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Phytochemistry. 2015 Mar;111:124-31. doi: 10.1016/j.phytochem.2014.12.011. Epub 2015 Jan 9.

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

Author information

1
Department of Hospital Pharmacy, University of Toyama, Toyama 930-0194, Japan. Electronic address: kato@med.u-toyama.ac.jp.
2
Department of Hospital Pharmacy, University of Toyama, Toyama 930-0194, Japan.
3
Institute of Biological, Environmental and Rural Sciences/Phytoquest Limited, Plas Gogerddan, Aberystwyth, Ceredigion SY23 3EB, United Kingdom.
4
Oxford Glycobiology Institute, University of Oxford, South Parks Road, Oxford OX1 3QU, United Kingdom.
5
Department of Chemistry, Wayne State University, 5101 Cass Ave, Detroit, MI 48202, United States.
6
Daniel K. Inouye College of Pharmacy, University of Hawaii at Hilo, 34 Rainbow Drive, Hilo, HI 96720, United States.
7
Oxford Glycobiology Institute, University of Oxford, South Parks Road, Oxford OX1 3QU, United Kingdom; Chemistry Research Laboratory, Department of Chemistry, University of Oxford, Mansfield Road, Oxford OX1 3TA, United Kingdom. Electronic address: george.fleet@chem.ox.ac.uk.
8
BioApply Co., Ltd., 1-95 Tsuchishimizu, Kanazawa 920-0955, Japan.

Abstract

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.

KEYWORDS:

Australine; Castanospermine; Castanospermum australe; Glycosidase inhibitor; Iminosugar; Structure–activity relationship

PMID:
25583438
DOI:
10.1016/j.phytochem.2014.12.011
[Indexed for MEDLINE]

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