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

Zilei Liu, Akihide Yoshihara, Sarah Jenkinson, Mark Wormald, Ciarán Kelly, John T Heap, Mikkel Marqvorsen, Ramón Estévez, George Fleet, Shinpei Nakagawa, Ken Izumori, Robert Nash, Atsushi Kato

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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-this should be small unnpercase D not L why can I not correct this-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.

Original languageEnglish
Article number130758
JournalTetrahedron
Volume76
Issue number1
Early online date6 Nov 2019
DOIs
Publication statusPublished - 3 Jan 2020

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