Microbial Transformation Of Stevioside Derivants

In recent years, more and more pharmacological activity of stevioside and its derivatives have gradually been known in the fields of diabete mellitus, cardiovascular and the development of Natural drugs, such as hypoglycemic, antihypertensive action, inhibiting cancer cell proliferation and so on. Thus, As for isosteviol which is the acid hydrolysis product of stevioside, it must have good prospect to pick it as the lead compound which can be modifyed the structure properly, may be promoted binding with its receptor or targets, enhanced the existing properties, and finally help developing new medicaments.Biotransformation is ever such a useful tool in Structural modification of natural product-based drug discovery. Inert carbon in a series of compounds could be catalyzed with the hydroxyl by the regioselective and stereo-selectivity synthesis of the technique. As for some complex organic reactions, it may be extremely specific and quickly completed by using biotransformation.In this article, the way which combine Chemical synthesis and biotransformation was be used to modify the structure of isosteviol by introducing the hydroxyl. The main resuts were as following:Cunninghamella echinulata had been selected as transforming bacteria form eleven test epiphytes and been used for a large scale liquid fermentation. Incubation of substrate ent-16β-hydroxybeyeran-19-oic acid with Cunninghamella echinulata yielded seven major metabolites, five of which were identified by a series of spectral techniques (UV, IR, HR-ESI-MS, ¹H-NMR, ¹³C-NMR, HSQC, HMBC, NOESY, et al.) as ent-9α,16β- dihydroxybeyeran-19-oic(JY-1), ent-12α,16β-dihydroxybeyeran-19-oic(JY-4), ent-14β,16β- dihydroxybeyeran-19-oic acid(JY-5), ent-7β,16β-dihydroxybeyeran-19-oic acid(JY-6), ent- 16β-hydroxybeyeran-19-α-D-glucopyranosyl ester(JY-7). In the five identified products, two were proved as JY-5 and JY-7 by NMR spectral comparison with literature data. And JY-1, JY-4 and JY-6 are novel compounds, and the stereostructure of JY-1 had been confirmed by X-ray crystallography. Actually, spectral data of JY-5 were also little reported in the literature.