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

Abstract

The genus Datura (Solanaceae) contains nine species of medicinal plants that have held both curative utility and cultural significance throughout history. This genus' particular bioactivity results from the enormous diversity of alkaloids it contains, making it a valuable study organism for many disciplines. Although Datura contains mostly tropane alkaloids (such as hyoscyamine and scopolamine), indole, beta-carboline, and pyrrolidine alkaloids have also been identified. The tools available to explore specialized metabolism in plants have undergone remarkable advances over the past couple of decades and provide renewed opportunities for discoveries of new compounds and the genetic basis for their biosynthesis. This review provides a comprehensive overview of studies on the alkaloids of Datura that focuses on three questions: How do we find and identify alkaloids? Where do alkaloids come from? What factors affect their presence and abundance? We also address pitfalls and relevant questions applicable to natural products and metabolomics researchers. With both careful perspectives and new advances in instrumentation, the pace of alkaloid discovery-from not just Datura-has the potential to accelerate dramatically in the near future.

Keywords: Datura; Solanaceae; alkaloid; indole; pyrrolidine; tropane.

Figure 1

Hyoscyamine [(S)-1, the S-enantiomer of atropine, (1) and scopolamine (2), the most well-known alkaloids of the genus Datura.

Figure 2

Flower of D. metel (left) and fruit of D. stramonium var. stramonium (right).

Figure 3

HPLC/ESI-MS base peak intensity chromatogram of a methanol-water extract of three-week-old D. metel root (left) using a C₁₈ LC column on a Waters Xevo G2-XS QToF high-resolution mass spectrometer. The analysis was performed using data-dependent MS/MS in positive-ion mode. (A) Survey scan base peak intensity chromatogram. (B) The survey scan spectrum for hyoscyamine (retention time 10.58 min). (C) MS/MS product ion spectrum for m/z 290 for hyoscyamine shows characteristic monosubstituted tropane alkaloid fragment ions at m/z 142 and 124.

Figure 4

¹H-NMR spectrum (500 MHz, in DMSO-d₆) of scopolamine (2). Indicated peaks correspond to the structural features highlighted in magenta.

Figure 5

Chirality in tropane alkaloids and relationships between meso compounds, enantiomers, and diastereomers for substituted tropanes.

Figure 6

Biosynthesis of tropane and pyrrolidine alkaloids in Datura.

Figure 7

3,7-Disubstituted tropanes found in Datura.

Figure 8

Dehydrotropanes identified in Datura species.

Figure 9

Calystegine, ecgonine alkaloids, and tropane N-oxides found in Datura species. Note that the “pseudo-” nomenclature for ecgonine alkaloids refers to the stereochemistry of the 2-carboxylate, not the 3-hydroxyl.

Figure 10

Cyclic and dimeric tropane alkaloids from Datura.

Figure 11

N-methylpyrrolinium ion (17)-derived pyrrolidine alkaloids.

Figure 12

Indole and beta-carboline alkaloids found in D. stramonium and D. metel.

Figure 13

Miscellaneous alkaloids identified in Datura.