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Isolation and SAR studies of bicyclic iminosugars from Castanospermum australe as glycosidase inhibitors

2015; Elsevier BV; Volume: 111; Linguagem: Inglês

10.1016/j.phytochem.2014.12.011

1873-3700

Atsushi Kato, Yuki Hirokami, Kyoko Kinami, Yutaro Tsuji, Shota Miyawaki, Isao Adachi, Jackie Hollinshead, Robert J. Nash, J. L. Kiappes, Nicole Zitzmann, Jin K., Russell J. Molyneux, George W. J. Fleet, Naoki Asano,

Enzyme Production and Characterization

We report the isolation and structural determination of fourteen iminosugars, containing five pyrrolizidines and five indolizidines, from Castanospermum australe. The structure of a new alkaloid was elucidated by spectroscopic methods as 6,8-diepi-castanospermine (13). Our side-by-side comparison between bicyclic and corresponding monocyclic iminosugars revealed that inhibition potency and spectrum against each enzyme are clearly changed by their core structures. Castanospermine (10) and 1-deoxynojirimycin (DNJ) have a common d-gluco configuration, and they showed the expected similar inhibition potency and spectrum. In sharp contrast, 6-epi-castanospermine (12) and 1-deoxymannojirimycin (manno-DNJ) both have the d-manno configuration but the α-mannosidase inhibition of 6-epi-castanospermine (12) was much better than that of manno-DNJ. 6,8-Diepi-castanospermine (13) could be regarded as a bicyclic derivative of talo-DNJ, but it showed a complete loss of α-galactosidase A inhibition. This behavior against α-galactosidase A is similar to that observed for 1-epi-australine (6) and altro-DMDP.