Phytochemistry and biosynthesis of δ-lactone withanolides

Abstract

Withanolides are highly oxygenated natural products. These C 28 steroids with ergostane-based skeletons functionalized at C-22 and C-26 form sixmembered d-lactone rings. Withanolides containing a d-lactone side chain often occur in Solanaceae and have a variety of biological activities because of their complicated structures. Characteristic spectroscopic behaviors and biosynthesis of withanolides are conducive to their structural elucidation and ''biomimetic synthesis'', respectively. However, the last review to summarize their spectroscopic features and biosynthesis was in 1996. Since then, many withanolides with novel structures have been described by their spectra with biosynthesis investigated with many bioassays. This review surveys d-lactone withanolides and emphasizes their spectral features, configurations and biosynthetic genes. The period reviewed includes through January 2014. We also include phytochemical species.

The Integration of Metabolomics and Next-Generation Sequencing Data to Elucidate the Pathways of Natural Product Metabolism in Medicinal Plants

“…In the present review, we will present examples where the application of traditional biochemical and omic-based approaches contributed to new discoveries in the pathways of some secondary metabolites of medicinal importance. We will not cover in detail the knowledge acquired so far on the chemistry of natural products (but we refer the reader to recent excellent reviews on the subject: [13] for benzylisoquinoline alkaloids, [14] and [15] for monoterpenoid indole alkaloids (MIAs), [16] for cannabinoids, [17] for xanthine alkaloids, [18] for ginsenosides, [19] for withanolides, [20] for artemisinin, and [21] for taxol), and we instead focus on the historical developments and the advances made recently in completing the missing parts of the puzzle in the biosynthesis of some important natural products. In the first part of this review, we chose to focus on the cases of benzoisoquinoline alkaloids (BIAs), MIAs, cannabinoids, and caffeine, as they represent exemplary cases of how the application of several approaches, based on the integration of genomics and metabolomics, has helped clarify specific biochemical steps or entire pathway branches that had remained elusive.…”

“…Despite the growing relevance of withanolides in medical research (which we will cover in detail further below), information about their biosynthetic routes and pathway regulation in planta remain scarce. Over the past years, more than 200 different withanolides have been isolated from roots, berries, and leaves of W. somnifera [19]; the focus of most of the pharmacological research was placed, however, almost exclusively on Withaferin A (▶ Fig. 7), the first withanolide to be isolated from W. somnifera [211].…”

UPLC-MS/MS Identification and Quantification of Withanolides from Six Parts of the Medicinal Plant Datura Metel L.

“…These C28 steroids with ergostane based skeletons are functionalized at C-22 and C-26, forming six-membered δ-lactone heterocycles. The complex structural features and excellent biological activities of withanolides have attracted the attention of numerous researchers [1,2].…”

Withanolides from the genus Physalis: a review on their phytochemical and pharmacological aspects

“…Importantly, owing to their diverse and unique structural skeletons, withanolides displayed diverse biological activity, including antimicrobial, anticancer, anti‐inflammatory and immunoregulatory . Therefore, withanolides are regarded to be an important origin of leading compounds and drug candidates, and thus have attracted the interests of chemist and biologist …”

“…In addition, Yang et al . surveyed δ‐lactone withanolides and emphasized their spectral features, configurations, biosynthetic genes, as well as phytochemical species through January 1996 to January 2014 . Last review on the phytochemical progress and the compounds isolated from Physalis over the period from 1995 to 2014 has been published in 2016 …”