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Kinetic models for glycoside hydrolysis and solasodiene formation are combined, P. G. CRABBE and COLIN FRYERand using previous experimental data the effect of changes in reaction conditions on hydrolysis times and the proportion of solasodiene in the final hydrolysed product are established. These are used to give a set of guidelines for commercial hydrolysis. The use of the models: for new commercial situations is explained. SCOPEMathematical models have been proposed to describe the hydrolysis of pure a-solasonine and a-solamargine (Part I), and the further reaction of pure solasodine to produce solasodiene (Part 11). The proposed models have been shown to describe adequately these three independent reactions. Methods have been presented for determination of the model parameters from experimental data. Any commercial hydrolysis will be more complex, involving all of these three reactions. The individual kinetic models need to be combined to describe such systems. The description of the hydrolysis reaction must be extended to incorporate solasodiene formation from the released solasodine so that the time for hydrolysis and the proportion of solasodiene in the final product can be predicted. Consideration of the predictions of this combined model, using parameter values obtained in the studies of the individual reactions, should provide guidance on the optimization of the hydrolysis process. CONCLUSIONS AND SIGNIFICANCEPrevious models are easily extended to more complex hydrolysis situations; a model is established for the most general hydrolysis system, that of the hydrolysis of a mixed glycoside substrate with allowance for solasodiene formation from the released solasodine. Using the experimental rate data for a-solasonine hydrolysis (from Part I) and that for the solasodine to solasodiene conversion (from Part II), estimates of the reaction times (for specified conversions) and of solasodiene percentages in the final product have been obtained. For the conditions studied, solasodiene percentages in the final product are low (generally less than 1Y0k the problem of solasodiene formation is not as great as previously reported, provided that the reaction is stopped once hydrolysis is complete. Reaction rates increase with acid concentration and temperature, but decrease sharply with the addition of water to an alcohol solvent. The glycoside concentration has no effect unless solubility limits of the intermediates are exceeded. = initial concentration LITERATURE CITED Crabbe, P. G., and C. Fryer, "Rapid quantitative analysis of solasodine, solasodine glycosides and solasodiene by high pressure liquid chromatography," J . Chromtogr., 187, p. 87 (1980). Tourky, A. R., A. A. Abdel-Hamid, and I. Z. Slim, "Acidity in mixed solvents: 11. Hammett's acidity function in isopropanol-and ethylene glycol-water mixtures,

Solasodine from Solanurn plants is a potential raw material for steroid drug manufacture. Acid hydrolysis of the naturally occuring glycosides of solasodine is a major step in production of the aglycone. As part of a detailed study of the hydrolysis of solasodine glycosides, the hydrolysis procedure has been mathematically modelled. Two models are presented and have been used to obtain kinetic data for ~e reactions at a number of different reaction conditions. The subsequent conversion of solasodine to solasodiene is considered in Part I1 of this paper; the combined reactions and guidelines for commercial hydrolysis are presented in Part 111. P. G. CRABBE and COLIN FRYERDepartment of Chemical Engineering Monash University Clayton, Vlctorla, Australia SCOPEIn the plants Solanurn avicuIare and Solanurn laciniaturn, solasodine is the only steroidal alkaloid present. This makes these two plants, both natives to Australia and New Zealand, attractive commercial sources of raw steroid. In these plants solasodine occurs as the triglycosides solasonine and solamargine, which must be hydrolyzed to release the solasodine. During hydrolysis, diglycosides and monoglycosides are formed as intermediates. The solasodine product may undergo further reaction to solasodiene, an impurity which is difficult to remove.No direct evaluation of reaction rates for hydrolysis of solasodine glycosides has been reported previously, and only a rough idea of the hydrolysis times necessary under various reaction conditions has been established. Many of the presented results and conclusions regarding the effects of changing the reaction conditions are of doubtful validity.To minimize the time for hydrolysis, while at the same time restricting the amount of solasodiene formed to an acceptable limit, one must be able to predict accurately the end point of the hydrolysis. For this purpose it is necessary to know the rate constants for the various reactions involved. It is not sufficient to determine only an overall rate for the conversion of triglycoside to aglycone. The process will not be adequately described by an overall rate equation. In addition, the glycosidic mixture presented for hydrolysis may already be partially hydrolyzed by natural processes. If a kinetic model involving the conversions among the glycosides, the partial glycosides and the aglycone is developed and individual rate constants determined, the starting material can be analyzed and the hydrolysis time to reach a particular conversion accurately predicted. CONCLUSIONS AND SIGNIFICANCEBecause the hydrolysis of solasodine glycosides is carried out under strongly acidic conditions, reaction rates are not first order with respect to aid concentration, but can be described in terms of acidity functions. The consumption of acid which occurs in acidified aqueous alcohol solvents can be neglected in glycoside hydrolysis studies only if hydrochloric acid and isopropanol are used.Hydrolysis of each of the two1 glycosides solasonine and solamargine proceeds independently and may be tre...

Solasodine from Solanum plants is a potential raw material for steroid drug manufacture. Acid hydrolysis of the naturally occurring glycosides of solasodine is a major step in production of the aglycone. In this study, high pressure liquid chromatography is being used to follow the sequence of sugar cleavage reactions during hydrolysis. A kinetic model has been developed to describe the hydrolysis reactions.