Isolation, Structural Elucidation and Bioactivity Studies of Tropane Derivatives of Alkaloids from Seeds Extract of Datura Stramonium

Alkaloids of the Genus Datura: Review of a Rich Resource for Natural Product Discovery

“…Liu and colleagues [47] purified four indole alkaloids (3-6, Figure 12) from D. metel using silica gel column chromatography (eluting with chloroform/methanol), followed by preparative C 18 HPLC and Sephadex column chromatography, to yield the indole alkaloids in 96.4-97.8% purity, although the yield was very low-only milligram quantities of the alkaloids were isolated from 7 kg of D. metel seeds. Welegergs et al [48] purified a trisubstituted tropane alkaloid (β-7) from D. stramonium seeds using a combination of silica gel chromatography and preparative TLC; Siddiqui and co-workers similarly used preparative TLC (chloroform/ether) to isolate the nonpolar benzoyltropane datumetine (8) from D. metel, which they then recrystallized as a high-purity hydrochloride salt [45]. In a unique example of column chromatography, Beresford and Woolley first used a column of Kieselguhr (diatomaceous earth) buffered with phosphate (pH 6.8) to fractionate D. ceratocaula aerial part extract into three "bases" when eluting with light petrol followed by ether; alkaloid 8 (SI Table S1) was isolated from one fraction [49].…”

“…Additional information about the structure (such as the presence of methines indicative of a tropane bridgehead (2-and 5-positions) and the para-methoxyl group was revealed by DEPT. Similarly, Welegergs and colleagues isolated a trisubstituted tropane alkaloid from Ethiopian D. stramonium seeds (β-7), and they used a similar combination of 1 H, 13 C, and DEPT-135 NMR experiments to assign the structure of the isolated alkaloid as 7 (SI Table S3) [48]. Liu and co-workers utilized 1 H-1 H COSY and 1 H- 13 C-HMBC, and 1 H- 13 C-HSQC, in addition to 1 H and 13 C-NMR, to establish connectivity of the atoms in the daturametelindole alkaloids (3-6) isolated, obviously, from D. metel), several of which possess a unique spirocyclic oxindole core [47].…”

“…The structure was proposed on the basis of a) loss of formaldehyde by McLafferty rearrangement (consistent with tropic acid derivatives), and b) loss of 72 Da corresponding to the propenyloxy group. Welegergs et al [48] isolated 3-(3'-methoxytropoyloxy)-6-tigloyloxy-7-hydroxytropane (β-7) and assigned its structure by NMR. The 3-position stereochemistry for this alkaloid is drawn as β, although the report does not specify how this assignment was confirmed, nor is the stereochemistry of the tropic acid side chain explicitly specified.…”

“…Nonetheless, many modern studies on the medicinal properties of Datura still employ whole-plant part extracts, and comparatively little is known about the active alkaloidal constituents beyond atropine and scopolamine-two alkaloids out of potentially hundreds across the genus, where there is a plethora of interesting bioactivity waiting to be discovered. In addition to their anticholinergic and psychoactive activity, some tropane alkaloids have shown antiviral, antifungal, and antimicrobial properties, while others can reverse multidrug resistance in cancer cells [48,160,161], while the pyrrolidine, indole, and beta-carboline alkaloids are also largely unexplored. More screening of isolated Datura alkaloids against diverse targets should be performed, and as their structures are elucidated, it will become easier to perform structure-activity relationship studies and design novel semi-synthetic or synthetic alkaloid mimics.…”