Spirosolane

Steroid alkaloids have been isolated from four famihes of terrestrial plant sources (Soianaceae l iliaceae pOijnaceae and Buxaceae) two animal sources (Saiamandra and Phjllobates) and several marine sources. Steroid alkaloids can be classified based on stmcture and fall into a variety of categories. The spirosolanes contain a cholestane skeleton with a C20 spiroaminoketal moiety, as exemplified by the most abundant members of this class, veramine... 

The structural features of the solanum alkaloids are based on two primary skeletal configurations solanidane, with or without glycoside functionalities, as featured by the toxic and teratogenic steroidal alkaloids a-chaconine and a-solanine with the indolizidine type E-F ring (Figure 2.7a) and the spirosolane... 

Cyclopamine also interferes with cholesterol metabolism that results in decreased cholesterol synthesis and the accumulation of late biosynthetic intermediates. Cyclopamine was evaluated as an inhibitor of multi-drug resistance in tumor cells. Intrinsic or acquired resistance of tumor cells to cytotoxic drugs is a major cause of failure of chemotherapy. Both cyclopamine and the spirosolane alkaloid tomatidine from tomatoes act as potent and elfective chemosensitizers in multidrug-resistant cells (Lavie et ah, 2001). Therefore, plant steroidal alkaloids, such as cyclopamine and tomatidine, or their analogs, may serve as chemosensitizers in combination with chemotherapy and conventional cytotoxic drugs for treating multidrug-resistant cancers. 

Figure 14.3 Potato glycoalkaloids. (a) is tomatine, a spirosolane and (b) solanine, a solanidane.

Potato GAs usually belong to one of two structural types, either solanidanes or spirosolanes (Figure 14.3). Solanine and chaconine, both solanidanes, often comprise upwards of 90% of the total GA complement of domesticated potatoes, with chaconine often more abundant than solanine (Griffiths et al., 1997 Sotelo and Serrano, 2000). 

Solasodine (16a) is an important starting material for the preparation of 3/ -acetoxypregna-5,16-dien-20-one (17).18 Hydrogenation of the latter over Raney nickel gave the epimeric pregnenols (18a), which were converted (by standard reactions) into the amines (18b) and into the dimethylamino-pregnanes (19a) and (19b).17 The 3/ -amino-spirosolanes (20a), (20b), and (20c) have been prepared... 

Bulbs of F. camtschatcensis yielded solanidine (36a) together with traces of hapepunine (34a), veralkamine, an unidentified dihydroxy-spirosolane, and a new aglycon, i.e. camtschatcanidine (36b).54 The structure assigned to camtschat-canidine was deduced from the spectroscopic data, and in particular by comparison of its 13C n.m.r. spectrum with that of solanidine. The structure and stereochemistry proposed were proven by the reduction (by LiAlH4) of the O-acetyl-O-tosyl derivative (36c) of camtschatcanidine to yield solanidine. 

Solasodlns (spirosolane-type) Solanidine (solanidane-type)... 

Steroidal Alkaloids. Photolysis of (22S 25S)-N-chloro-22,26-imino-5os-cholestan-3P-ol and the corresponding l6p-hydroxy substituted (22S 25R)-> (22S 25S)-, and (22-S 23R)-N-chloro compounds caused fragmentation to a mixture of the corresponding 20R and 20S chloropregnane derivatives. Whereas photolysis of (22R 25S)-N-chloro-22,26-imino-50-cholestan-5P-ol gave the corresponding Ib-chloro derivative. " UV-irradiation of the stereoisomeric N-nitroso-22,26-iminocholestane-3P,l6p-diols in acidic solution led to the corresponding spirosolane alkaloids soladulcidine,. solasodine, and tomatidine respectively, by way of the intermediate... 

As a result of the chromic acid oxidation the location of the second hydroxyl function in etioline appeared to be at C-16. The oxo product of 102 showed the absorption of a five- and a six-membered ring ketone in its IR spectrum. Compound 102 failed to cyclize to the spirosolane and therefore the a-orientation was assigned to the hydroxyl function at C-16. Biogenetic consideration indicated the 25S configuration for etioline. The structure 102, (25S)-22,26-epiminocholesta-5,22(i T)-diene-3jS,16a-diol, was proposed for the alkaloid. 

It was reported earlier that 16g-hydroxy-22,26-epiminocholestane derivatives such as solaverbascine (16) were oxidised smoothly by manganese dioxide to yield spirosolane derivatives such as sola-... 

Appendix) is graphically emphasized in Fig. (11) with values of the relative teratogenic potency of individual steroidal alkaloids from Table 2 placed adjacent to their structural type. The variance in values for the jervanes, solanidanes, and spirosolanes primarily reflects the level of saturation at C-5, C-6 e.g., 100 vs. 40 for jervanes, 32 vs. 9 for solanidanes, and 6 vs. 4 for spirosolanes. In each instance the higher value... 

Table 3. The Embryolethality and Teratogenicity of Jervanes, Spirosolanes, and Solanidanes... 

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