Modeling of acid hydrolysis of solasodine glycosides. Part I: Formation of solasodine by glycoside hydrolysis

Abstract

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...