New Withanolides and Other Constituents from the Fruit of Withania somnifera

Abstract

Two new steroidal lactones of the withanolide‐type, 5β, 6α, 14α, 17β, 20β‐pentahydroxy‐1‐oxo‐20 S, 22R‐witha‐2, 24‐dienolide (1)and 6α, 7α‐epoxy‐5α, 14α, 17α, 23β‐tetrahydroxy‐1‐oxo‐22R‐witha‐2, 24‐dienolide (2), were isolated from the fruit of Withania somnifera (L.) Dunal (Solanaceae) growing in Southern Egypt, together with two known coumarins, scopoletin (3)and aesculetin (4), a known triterpene, viz. β‐amyrin (5), and two known phytosterols, viz. stigmasterol (6) and sitosterol (7). The structures of the isolated compounds have been elucidated by spectroscopic methods including UV, IR, 1H‐, 13C‐NMR, DEPT experiments, HRFAB‐, FAB‐, and EI‐mass spectrometry. The in vitro antimicrobial activity of the new withanolide (1) and the alcoholic fruit extract are discussed.

Withanolides and Related Steroids

“…One of the most common variations in the withaferin A substitution pattern is the hydrolytic cleavage of the 5,6-epoxide according to the F€ urst-Plattner rule (16), to give the trans-diaxial 5a,6b-diol as in coagulin H (7) and coagulin S (8) isolated from W. coagulans (17,18). A less common cleavage is that occurring in a transdiequatorial manner, as found in 9 and 10 (14), later reported as new by Kuroyanagi et al (19), and in 4-deoxywithaperuvin (11) (20). Compound 12 represents an unusual variant of the above, with a 3a,6a-epoxy bridge (21), which could derive from the cyclization of 10 also present in the same extract.…”

“…In the case of 13 the configuration of the hydroxy group at C-16 was not determined (15 The 5a-hydroxy-6a,7a-epoxy substitution pattern is also a common arrangement found in W. somnifera withanolides. Simple variations arising from the combination of hydroxy substituents at both typical positions (C-14, C-17, C-20) and some less common ones such as C-16 or C-23 are observed in withasomniferols A (15) and B (16) (24), 14a,17a-dihydroxywithanolide R (17) (20), isowithanone (18) (25), and the 16b-acetate 19 (26). Withasomniferol B (16) is a stereoisomer of the known ixocarpanolide, although the configurations at positions 24 and 25 were not specified.…”

“…4-Deoxywithaperuvin (11) was moderately active against several Gram-positive (B. cereus, B. subtilis, Streptomyces spp. ), and Gram-negative (Pseudomonas fluorescens, Serratia marcescens) bacteria, but inactive against Micrococcus luteus, M. roseus and S. aureus; antifungal activity was poor (20). On the other hand, the 18-oxygenated withanolides 18-acetoxywithanolide D (142) and its D 5 analogue 495 from D. brachyacantha were active against S. aureus and B. subtilis and inactive against E. coli and Shigella flexneri (84).…”

Potent lipid peroxidation inhibitors from Withania somnifera fruits

“…8 Our recent study on the leaves of this plant yielded several withanolides with cyclooxygenase enzyme inhibitory activity. 9 Also, unsaturated fatty acids 10 -12 and withanolides 13,14 were reported from the seeds of W. somnifera. However, the components of W. somnifera fruits were not investigated for biological activities.…”

A Review on Adaptogenic Activity of Ashwagandha (Withania Somnifera): An Ayurvedic Appraisal

“…20 . Steroidal lactones are present in leaves, commonly called withanolides with C28 steroidal nucleus and C9 side chain, with a six membered lactone ring 21 . Withaferin A and withanolide D which are two main withanolides, attributes to have much pharmacological action.…”