Synthesis and Glycosidation of Anomeric Halides: Evolution from Early Studies to Modern Methods of the 21st Century

Abstract

Advances in synthetic carbohydrate chemistry have dramatically improved access to common glycans. However, many novel methods still fail to adequately address challenges associated with chemical glycosylation and glycan synthesis. Since a challenge of glycosylation has remained, scientists have been frequently returning to the traditional glycosyl donors. This review is dedicated to glycosyl halides that have played crucial roles in shaping the field of glycosciences and continue to pave the way toward our understanding of chemical glycosylation.

An Improved Protocol for the Stereoselective Synthesis of β-d-Glycosyl Fluorides from 2-O-Acyl Thioglycosides

“…When 1 was reacted with 0.2 equiv of NBS, excess XtalFluor-M, and Et 3 N• 3HF (entry 4), further improvements were seen to both the yield (95%) and 1,2-trans stereoselectivity (90:10 2a:2b). No trace of 3 was detected in the 1 H NMR spectrum of the crude product mixture. Finally, we note that substituting substoichiometric NBS with N-iodosuccinimide (NIS) for the reaction of 1 failed to produce a successful reaction (entry 5).…”

“…R f (4:1 n-hexane/EtOAc) = 0.24 (8a) and 0.20 (8b). Data for 8a (β-anomer): 1 H NMR (500 MHz, CDCl 3 ) δ 5.31 (dd, 1H, J 1,F = 52.0 Hz, J 1,2 = 6.1 Hz, H-1), 5.25−5.17 (m, 2H, H-3, H-4), 5.10 (m, 1H, H-2), 4.26 (dd, 1H, part A of ABX, J 5,6a = 2.7 Hz, H-6a), 4.21 (dd, 1H, part B of ABX, J 6a,6b = 12.1 Hz, J 5,6b = 2.9 Hz, H-6b), 3.93−3.87 (m, 1H, H-5), 2.11 (s, 3H, -CH 3 ), 2.10 (s, 3H, -CH 3 ), 2.04 (s, 3H, -CH 3 ), 2.03 (s, 3H, -CH 3 ); 13 C{ 1 H} NMR (125 MHz, CDCl 3 ) δ 170.8, 170.7, 170.3, 170.1 (4 × C�O), 106.3 (d, J 1,F = 219.2 Hz, C-1), 72.1 (d, J 5,F = 3.9 Hz, C-5), 71.8 (d, J 3,F = 8.3 Hz, C-3), 71.2 (d, J 2,F = 28.8 Hz, C-2), 67.5 (C-4), 62.2 (C-6), 20.8(6), 20.8(1), 20.7(3), 20.7(1); 19 F NMR (470 MHz, CDCl 3 ) δ −137.1 (dd, J 1,F = 52.0 Hz, J 2,F = 10.4 Hz); LRMS (ESI) m/z 373.2 [M + Na] + (C 14 H 19 FNaO 9 ). All NMR data were in agreement with the literature.…”

“…All NMR data were in agreement with the literature. 4b Key data for 8b (α-anomer): 1 H NMR (500 MHz, CDCl 3 ) δ 5.75 (dd, 1H, J 1,F = 52.8 Hz, J 1,2 = 2.8 Hz, H-1), 4.98 (m, 1H, H-2); 19 F NMR (470 MHz, CDCl 3 ) δ −149.7 (dd, J 1,F = 52.9 Hz, J 2,F = 24.2 Hz).…”

“…Sufficient quantities of each anomer were obtained to enable individual characterization. Data for 12a (β-anomer): 1 ). All NMR data were in agreement with the literature.…”

“…Glycosyl fluorides represent a family of robust glycosyl donors 1,2 and valuable substrates or probes for enzyme assays and chemical biological studies. 3 As benefits of their high chemical and thermal stability, they can be chromatographed on silica without decomposing and display relatively inert behavior toward a broad range of donor activation protocols.…”