR identical 25 to those of (±) and of authentic material. ,18a IR (KBr) 3700−2400 (br), 1681 (s), 1626 (s) cm -1 ; 13 C NMR δ 14.03 (q), 19.15 (q), 22.54 (t), 24.21 (t), 25.15 (t), 27.55 (q), 30.65 (t), 31.48 (t), 34.64 (d), 35.48 (t), 44.20 (d), 77.19 (s), 106.70 (s), 107.56 (d), 110.30 (d), 128.31 (s), 143.50 (s), 144.95 (d), 153.95 (s), 154.96 (s), 170.89 (s); MS (+)-FAB m / z 345 [M·H] + , 343 [M − H], 329, 327, 299; HRMS (+)-FAB calcd for C 21 H 29 O 4 [M·H] + 345.2066, found 345.2077.…”

A urinary metabolite of Δ1-tetrahydrocannabinol. The first synthesis of 4′′-hydroxy-Δ1-tetrahydrocannabinol-7-oic acid labelled with deuterium

“…The aldehyde (11) was oxidized using N a C l e in the presence of 2-methyl-2-butene as a hypochlorous scavenger using the method for oxidation described by Siege1 ef al. [26], followed by hydrolysis under alkaline conditions [27] The mass spectral analysis of the silylated methyl ester of 14, see figure 3, gives a molecular ion at m/z 524. Other diagnostic fragments are m/z 465 and 434 corresponding to and [M+-HOTMS] .…”