Crystal structure of 4-[(adamantan-1-yl)amino]-naphthalene-1,2-dione.

The title compound, C20H21NO2, an example of a stable 1,2-naphtho-quinone, was determined by single-crystal X-ray diffraction analysis at 100 K. This structure illustrates steric buttressing of the adamantanyl group, forcing the N-H group into the coplanar aromatic C-H. The presence of strong delocalization between the planar N atom at the 4-position and the carbonyl group at the 2-position is indicated. In the crystal, C-H⋯O and C-H⋯π inter-actions link the mol-ecules into a three-dimensional network.

Crystal structure of (E)-2-(tert-butyl-amino)-4-(tert-butyl-imino)-naphthalen-1(4H)-one.

The title compound, C18H24N2O, is the first example of a naphtho-quinone imine derivative isolated in the 4-imine/2-amine tautomeric form having bulky alkyl substituents at the N atoms. The mol-ecular conformation is stabilized by an intra-molecular hydrogen bond between the amine and a carbonyl group and by London attraction between the two tert-butyl groups. Only van der Waals inter-actions were identified in the crystal packing.

Cytochrome P450 3A Enzymes Catalyze the O6-Demethylation of Thebaine, a Key Step in Endogenous Mammalian Morphine Biosynthesis.

Morphine, first characterized in opium from the poppy Papaver somniferum, is one of the strongest known analgesics. Endogenous morphine has been identified in several mammalian cells and tissues. The synthetic pathway of morphine in the opium poppy has been elucidated. The presence of common intermediates in plants and mammals suggests that biosynthesis occurs through similar pathways (beginning with the amino acid L-tyrosine), and the pathway has been completely delineated in plants. Some of the enzymes in the mammalian pathway have been identified and characterized. Two of the latter steps in the morphine biosynthesis pathway are demethylation of thebaine at the O(3)- and the O(6)-positions, the latter of which has been difficult to demonstrate. The plant enzymes responsible for both the O(3)-demethylation and the O(6)-demethylation are members of the Fe(II)/α-ketoglutarate-dependent dioxygenase family. Previous studies showed that human cytochrome P450 (P450) 2D6 can catalyze thebaine O(3)-demethylation. We report that demethylation of thebaine at the O(6)-position is selectively catalyzed by human P450s 3A4 and 3A5, with the latter being more efficient, and rat P450 3A2. Our results do not support O(6)-demethylation of thebaine by an Fe(II)/α-ketoglutarate-dependent dioxygenase. In rat brain microsomes, O(6)-demethylation was inhibited by ketoconazole, but not sulfaphenazole, suggesting that P450 3A enzymes are responsible for this activity in the brain. An alternate pathway to morphine, oripavine O(6)-demethylation, was not detected. The major enzymatic steps in mammalian morphine synthesis have now been identified.