Hanessian-Hullar reaction in the synthesis of highly substituted trans-3,4-dihydroxypyrrolidines: Rhamnulose iminosugar mimics inhibit α-glucosidase

Liu, Zilei, Yoshihara, Akihide, Jenkinson, Sarah F., Wormald, Mark R., Kelly, Ciarán, Heap, John T., Marqvorsen, Mikkel H.S., Estévez, Ramón J., Fleet, George W.J., Nakagawa, Shinpei, Izumori, Ken, Nash, Robert J. and Kato, Atsushi (2020) Hanessian-Hullar reaction in the synthesis of highly substituted trans-3,4-dihydroxypyrrolidines: Rhamnulose iminosugar mimics inhibit α-glucosidase. Tetrahedron, 76 (1). p. 130758. ISSN 0040-4020

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Official URL: https://doi.org/10.1016/j.tet.2019.130758

Abstract

The key step in the syntheses of highly substituted trans-3,4-dihydroxypyrrolidines is introduction of bromide by stereospecific and regiospecific Hanessian-Hullar reactions; benzylidene lactones of l-rhamnonolactone and 6-deoxy-l-gulonolactone allow introduction of N at C2 with inversion or retention of configuration. Initially a protecting group, the benzylidene acetal then provides a bromide at C5 to allow formation of the pyrrolidine ring. With silyl protecting groups, bromide was introduced at C5 with inversion of configuration whereas benzoyl protection gave a mixture of retention and inversion, indicative of neighbouring group participation in a Hanessian-Hullar reaction. Four stereoisomeric pyrrolidines - iminosugar mimics of α- and β-l-rhamnulose and α- and β-6-deoxy-d-sorbose were prepared. Only the α-l-rhamnulose mimic showed moderate inhibition of rhamnosidase but some were good inhibitors of α-glucosidases; none inhibited rhamnose isomerase and they had a small effect as synthetic inducers of the rhamnose catabolic operon in E. coli.

Item Type: Article
Uncontrolled Keywords: Iminosugars, Sugar mimics, Rhamnosidase inhibitors, Glucosidase inhibitors, Deoxysugars, Pyrrolidine synthesis,Benzylidene acetals, Hanessian Hullar reaction
Subjects: C700 Molecular Biology, Biophysics and Biochemistry
Department: Faculties > Health and Life Sciences > Applied Sciences
Depositing User: Ay Okpokam
Date Deposited: 21 Nov 2019 13:48
Last Modified: 03 Jan 2020 17:15
URI: http://nrl.northumbria.ac.uk/id/eprint/41565

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