Isaac Kirson

Constituents of Withania somnifera Dun—XIII : The withanolides of chemotype III☆

Abstract Nine new steroidal lactones of the withanolide series (withanolides E-M) have been isolated from the leaves of Withania somnifera Dun (Solanaceae) growing in the southern coastal plane of Israel. This population of W. somnifera constitutes a new chemotype and is designated as chemotype III. The following structures have been assigned to seven of the above compounds: Withanolide G, 20α-hydroxy-1-oxo-20R,22R-witha-2,5,8(14),24-tetraenolide ( 1 ); withanolide H, 20α,27-dihydroxy-1-oxo-20R,22R-witha-2,5,8(14),24-tetraenolide ( 2 ); withanolide I, 20α-hydroxy-1-oxo-20R,22R-witha-3,5,8(14),24-tetraenolide ( 3 ); withanolide J, 17α,20α-dihydroxy-1-oxo-20S,22R-witha-2,5,8(14),24-tetraenolide ( 4 ); withanolide K, 17α,20α-dihydroxy-1-oxo-20S,22R-witha-3,5,8(14),24-tetraenolide ( 5 ); withanolide L, 17α,20α-dihydroxy-1-oxo-20S,22R-witha-2,5,14,24-tetraenolide ( 6 ); withanolide M, 17α,20α-dihydroxy-1-oxo-14α,15α-epoxy-20S,22R-witha-2,5,24-trienolide ( 7 ).

A chemotaxonomic study of Withania somnifera (L.) dun.

Abstract Three chemical types of Wittania somnifera (L.) Dun., Solanaceae, each containing different steroidal lactones of the withanolide type, have been found to occur in Israel; they have been called types I, II and III. Morphological differences could not be detected between the three types, although each of them has a definite and separate area of distribution. No qualitative ontogenetic changes in the withanolide content could be observed.

The withanolides of Withania somnifera chemotypes I and II

Abstract Seven steroidal lactones of the withanolide series have been isolated as minor constituents of the leaves of Withania somnifera Dun. (Solanaceae) chemotype I , along with the major component withaferin A. Structures have been assigned to the new compounds: withanolide N (17α,27-dihydroxy-1-oxo-20 R ,22 R -witha-2,5,14,24-tetraenolide) ( 6a ) and withanolide O (4β,17α-dihydroxy-1-oxo-20 R ,22 R -witha-2,5,8(14),24-tetraenolide) (7a). Similarly the leaves of W. somnifera chemotype II afforded three new withanolides along with the major component withanolide D ( 9a ) and trace amounts of withanolide G ( 10 ). The new compounds are: 27-hydroxywithanolide D(4β,20α,27-trihydroxy-1-oxo-5β,6β-epoxy-20 R ,22 R -witha-2,24-dienolide) ( 11a ), 14α-hydroxywithanolide D (4β,14α,20α-trihydroxy-1-oxo-5β,6β-epoxy-20 R ,22 R -witha-2,24-dienolide) ( 12 a) and 17α-hydroxywithanolide D (4β,17β,20α-trihydroxy-1-oxo-5β,6β-epoxy-20 S ,22 R -witha-2,24-dienolide) ( 13a ). Whereas all the withanolides of chemotype I are unsubstituted at C-20 (20α-H), those of chemotype II possess an OH at this position (20α-OH).

Constituents of Withania somnifera dun—XI : The structure of three new withanolides☆☆☆

Abstract Three new withanolides (C 28 steroids possessing a 6-membered ring lactone in the side chain) have been isolated from Withania somnifera (Solanaceae) growing in South Africa and characterized as 4β-hydroxy-1-oxo-5β,6β-epoxywitha-2,24-dienolide (IIIa), 4β,20α,( R )dihydroxy-1-oxo-5β,6β-epoxywith-2-enolide (IVa), and 4β-hydroxy-1-oxo-5β,6β-epoxywith-2-enolide (Va). The major steroidal components of the above plant are the known withaferin A (4β,27-dihydroxy-1-oxo-5β,6β-epoxywitha-2,24-dienolide) and withanolide D (4β,20α,( R )-dihydroxy-1-oxo-5β,6β-epoxywitha-2,24-dienolide). The structures assigned to compounds IIIa, IVa and Va are based on spectral evidence (NMR, IR and UV), analysis of their fragmentation under electron impact, as well as on chemical degradation to known compounds.

5,20α(R)-dihydroxy-6α,7α-epoxy-1-oxo-(5α) witha-2,24-dienolide, a new steroidal lactone from withania coagulans

Abstract The structure of the title compound (I) has been elucidated by analysis of the spectral data, as well as by its fragmentation pattern under electron impact. The configuration at C-20 (R) has been determined by NMR, and the one at C-22 (R) is based on CD measurements.

Conformational studies on certain 6-membered ring lactones

Abstract The stereochemistry of 6-membered ring lactones in some naturally occurring steroids has been studied. Circular dichroism measurements in the n → π* band region have shown that one of these lactones (VIb) exists in a half chair conformation, whereas three other lactones (Vb, VII and VIII) are in a half boat conformation. The configuration of the substituents α and β to the lactonic carbonyl has been determined by NMR solvent effects.

Naturally occurring steroidal lactones with a 17α-oriented side chain. Structure of withanolide E and related compounds

Four related steroidal lactones of the withanolide group possessing a 17α-oriented side chain have been characterised as (17S,20S,22R)-5β,6β-epoxy-14α,17,20-trihydroxy-1-oxowitha-2,24-dienolide [withanolide E (1)], (17S,20S,22R)-14α,l7,20-trihydroxy-1-oxowitha-2,5,24-trienolide [withanolide F (2)], (17S,20S,22R)-5α,6β,-14α,17,20-pentahydroxy-1-oxowitha-2,24-dienolide [withanolide S(3)], and (17R,20R,22R)-14α,17-dihydroxy-1-oxowitha-2,5,24-trienolide [withanolide P (4)]. The structure of withanolide E deduced here has been confirmed by X-ray analysis (reported elsewhere); those of withanolide F and S are related to that of withanolide E on the basis of common degradation products. The identification of withanolide P is based on spectral analysis.

New withanolides from a cross of a South African chemotype by chemotype II (Israel) in Withania somnifera

Abstract Three new withanolides have been isolated from hybrids obtained by crossing a chemotype of Withania somnifera received from South Africa and chemotype II originating in Israel. The compounds have been characterized as 4β,20α-dihydroxy-1-oxo-5β,6β-epoxy-20 R ,22 R -witha-24-enolide, 20α-hydroxy-1,4-dioxo-5β,6β-epoxy-20 R ,22 R -witha-2,24-dienolide, and 20α-hydroxy-1,4-dioxo-5β,6β-epoxy-20 R ,22 R -witha-2-enolide. The major steroid of the plant is withanolide D, while the other known withanolides present are 4β,20α-dihydroxy-1-oxo-5β,6β-epoxy-20 R ,22 R ,24 S ,25 R -witha-2-enolide and withaferin A. The structures assigned to the new compounds are based on spectral evidence, analysis of their fragmentation under electron impact, and on chemical correlation with known compounds. The formation of these withanolides in this new hybrid is discussed briefly.

Steroidal constituents of Physalis minima(Solanaceae)

Four new steroidal lactones have been isolated from the leaves of Physalis minima(Solanaceae), along with the known physalin B (1)(major constituent). 5β,6β-Epoxyphysalin B (2b) is a 16α,24-cyclo-13,14-seco-steroid whose structure was established by comparison with the 5α,6α- and 5β,6β-epoxy-derivatives (2a and 6) and obtained by epoxidation of physalin B (1). Withaphysalins A (3) and B (7a) belong to the withanolide group, the first containing an 18,20-lactone and the latter an 18,20-lactol ring. The structure of withaphysalin C, C28H36O7, is still under investigation.

Crystal and molecular structure of withanolide E, a new natural steroidal lactone with a 17α-side-chain

An X-ray analysis, of withanolide E, a new steroidal lactone isolated from Withania somnifera Dun. chemotype III, (14α,17β,20α-trihydroxy-5β,6β-epoxy-1-oxo-17S,20S,22R-witha-2,24-dienolide) has disclosed that the side-chain possesses the unusual 17α-orientation.