The first conduritol aziridine (1,2-dideoxy-1,2-epimino-myo-inositol, 1) was synthesized in seven steps from myo-inositol (2) and inhibits pABG5 β-glucosidase and yeast ⍺-glucosidase irreversibly. 1,2-0-Cyclohexylidene-myo-inositol (3) was obtained by reaction of 2 with cyclohexanone. Benzylation of 3 followed by hydrolysis of the ketal gave l,4,5,6-tetra-0-benzyl-myo-inositol (5). The two free hydroxyl groups in 5 were methanesulfonylated and the axial mesyl group in l,4,5,6-tetra-0-benzyl-2,3-di-0-methanesulfonyl-myo-inositol (12) was selectively displaced by an azido group. The resulting 1-azido-2,3,4,5-tetxa-0-benzyl-1-deoxy-6-0-methanesulfonyl-scyllo-inositol (13) was hydrogenated in the presence of HC1 to give 1-amino-1-deoxy-2-0-methanesulfonyl-scyllo-inositol (24) hydrochloride. Cyclisation of 24 under basic aqueous conditions yielded
DL-1. [Formula Omitted] The dissociation constant Ki and the inactivation rate constant ki for inactivation of pABG5 β-glucosidase by 1 were calculated to be 3.0 mM and 0.077 min⁻¹ respectively. For yeast ⍺-glucosidase inactivation, values of Ki, and ki were found to be 9.5 mM and 0.39 min-1 respectively. Finally, 24 and 31 were tested as reversible (non-covalent) inhibitors of both the glucosidases and the respective inhibition constants (Ki) determined. / Science, Faculty of / Chemistry, Department of / Graduate
| Identifer | oai:union.ndltd.org:UBC/oai:circle.library.ubc.ca:2429/27852 |
| Date | January 1988 |
| Creators | Caron, Gaétan |
| Publisher | University of British Columbia |
| Source Sets | University of British Columbia |
| Language | English |
| Detected Language | English |
| Type | Text, Thesis/Dissertation |
| Rights | For non-commercial purposes only, such as research, private study and education. Additional conditions apply, see Terms of Use https://open.library.ubc.ca/terms_of_use. |
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