Divergent synthesis of new α-glucosidase inhibitors obtained through a vinyl Grignard-mediated carbocyclisation

Literature Information

Publication Date 2018-08-07
DOI 10.1039/C8OB01433G
Impact Factor 3.876
Authors

Ida M. B. Knudsen, Christinne Hedberg, Daisuke Ide, Anne Brinkø, Espen Z. Eikeland, Atsushi Kato, Henrik H. Jensen


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Abstract

Four new α-glucosidase inhibitors have been synthesised through 5–8 synthetic steps from a common synthetic intermediate obtained through a recently developed carbocyclisation. The compounds were designed as hybrids of the known glucosidase inhibitors valienamine, voglibose and miglitol. All four compounds showed activity against rat intestinal sucrase with the most potent inhibitor acting at low micromolar concentration. The newly synthesised compounds were not as potent as miglitol against sucrase but showed greater selectivity towards the tested glycosidases. The most potent inhibitors were docked into a homology model built for this study of rat intestinal sucrase explaining the difference in potency between two diastereoisomers with varying orientation of a secondary amine.

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Organic & Biomolecular Chemistry

Organic & Biomolecular Chemistry
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Organic & Biomolecular Chemistry (OBC) publishes original and high impact research and reviews in organic chemistry. We welcome research that shows new or significantly improved protocols or methodologies in total synthesis, synthetic methodology or physical and theoretical organic chemistry as well as research that shows a significant advance in the organic chemistry or molecular design aspects of chemical biology, catalysis, supramolecular and macromolecular chemistry, theoretical chemistry, mechanism-oriented physical organic chemistry, medicinal chemistry or natural products. Articles published in the journal should report new work which makes a highly-significant impact in the field. Routine and incremental work is generally not suitable for publication in the journal. More details about key areas of our scope are below. In all cases authors should include in their article clear rationale for why their research has been carried out.

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