Structural/Physicochemical Properties of Corycavidine, a Key Intermetabolite in the Biosynthesis of Isoquinoline Alkaloids, Elucidated by X-Ray Crystallography, Solution Conformation and Thermal Behavior Analyses, and Energy Calculations

The conformational/physicochemical features of corycavidine (1), 5,7,8,15-tetrahydro-3,4-dimethoxy-6,15-dimethyl-[1,3]benzodioxolo[5,6-e] [2]benzazecin-14(6H)-one, an important protopine-type alkaloid that serves as the key intermetabolite in the biosynthesis of isoquinoline alkaloids, were examined by X-ray crystallography, 1H NMR spectroscopy, as well as thermal analysis and energy calculations. Two stable conformations of 1, as proposed by energy calculations, were also observed in both the crystalline and solution states. Racemization of optically active 1, which was caused by heating of the crystal, was analyzed by differential-scanning calorimetry. By taking advantage of the H-2H replacement reaction at the C13 atom of 1, the rate of racemization in the C2H3O2H/NaO2H solution was measured as a function of the temperature; the energy barrier between both enantiomers was estimated to be 4.7 kcal mol-1. The crystallization of racemic 1 led to two different crystal forms, i.e., the racemic crystal and t...