Neuroprotective glucosides of magnolol and honokiol from microbial-specific glycosylation

Thirteen new glucosides (1-13) of magnolol and honokiol were obtained from specific O-glycosylation by two filamentous fungi, Cunninghamella echinulata AS 3.3400 and Rhizopus japonicus ZW-4. The glucosides' structures were determined on the basis of extensive spectroscopic (HRESIMS, 1D and 2D NMR, and CD) analyses and a chemical method. C echinulata appeared to transfer a glucosyl moiety to 2-OH of magnolol and honokiol, whereas R. japonicus preferred to regio-specifically transfer a glucosyl moiety to 4'-OH when honokiol was as the substrate. In addition, hydroxylation by C echinulata and specific 6-O-acylation of the introduced glucosyl moiety by R. japonicus were observed as minor reactions. Bioassay results indicated that glucosides 1-12 together with magnolol and honokiol at 10 mu M attenuated the glutamate-induced toxicity in SK-N-SH cells to levels comparable to the results for MK-801, a positive control. However, the water-solubility of major glucosylated products (1, 8, and 11) increased greatly. (C) 2014 Elsevier Ltd. All rights reserved.