Chirality of natural products: hyoscyamine and scopolamine

Monthly changes of the content-ratio between S-(-)- and R-(+)-hyoscyamine as well as those between S-(-)- and R-(+)-scopolamine in the leaves of Datura metel L. cultivated in the field, were quantitatively analyzed by the use of HPLC with a chiral adsorbent. It was found that S-(-)-isomer was predominant for hyoscyamine and the ratio of R-(+)-isomer gradually increased during the growth, whereas in the case of scopolamine, S-(-)-isomer was the sole one found throughout the cultivation period. The 1H-NMR study in the CD3OD solution has suggested that S-(-)-hyoscyamine (1) and S-(-)-scopolamine (2) take a "face-to-face" conformation between their tropane skeletons and the benzene rings of the tropic acid moieties. In the presence of an equimolar NaOD in the CD3OD solution, the racemization at C-2' of 1 and 2 proceeded more rapidly than the hydrolysis at the tropic acid ester bond, presumably due to the steric hindrance caused by their "face-to-face" conformations. In the D2O and H2O solutions, on the other hand, the racemization and the hydrolysis of 1 proceeded smoothly, while those of 2 did not occur. It has been supposed that these individual reaction manners are ascribable in considerable extent to the different basicity of N atom in each tropane skeleton of 1 and 2 and to stronger intramolecular hydrogen bond occurring between the carbonyl oxygen at C-1' and the hydroxyl group at C-3' in the tropic acid moiety of 1.