Starting from levoglucosan and mannosan, we prepared a series of O-benzylated phenyl 2-azido-2,3-dideoxy-3-fluoro- and phenyl 2-azido-2,4-dideoxy-4-fluoro-1-thio-D-hexopyranosides of gluco and galacto configuration 1–4 . The key intermediates were C-3 and C-4 deoxofluorinated 1,6-anhydro-2-azido-2-deoxyhexopyranoses . Reaction with PhSTMS/ZnI₂ effected cleavage of 1,6-anhydro bridge , and subsequent O-benzylation gave the target glycosyl donors 1–4 . Low-temperature NMR revealed that treatment of 1 with Tf₂O/Ph₂SO in DCM at –78 °C led to the formation of anomeric α-triflate 5 and both anomers of the oxosulfonium triflate α-6 and β-6 .
The anomeric stereoselectivity in glycosylation with 1–4 was investigated using the preactivation-based glycosylation protocol with the Tf₂O/Ph₂SO promoter system , and a series of model carbohydrate acceptors of varying reactivity. Glycosylation of reactive acceptors (primary alcohols, unhindered secondary equatorial alcohols) favored formation of β-glycosides. β-Selectivity gradually eroded with decreasing acceptor reactivity, and glycosylation of the least reactive acceptors was almost unselective for gluco-configured donors (1) and (2). On the other hand, galacto-configured donors (3) and (4) showed reversal to moderate to good α-selectivity with unreactive acceptors .
Financial Support of the Czech Science Foundation is gratefully acknowledged (Project GA 17-18203S)
- Kurfiřt, M.; Červenková Šťastná, L.; Dračínský, M.; Müllerová, M.; Hamala, V.; Cuřínová, P.; Karban, J. Stereoselectivity in Glycosylation with Deoxofluorinated Glucosazide and Galactosazide Thiodonors. J. Org. Chem. 2019, DOI: 10.1021/acs.joc.9b00705.
- Horník, Š.; Červenková Šťastná, L.; Cuřínová, P.; Sýkora, J.; Káňová, K.; Hrstka, R.; Císařová, I.; Dračínský, M.; Karban, J. Synthesis and in vitro cytotoxicity of acetylated 3-fluoro, 4-fluoro and 3,4-difluoro analogs of D-glucosamine and D-galactosamine. Beilstein J. Org. Chem. 2016, 12, 750-759.
- Wang, L.-X.; Sakairi, N.; Kuzuhara, H. 1,6-Anhydro-β-D-glucopyranose derivatives as glycosyl donors for thioglycosidation reactions. J. Chem. Soc., Perkin Trans. 1 1990, 1677-1682.
- Codée, J. D. C.; Litjens, R. E. J. N.; den Heeten, R.; Overkleeft, H. S.; van Boom, J. H.; van der Marel, G. A. Ph₂SO/Tf₂O: a Powerful Promotor System in Chemoselective Glycosylations Using Thioglycosides. Org. Lett. 2003, 5, 1519-1522.