Δ9-Tetrahydrocannabinolic acid A, the precursor to Δ9-tetrahydrocannabinol (THC)

Abstract

While Δ9-tetrahydrocannabinolic acid A (THCA-A) has been reported to be difficult to crystallize and/or amorphous, we have obtained THCA-A in a pure crystalline form by extraction of marijuana and selective fractionation with liquid CO2. THCA-A (systematic name: 1-hydroxy-6,6,9-trimethyl-3-pentyl-6a,7,8,10a-tetrahydro-6H-benzo[c]isochromene-2-carboxylic acid, C22H30O4) crystallizes in the orthorhombic space group P212121, with Z = 8 and Z′ = 2. The two independent molecules are related by a pseudo-twofold axis centered between the two –CO2H groups, but the conformations of the two –C5H11 chains are quite different (tgt and ttg; t is trans and g is gauche). The carboxylate groups form an intermolecular R 2 2(8) hydrogen-bonded ring; the two C2O2 carboxylate planes are twisted out of the planes of the attached arene rings in opposite directions by 13.59 (8) and 18.92 (8)°, respectively, with a resultant interplanar angle of 28.89 (8)°. Each molecule also has an intramolecular S(6) hydrogen-bond motif between the ortho –OH group and the dihydropyran-ring O atom. Other conformational aspects of the two independent molecules are quite similar to those found in the previously determined structure of THCA-B. THCA-A has shown promise in a number of medical applications. Demonstration of the crystallinity and details of the crystal structure are expected to provide a standard point of departure for chemical and medical experiments.