12-Oxygenated withanolides

Recently, Ahmad et al. isolated two 14-oxygenated withanolides, compounds 9 and 10 from plants of Physalis peruviana collected from District Chitral, Pakistan and a new withanolide glycoside (compound 11) which presented a 14,20-epoxy functionality [15,16]. Dinan et al. had previously reported the isolation of 28-hydroxywithanolide E (12) from calices of this plant [17]. 

The cytotoxic behavior of the withanolides, having 7 S or 16a acetoxy group, was evaluated by Minguzzi in 2002. They observed that above-mentioned functionalities have no contributions in the cytotoxicity of the withanolides [78]. However, the C-17-oxygenated withanolides with C-16a hydroxyl or acetoxy group showed enhanced the cytotoxicity [79]. 

P. chenopodifolia Physachenolides A - E (18-oxygenated withanolide E-type metabolites) Maldonado et al. (2004)... 

The steroidal 4/3-acetoxy-5/J,6/l/-epoxy-2-en-l-one system 546 was converted at room temperature into the 6/3-hydroxy-2,4-dien-l-one 547 by reductive elimination of the vicinal oxygen function, and the reaction has been applied to the synthesis of withanolide[352]. 

The presence of an oxygenated function at C-23 allows the formation of a y-lactone side chain (group B), these withanolides may be divided in five subgroups, spiranoid withanolides, trechonolides, subtriflora-y-lactones, ixocarpalactones and perulactones, Fig. (3)... 

A 16,18,20-trioxygenated withanolide, 13p-hydroxymethyl-subtrifloralactone E (43) was isolated from plants of Deprea subtriflora (Riz Pavon) D Arcy collected in Peru together with a series of highly oxygenated C-18 norwithanolides, subtrifloralactones A-L (44-55). Compounds A, B, C, K and L (44, 45, 46, 54, 55) incorporate a hemiketal bridge like that found in the trechonolide group, while subtrifloralactones H, I and J (51-53) presented a new type of hemiketal bridge between C-20 and C-12 [30,31]. 

In addition to the oxidative processes at the above three centres, one of the characteristic features of the plants producing withanolides is their extraordinary ability to introduce oxygen functions at almost every position of the carbocyclic skeleton and side chain. Till now, there are only one secondary (C-11) and two tertiary (C-8 and C-9) carbon atoms which have not been found to be oxidised. 

Almost all types of oxygen functionalities are present in this class of steroidal lactones, and the characteristic IR spectral bands for various functionalities appear in the spectra. The characteristic enone and a,) -unsaturated Mactone moieties of withanohdes show absorptions at or near the 1,660 and 1,710 cm, respectively. An IR absorption at 1,778 cm is due to carbonyl stretching vibrations in five-membered lactone ring, found in all physalins and other classes of withanolides with modified skeleton [34-36]. 

The mass spectra of other types of withanolides exhibit no systemic fragmentation pattern, which may be due to their highly complex and oxygenated skeletons. 

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