Stereo- and regioselective hydroboration of 1- exo-methylene pyranoses: discovery of aryltriazolylmethyl C-galactopyranosides as selective galectin-1 inhibitors

Alexander Dahlqvist; Axel Furevi; Niklas Warlin; Hakon Leffler; Ulf J Nilsson

doi:10.3762/bjoc.15.102

Stereo- and regioselective hydroboration of 1- exo-methylene pyranoses: discovery of aryltriazolylmethyl C-galactopyranosides as selective galectin-1 inhibitors

Beilstein J Org Chem. 2019 May 7:15:1046-1060. doi: 10.3762/bjoc.15.102. eCollection 2019.

Authors

Alexander Dahlqvist¹, Axel Furevi^#¹, Niklas Warlin^#¹, Hakon Leffler², Ulf J Nilsson¹

Affiliations

¹ Centre for Analysis and Synthesis, Department of Chemistry, Lund University, Box 124, SE-221 00 LUND, Sweden.
² Division of Microbiology, Immunology and Glycobiology, Lund University, BMC C12, SE-221 84 LUND, Sweden.

^# Contributed equally.

Abstract

Galectins are carbohydrate recognition proteins that bind carbohydrates containing galactose and are involved in cell signaling and cellular interactions, involving them in several diseases. We present the synthesis of (aryltriazolyl)methyl galactopyranoside galectin inhibitors using a highly diastereoselective hydroboration of C1-exo-methylene pyranosides giving inhibitors with fourfold or better selectivity for galectin-1 over galectin-3, -4C (C-terminal CRD), -4N (N-terminal CRD), -7, -8C, -8N, -9C, and -9N and dissociation constants down to 170 µM.

Keywords: C-galactoside; galectin-1; hydroboration; inhibition; selective; triazole.