Withanolides structures

A group of withanolides structurally related to trechonolide A (64), have been subsequently isolated from different Solanaceae. From J. magellanica (Punta Arenas, Chile) were isolated (-)-jaborotetrol (65), (-)-jaborolone (66), (+)-jaborochlorotriol (67) and (-)-jaborochlorodiol (68)... 

In 2007, Christen and co-workers65 reported the elucidation of the structures of a series of withanolides from the leaves of Withania adpressa, a plant endemic to the Sahara of Morocco and Algeria. The observed INADEQUATE correlations for one of the molecules characterized are shown on 16. The data were recorded at 600 MHz but unfortunately no further experimental details were reported. It is also interesting to note that there were no correlations reported involving the 11- and 12-posi-tions in the C-ring of the steroid nucleus. 

Within the cucurbitacins and withanolides it has been found that certain structural analogues possess agonistic rather than antagonistic activity hexanorcucurbitacin D (EC50 = 2.5 x 10 5M) and withaperuvin D (EC50 = 2.5 x 10 5M) [170], In the case of hexanorcucurbitacin D, this concurs with the hypothesis that antagonistic activity of cucurbitacins is associated with the presence of an a,(3-unsaturated ketone in the side-chain [205], which hexanorcucurbitacin D lacks. 

Figure 7.6 Structures of the withanolides (14), cardiac glycosides (15) and limonoids (16).

Electrophilic Addition.—Reactions of androsta-3,5-dienes with MCPBA gave complex mixtures the composition of which was dependent upon the level of peracid used (1 or 2 equivalents). Diepoxides were isolated in low yield only when 2 equivalents were used and in general products were derived from epoxide ring opening.34 In a study of the structures of withanolides G,H,I,J,K, and U which were all shown to possess the 14a-hydroxy-group, it was demonstrated that the 14a-hydroxy-group influenced the epoxidation of the 5,6-double bond.35 Incorporation of ozonizable dyes as internal standards facilitated selective ozonization of... 

Withanolides.—number of new withanolides have been isolated and their structures determined (see Table of New Compounds). The conformation of the six-membered lactone ring has been established for several withanolides. Of... 

Fig. (2). General structures of withanolides with a 8-lactone or 8-lactol side chain (group A). Numbering has been added for clarity in some structures. (R, R2 = O or H,OH)...

Compounds 13-22 are structurally related to the withaphysalins, isolated from Physalis minima, which have been regarded as intermediates in the formation of the physalins. Recently Tomassini et al. published a review on withanolides isolated from the Physalis genera [21]. 

As this name had been already assigned to a structurally different withanolide (compound 1) isolated from J. bergii [12] the name trechonolide A is retained for 64. 

The first withanolide with a spiranoid y-lactone side chain, jaborosalactone P (77), was isolated from plants of Jaborosa odonelliana collected in Salta province (Argentina) [43]. Lately six structurally related compounds were found in the same plant, jaborosalactones 10 (78), 14 (79) and 15 (80) in plants collected in summer and jaborosalactones 11 (81), 12 (82), 13 (83) and 14 (79) in plants collected in autumn [44]. 

Comparison of the structure of jaborosalactone 2 (85) with that of trechonolide A (64) indicated that both compounds may have closely related biosynthetic precursors. In the former withanolide, ring closure on C-12 has occurred with a C-22 hydroxyl as shown in Fig. (4) pathway a. Oxidation of this intermediate or a related compound to the 22-ketone would allow cyclization between C-23 and the C-12 ketone to give a spiranoid withanolide (Fig. (4) pathway b). The co-occurrence of trechonolide A (64) and jaborosalactone 2 (85) in J. araucana supports this hypothesis. 

The structure of salpichrolide N (104) is particularly interesting regarding the biosynthesis of withanolides with an aromatic D ring. Whiting has proposed as a possible pathway to ring D aromatization, the oxidation of C-18 followed by a 1,2-shift of C-17 to form a new six-... 

The first studies on cancer chemopreventive activity were performed by Kennedy and co-workers on withanolides isolated from Physalis philadelphica. The most potent compounds were found to be ixocarpalactone A (34), philadelphicalactone A (36), 4p,7(3,20R-trihydroxy-l-oxowitha-2,5-dien-22,26-olide (42), and ixocarpalactone B (38), all of which contained a 4p-hydroxy-2-en-l-one structural unit [73]. 

Withanolides containing 17a-oriented side-chains are known to possess 17 -hydroxyl group which causes a strong deshielding effect on C-21 (6.1 ppm) (Structure III). The presence of a 14°-OH group is expected to shield C-12. Instead, the shift of this carbon is almost unchanged. Probably a Y-effect from the 14 Y-alcohol replaces the one from C-20. Steric hindrance from the axial oxy-substituent may have caused the rotation around where a hydrogen bond is possible (Structure IV). 

Physalins which resemble closely in their structure to withanolides occur mainly in the plants of Physalis species. The plants as such as well as the isolated physalins have been reported to exhibit varied pharmacological activity. 

Crystal structures and absolute configurations have been determined by X-ray methods for two marine sterols (8) and (9), related to gorgosterol, with a cyclopropane ring in the side-chain, for 8-aza-oestradiol, 3 -acetoxy-17a-iodoandrost-5-ene, and withanolide E, which is found to have the unusual 17a-configuration (10). Structure determinations of 2 -hydroxytestosterone... 

In addition to the plants of Solanaceae family, certain withanolides named minabeolides have been reported from the sea soft coral belonging to the genus Paraminabea, representing the first class of marine withanolides [7, 9]. Minabeolides were reported three decades ago and found to be structurally similar to the simple withanolides such as withaferin A (2). However, recently they have attracted attention because of numerious reports of their cytotoxic properties. 

---