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

Journal article

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.

Authors: Liu, Z; Yoshihara, A; Jenkinson, SF; Wormald, MR; Kelly, C

• Publication status: Published
• Peer review status: Peer reviewed
• Publisher: Elsevier
• Journal: Tetrahedron
• Volume: 76
• Issue: 1
• Article number: 130758
• Publication date: 2019-11-06
• Acceptance date: 2019-10-31
• DOI: 10.1016/j.tet.2019.130758
• ISSN: 0040-4020
• Language: English
• Keywords: iminosugars; rhamnosidase inhibitors; sugar mimics; glucosidase inhibitors; deoxysugars; FFR; Hanessian Hullar reaction; benzylidene acetals; pyrrolidine synthesis