6-methoxydihydrosanguinarine and sanguinarine

All the enantiomers of methoxydihydrosanguinarine (MS), ethoxydihydrosanguinarine (ES) and iso-propoxydihydrosanguinarine (PS) were separated by chiral HPLC. They were further identified by comparing the retention times of authentic standards as well as LC-MS. Interestingly, the approximately same conversion rates for the formation MS from ES or PS and the slower conversion of MS in isopropanol compared to ethanol demonstrated two step mechanism in the reaction of alkoxysanguinarine in alcohols, which is composed of the initial formation of sanguinarine as a planar intermediate and the addition of alcohol to intermediate as possible rate limiting step. Thus, sanguinarine has a pivotal role in the chemical behavior of alkoxysanguinarine in alcoholic solvents. Such possible variation of the structure of sanguinarine may be the source of its diverse biological activities.

Topics: Alcohols; Benzophenanthridines; Chromatography, High Pressure Liquid; Isoquinolines; Solvents; Stereoisomerism

A biologically active benzophenanthridine alkaloid, 6-methoxydihydrosanguinarine (MS), was isolated from Hylomecon plants. Although enantiomers of MS can be separated by chiral HPLC, its isomers rapidly form a racemic mixture in methanol. The rate constants for the racemization of MS enantiomers were 9.20x10(-4)s(-1) and 9.95x10(-4)s(-1) for (+)-MS and (-)-MS, respectively, as determined by dynamic HPLC and chiral chromatography. This unusually rapid racemization may originate from the formation of a stable iminium ion intermediate, sanguinarine. Therefore, the variety of biological activities exhibited by MS may be attributable to a combination of (+)-MS, (-)-MS, and sanguinarine.

Topics: Benzophenanthridines; Chemistry, Pharmaceutical; Chromatography, High Pressure Liquid; Isoquinolines; Methanol; Papaveraceae; Plant Extracts; Solvents; Stereoisomerism