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 μM 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.