Spirosolane alkaloids

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. 

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. 

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... 

Spirosolanes The spirosolane alkaloids can be divided into two series that differ in their stereochemistry at C-22 and C-25 [(22/f,25f )-series as in solasodine and the (22S,255)-series as in tomatidenol]. For 3/S-aminospi-rosolanes and N-hydroxysolasodine, see Lit. formula, see figure 2. 

Steroidal alkaloids of the Solanaceae can therefore be divided into two categories based on the aglycone the solanidine- and the solasodine-type alkaloids. The basic skeleton of the former alkaloids is known as solanidane, and that of the latter alkaloids is known as a spirosolane skeleton. 

Epiminocholestanes. Alkaloids with this structure are intermediates in the biosynthesis of spirosolane, so-lanidine, a-epiminocyclohemiacetal, and 3-aminospirostane alkaloids. (25R)-26-Aminocholesterol (68) is precursor to the 22,26-epiminocholestanes. The biosynthesis of verazine (47), etioline (66), and solacongestidine (65) is discussed above. 

Particularly because of the potential importance of the spirosolane alkaloids as starting materials for the industrial production of hormonal steroids, a munber of modified irosolanes have been synthesized. The d radation of these products (see Swtion IV,C) should lead to modified pregnanes. 

The biosynthesis of spirosolane alkaloids in tissue cultures of Solanum spedes has been reported 317-320, 375-377, cf. 321-325). Still, other authors were able to find only diosgenin and not any solasodine (1) in tissue cultures of S. laciniatum 326 cf. 316). The presence and content of spirostanols and/or spirosolanols may be dq)endent on the ratio of plant growth substances, e.g., 2,4-D, kinetin, and gibberellic add 318). It is reported that the addition of cholesterol increases the solasodine content 320). 

Hydroxy-spirosolanes (Fig. 7.19). Solasodine is the dominating congener of the 25/ -series (22ot/V-configurated) and even the most frequent individual aglycone of all types of solanaceous glycoalkaloids. It was detected unequivocally in 207 out of 367 steroidal alkaloid-positive Solanum spp. (56%). 

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