Multiple fluorination of glycostructures has emerged as an attractive way of modulating their protein affinity, metabolic stability, and lipophilicity. Here we described the synthesis of a series of mono-, di- and trifluorinated N-acetyl-ᴅ-glucosamine and ᴅ-galactosamine analogs. The key intermediates are the corresponding multiply fluorinated glucosazide and galactosazide thioglycosides prepared from deoxyfluorinated 1,6-anhydro-2-azido-β-ᴅ-hexopyranose precursors by ring-opening reaction with phenyl trimethylsilyl sulfide. Nucleophilic deoxyfluorination at C4 and C6 by reaction with DAST, thioglycoside hydrolysis and azide/acetamide transformation completed the synthesis.

Department of Bioorganic Compounds and Nanocomposites Institute of Chemical Process Fundamentals of the CAS v v i Rozvojová 135 16502 Praha 6 Czech Republic

NMR Spectroscopy group Institute of Organic Chemistry and Biochemistry of the CAS Flemingovo náměstí 542 2 16000 Praha Czech Republic

University of Chemistry and Technology Prague Technická 5 16628 Praha 6 Czech Republic

Zobrazit více v PubMed

Linclau B, Ardá A, Reichardt N-C, Sollogoub M, Unione L, Vincent S P, Jiménez-Barbero J. Chem Soc Rev. 2020;49(12):3863–3888. doi: 10.1039/c9cs00099b. PubMed DOI

Williams S J, Withers S G. Carbohydr Res. 2000;327:27–46. doi: 10.1016/s0008-6215(00)00041-0. PubMed DOI

Namchuk M, Braun C, McCarter J D, Withers S G. Fluorinated sugars as probes of glycosidase mechanisms. In: Ojima I, Ojima J R, Welch J T, editors. Biomedical Frontiers of Fluorine Chemistry. Vol. 639. Washington, DC, USA: American Chemical Society; 1996. pp. 279–293. ((ACS Symposium Series)). DOI

Williams D A, Pradhan K, Paul A, Olin I R, Tuck O T, Moulton K D, Kulkarni S S, Dube D H. Chem Sci. 2020;11:1761–1774. doi: 10.1039/c9sc05955e. PubMed DOI PMC

Glaudemans C P J, Kováč P, Nashed E M. Methods Enzymol. 1994;247:305–322. doi: 10.1016/s0076-6879(94)47023-5. PubMed DOI

Valverde P, Quintana J I, Santos J I, Ardá A, Jiménez-Barbero J. ACS Omega. 2019;4:13618–13630. doi: 10.1021/acsomega.9b01901. PubMed DOI PMC

Gimeno A, Valverde P, Ardá A, Jiménez-Barbero J. Curr Opin Struct Biol. 2020;62:22–30. doi: 10.1016/j.sbi.2019.11.004. PubMed DOI PMC

Biffinger J C, Kim H W, DiMagno S G. ChemBioChem. 2004;5:622–627. doi: 10.1002/cbic.200300910. PubMed DOI

van Straaten K E, Kuttiyatveetil J R A, Sevrain C M, Villaume S A, Jiménez-Barbero J, Linclau B, Vincent S P, Sanders D A R. J Am Chem Soc. 2015;137:1230–1244. doi: 10.1021/ja511204p. PubMed DOI

Dohi H, Périon R, Durka M, Bosco M, Roué Y, Moreau F, Grizot S, Ducruix A, Escaich S, Vincent S P. Chem – Eur J. 2008;14:9530–9539. doi: 10.1002/chem.200801279. PubMed DOI

Thanna S, Lindenberger J J, Gaitonde V V, Ronning D R, Sucheck S J. Org Biomol Chem. 2015;13:7542–7550. doi: 10.1039/c5ob00867k. PubMed DOI PMC

Vermersch P S, Tesmer J J G, Quiocho F A. J Mol Biol. 1992;226:923–929. doi: 10.1016/0022-2836(92)91041-m. PubMed DOI

Denavit V, Lainé D, St-Gelais J, Johnson P A, Giguère D. Nat Commun. 2018;9:4721. doi: 10.1038/s41467-018-06901-y. PubMed DOI PMC

St-Gelais J, Bouchard M, Denavit V, Giguère D. J Org Chem. 2019;84:8509–8522. doi: 10.1021/acs.joc.9b00795. PubMed DOI

St‐Gelais J, Côté É, Lainé D, Johnson P A, Giguère D. Chem – Eur J. 2020;26(59):13499–13506. doi: 10.1002/chem.202002825. PubMed DOI

Linclau B, Wang Z, Compain G, Paumelle V, Fontenelle C Q, Wells N, Weymouth-Wilson A. Angew Chem, Int Ed. 2016;55:674–678. doi: 10.1002/anie.201509460. PubMed DOI PMC

Johannes M, Reindl M, Gerlitzki B, Schmitt E, Hoffmann-Röder A. Beilstein J Org Chem. 2015;11:155–161. doi: 10.3762/bjoc.11.15. PubMed DOI PMC

Sun X-L, Kanie Y, Guo C-T, Kanie O, Suzuki Y, Wong C-H. Eur J Org Chem. 2000:2643–2653. doi: 10.1002/1099-0690(200007)2000:14<2643::aid-ejoc2643>3.0.co;2-1. DOI

Axer A, Jumde R P, Adam S, Faust A, Schäfers M, Fobker M, Koehnke J, Hirsch A K H, Gilmour R. Chem Sci. 2021;12:1286–1294. doi: 10.1039/d0sc04297h. PubMed DOI PMC

Malassis J, Vendeville J-B, Nguyen Q-H, Boujon M, Gaignard-Gaillard Q, Light M, Linclau B. Org Biomol Chem. 2019;17:5331–5340. doi: 10.1039/c9ob00707e. PubMed DOI

Bresciani S, Lebl T, Slawin A M Z, O'Hagan D. Chem Commun. 2010;46:5434–5436. doi: 10.1039/c0cc01128b. PubMed DOI

Sharma M, Bernacki R J, Paul B, Korytnyk W. Carbohydr Res. 1990;198:205–221. doi: 10.1016/0008-6215(90)84293-4. PubMed DOI

Werz D B, Ranzinger R, Herget S, Adibekian A, von der Lieth C-W, Seeberger P H. ACS Chem Biol. 2007;2:685–691. doi: 10.1021/cb700178s. PubMed DOI

Fu C, Zhao H, Wang Y, Cai H, Xiao Y, Zeng Y, Chen H. HLA. 2016;88:275–286. doi: 10.1111/tan.12900. PubMed DOI

Berkin A, Szarek W A, Kisilevsky R. Carbohydr Res. 2000;326:250–263. doi: 10.1016/s0008-6215(00)00049-5. PubMed DOI

Horník Š, Červenková Šťastná L, Cuřínová P, Sýkora J, Káňová K, Hrstka R, Císařová I, Dračínský M, Karban J. Beilstein J Org Chem. 2016;12:750–759. doi: 10.3762/bjoc.12.75. PubMed DOI PMC

Morrison Z A, Nitz M. Carbohydr Res. 2020;495:108071. doi: 10.1016/j.carres.2020.108071. PubMed DOI

Hough L, Penglis A A E, Richardson A C. Can J Chem. 1981;59:396–405. doi: 10.1139/v81-061. DOI

Sharma M, Bernacki R J, Hillman M J, Korytnyk W. Carbohydr Res. 1993;240:85–93. doi: 10.1016/0008-6215(93)84174-5. PubMed DOI

Wasonga G, Tatara Y, Kakizaki I, Huang X. J Carbohydr Chem. 2013;32:392–409. doi: 10.1080/07328303.2013.815196. PubMed DOI PMC

Wagner S, Mersch C, Hoffmann-Röder A. Chem – Eur J. 2010;16:7319–7330. doi: 10.1002/chem.200903294. PubMed DOI

Mersch C, Wagner S, Hoffmann-Röder A. Synlett. 2009:2167–2171. doi: 10.1055/s-0029-1217566. DOI

Johannes M, Oberbillig T, Hoffmann-Röder A. Org Biomol Chem. 2011;9:5541–5546. doi: 10.1039/c1ob05373f. PubMed DOI

Stephenson E L, Zhang P, Ghorbani S, Wang A, Gu J, Keough M B, Rawji K S, Silva C, Yong V W, Ling C-C. ACS Cent Sci. 2019;5:1223–1234. doi: 10.1021/acscentsci.9b00327. PubMed DOI PMC

Nishimura S-I, Hato M, Hyugaji S, Feng F, Amano M. Angew Chem, Int Ed. 2012;51:3386–3390. doi: 10.1002/anie.201108742. PubMed DOI

van Wijk X M, Lawrence R, Thijssen V L, van den Broek S A, Troost R, van Scherpenzeel M, Naidu N, Oosterhof A, Griffioen A W, Lefeber D J, et al. FASEB J. 2015;29:2993–3002. doi: 10.1096/fj.14-264226. PubMed DOI PMC

Keough M B, Rogers J A, Zhang P, Jensen S K, Stephenson E L, Chen T, Hurlbert M G, Lau L W, Rawji K S, Plemel J R, et al. Nat Commun. 2016;7:11312. doi: 10.1038/ncomms11312. PubMed DOI PMC

Qin K, Zhang H, Zhao Z, Chen X. J Am Chem Soc. 2020;142:9382–9388. doi: 10.1021/jacs.0c02110. PubMed DOI

Wang L-X, Sakairi N, Kuzuhara H. J Chem Soc, Perkin Trans 1. 1990:1677–1682. doi: 10.1039/p19900001677. DOI

Kurfiřt M, Červenková Št’astná L, Dračínský M, Müllerová M, Hamala V, Cuřínová P, Karban J. J Org Chem. 2019;84:6405–6431. doi: 10.1021/acs.joc.9b00705. PubMed DOI

Lin P-C, Adak A K, Ueng S-H, Huang L-D, Huang K-T, Ho J-a A, Lin C-C. J Org Chem. 2009;74:4041–4048. doi: 10.1021/jo900516r. PubMed DOI

Dax K, Albert M, Hammond D, Illaszewicz C, Purkarthofer T, Tscherner M, Weber H. Rearrangements in the Course of Fluorination by Diethylaminosulfur Trifluoride at C-2 of Glycopyranosides: Some New Parameters. In: Schmid W, Stütz A E, editors. Timely Research Perspectives in Carbohydrate Chemistry. Vienna, Austria: Springer; 2002. pp. 77–98. DOI

Karban J, Císařová I, Strašák T, Šťastná L Č, Sýkora J. Org Biomol Chem. 2012;10(2):394–403. doi: 10.1039/c1ob06336g. PubMed DOI

Lainé D, Denavit V, Lessard O, Carrier L, Fecteau C-É, Johnson P A, Giguère D. Beilstein J Org Chem. 2020;16:2880–2887. doi: 10.3762/bjoc.16.237. PubMed DOI PMC

Quiquempoix L, Wang Z, Graton J, Latchem P G, Light M, Le Questel J-Y, Linclau B. J Org Chem. 2019;84:5899–5906. doi: 10.1021/acs.joc.9b00310. PubMed DOI

Baer H H, Mateo F H, Siemsen L. Carbohydr Res. 1989;187:67–92. doi: 10.1016/0008-6215(89)80056-4. PubMed DOI

Popsavin V, Benedeković G, Popsavin M, Divjaković V, Armbruster T. Tetrahedron. 2004;60:5225–5235. doi: 10.1016/j.tet.2004.04.040. DOI

Chen S Y, Joullie M M. J Org Chem. 1984;49:1769–1772. doi: 10.1021/jo00184a020. DOI

Vera-Ayoso Y, Borrachero P, Cabrera-Escribano F, Gómez-Guillén M. Tetrahedron: Asymmetry. 2005;16:889–897. doi: 10.1016/j.tetasy.2004.12.024. DOI

Vera-Ayoso Y, Borrachero P, Cabrera-Escribano F, Carmona A T, Gómez-Guillén M. Tetrahedron: Asymmetry. 2004;15:429–444. doi: 10.1016/j.tetasy.2003.11.034. DOI

Suzuki K, Ito Y, Kanie O. Carbohydr Res. 2012;359:81–91. doi: 10.1016/j.carres.2012.07.003. PubMed DOI

Herczeg M, Mező E, Eszenyi D, Lázár L, Csávás M, Bereczki I, Antus S, Borbás A. Eur J Org Chem. 2013:5570–5573. doi: 10.1002/ejoc.201300681. DOI

Card P J, Reddy G S. J Org Chem. 1983;48:4734–4743. doi: 10.1021/jo00172a054. DOI

Kolakowski R V, Shangguan N, Sauers R R, Williams L J. J Am Chem Soc. 2006;128:5695–5702. doi: 10.1021/ja057533y. PubMed DOI

Dhakal B, Crich D. J Am Chem Soc. 2018;140:15008–15015. doi: 10.1021/jacs.8b09654. PubMed DOI PMC

Wray V. J Chem Soc, Perkin Trans 2. 1976:1598–1605. doi: 10.1039/p29760001598. DOI

Phillips L, Wray V. J Chem Soc B. 1971:1618–1624. doi: 10.1039/j29710001618. DOI

Denavit V, Lainé D, Bouzriba C, Shanina E, Gillon É, Fortin S, Rademacher C, Imberty A, Giguère D. Chem – Eur J. 2019;25:4478–4490. doi: 10.1002/chem.201806197. PubMed DOI

Influence of Selective Deoxyfluorination on the Molecular Structure of Type-2 N-Acetyllactosamine