Erwin Glotter

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.

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.

Synthetic modifications of withanolides with an α-orientated side-chain

In view of the antitumour activity of withanolide E [(20S,22R)-5β,6β-epoxy-14α,17β, 20-trihydroxy 1-oxowitha-2,24-dienolide] and 4β-hydroxywithanolide E, synthetically modified analogues were prepared. In these compounds, the α-orientation of the side-chain was retained. Its degree of bending with respect to the carbocyclic skeleton depends on the presence or absence of the 14α-OH group. Elimination of this group leads to the formation of the 14,20-oxido-bridged and Δ14-compounds. Epoxidation of the latter afforded 14α,15α-epoxides. With the exception of several 5,6-chlorohydrins, most compounds possess an epoxide ring, allylic or homoallylic with respect to the ring A enone.

Withaphysalin C, a naturally occurring 13,14-seco-steroid

The structure of withaphysalin C, a new naturally occurring steroidal lactone of the withanolide group, isolated from Physalis minima(Solanaceae), has been elucidated. This is a 13,14-seco-steroid closely related to withaphysalin A. The lack of a 17α-OH precluded the formation of a 17 → 14 hemiacetal as in the physalins, leading to the alternative formation of a 13 → 14 hemiacetal.

Neighbouring group effects in epoxide ring opening; cis-epoxy-alcohols

The relative importance of polar and steric influences on the course of the acid-catalysed opening of several epoxycholestanes bearing a vicinal cis-hydroxy- or -acetoxy-group has been investigated.

Withanicandrin, a ring-C-substituted withanolide from nicandra physaloides(solanaceae)

The title compound has been shown to be 6α,7α-epoxy-5α-hydroxy-1,12-dioxo-22R-witha-2,24-dienolide. This is the first natural 12-oxowithanolide isolated so far.

Conformational aspects of some 5β-methyl-19-nor-steroids

The stereochemistry of the allylic alcohol (2) and of the epoxy-ketone (3) in the Westphalen-type rearranged steroid series has been elucidated. The n.m.r. spectra of various new and known compounds have been analysed, thus demonstrating the remarkable conformational flexibility of ring B in this series.

Reactions of Nic-1 (nicandrenone), a naturally occurring ring-D-aromatic steroid

Some reactions of Nic-1 (nicandrenone)(2a), the main steroidal component of Nicandra physaloides(Solanaceae), and its relation to the steroidal lactones of the withanolide group are discussed.

An unusual D-homo-rearrangement of a 14α,17β,20α-trihydroxywithanolide. Crystal and molecular structure of 5-hydroxy-14α,17α-epoxy-17β-methyl-5β-D-homoandrostan-1,17a-dione

Cleavage of the C(20)–C(22) bond in a derivative of withanolide E (1), followed by oxidation, afforded the D-homoandrostane derivative (2), whose structure was determined by X-ray analysis; the mechanistic aspects of this unusual rearrangement are discussed.