10.1002/chem.201801083
Chemistry - A European Journal
FULL PAPER
1.32. HRMS Calcd for [C20H29N6O14P+ H]+ 609.1552, Found
609.1556
[6] (a) Y. Zhu, X. Shan, S. A. Yuzwa, D. J. Vocadlo, J. Biol. Chem. 2014, 289,
34472-34481. (b) S. A. Yuzwa, D. J. Vocadlo, Chem. Soc. Rev. 2014, 43,
6839-6858.
Compound 20. Sticky oil. [α]D25 ≅ +70 (c 2.4, H2O). 1H NMR (400
MHz; DMSO-d6): =8.16 (s, 1H, C=CH-N); 7.90 (d, 1H, J=8.1 Hz,
[7] X.-L. Sun, Med. Chem. 2013, 3, e106.
[8] (a) S. Wang, S. Vidal, Carbohydr. Chem. 2013, 39, 78-101. (b) R.
Roychoudhury, N. L. B. Pohl, Curr. Opin. Chem. Biol. 2010, 14, 168-173.
(c) J. Schutzbach, I. Brockhausen, Methods in Molecular Biology (Totowa,
NJ, United States) 2009, 534, 359-373. (d) E. Walker-Nasir, I. Ahmad, M.
Saleem, D. C. Hoessli, Curr. Org. Chem. 2007, 11, 591-607. (e) K.-H.
Jung, R. R. Schmidt, Carbohydr.-Based Drug Discov. 2003, 2, 609-659.
[9] T. Kajimoto, M. Node, Synthesis 2009, 3179-3210.
[10] (a) X. Qian, M. M. Palcic, Carbohydr. Chem. Biol. 2000, 3, 293-312. (b) L.
J. Whalen, W. A. Greenberg, M. L. Mitchell, C.-H. Wong, Iminosugars
2007, 153-176. (c) L. Cipolla, B. La Ferla, M. Gregori, Comb. Chem. High
Throughput Screening 2006, 9, 571-582. (d) P. Compain, O. R. Martin,
Bioorg. Med. Chem. 2001, 9, 3077-3092.
[11] P. Merino, I. Delso, T. Tejero, M. Ghirardello, V. Juste-Navarro, Asian J.
Org. Chem. 2016, 5, 1413-1427
[12] (a) L. Tedaldi, G. K. Wagner, MedChemComm 2014, 5, 1106-1125. (b) J.
Jiang, M. B. Lazarus, L. Pasquina, P. Sliz, S. Walker, Nat. Chem. Biol.
2012, 8, 72-77.
[13] (a) D. A. Smithen, S. M. Forget, N. E. McCormick, R. T. Syvitski, D. L.
Jakeman, Org. Biomol. Chem. 2015, 13, 3347-3350. (b) M. Izumi, H.
Yuasa, H. Hashimoto, Curr. Top. Med. Chem. 2009, 9, 87-105.
[14] (a) S. Wang, J. A. Cuesta-Seijo, D. Lafont, M. M. Palcic, S. Vidal, Chem.
Eur. J. 2013, 19, 15346-15357. (b) S. Wang, J. A. Cuesta-Seijo, A.
Striebeck, D. Lafont, M. M. Palcic, S. Vidal, ChemPlusChem 2015, 80,
1525-1532.
[15] M. Ghirardello, M. de las Rivas, A. Lacetera, I. Delso, E. Lira-Navarrete,
T. Tejero, S. Martin-Santamaria, R. Hurtado-Guerrero, P. Merino, Chem.
Eur. J. 2016, 22, 7215-7224.
[16] (a) E. Lira-Navarrete, M. d. l. Rivas, I. Companon, M. C. Pallares, Y. Kong,
J. Iglesias-Fernandez, G. a. J. L. Bernardes, J. M. Peregrina, C. Rovira,
P. Bernado, P. Bruscolini, H. Clausen, A. Lostao, F. Corzana, R. Hurtado-
Guerrero, Nat. Commun. 2015, 6, 6937. (b) R. Hurtado-Guerrero,
Biochem. Soc. Trans. 2016, 44, 61-67. (c) D. Madariaga, N. Martinez-
Saez, V. J. Somovilla, L. Garcia-Garcia, M. Alvaro Berbis, J. Valero-
Gonzalez, S. Martin-Santamaria, R. Hurtado-Guerrero, J. L. Asensio, J.
Jimenez-Barbero, A. Avenoza, J. H. Busto, F. Corzana, J. M. Peregrina,
Chem. Eur. J. 2014, 20, 12616-12627.
[17] (a) S. Pathak, J. Alonso, M. Schimpl, K. Rafie, D. E. Blair, V. S. Borodkin,
A. W. Schuttelkopf, O. Albarbarawi, D. M. F. van Aalten, Nat. Struct. Mol.
Biol. 2015, 22, 744-750. (b) Y. Zhu, T.-W. Liu, S. Cecioni, R. Eskandari,
W. F. Zandberg, D. J. Vocadlo, Nat. Chem. Biol. 2015, 11, 319-325. (c)
M. B. Lazarus, J. Jiang, T. M. Gloster, W. F. Zandberg, G. E. Whitworth,
D. J. Vocadlo, S. Walker, Nat. Chem. Biol. 2012, 8, 966-968. (d) A.
Ostrowski, D. M. F. van Aalten, Biochem. J. 2013, 456, 1-12.
[18] T. M. Gloster, D. J. Vocadlo, Curr. Signal Transduct. Ther. 2010, 5, 74-
91.
+
H-6); 7.82 (d, 1H, J=6.9 Hz, NHAc); 7.30 (bs, 4H, NH4 ); 6.22 (d,
1H, J=5,8 Hz, H-1g); 5.78 (d, 1H, J=5.7 Hz, H-1’); 5.58 (d, 1H,
J=8.1 Hz, H-5); 4.80-4.71 (m, 2H, CH2OP); 4.25 (dd, 1H, J=10.8,
8.5 Hz, H-3g); 4.10-4.03 (m, 2H, H-2’, H-2g); 4.03-3.98 (m, 1H, H-
3’); 3.95-3.90 (m, 1H, H-4’); 3.88-3.76 (m, 2H, H-5A’ e H-5B’); 3.53
(dd, 1H, H=14, 4.7 Hz, H-6Ag); 3.47-3.40 (m, 2H, H-5g e H-6Bg);
3.32 (t, 1H, J=8.9 Hz, H-4g); 1.67 (s, 3H, Ac). 13C-NMR (101 MHz;
DMSO-d6): =170.4 (Ac); 163.2 (C=O); 150.9 (C=O); 144.4 (=C-
N); 141.0 (CH-5u); 125.8 (=CH-N); 102.0 (CH-6u); 87.5(CH-1’);
83.6 (CH-4’); 83.0 (CH-1g); 76.2 (CH); 73.4 (CH); 73.0 (CH); 70.5
(CH); 70.2 (CH); 64.4 (CH2); 60.6 (CH2); 57.9 (CH2); 53.4 (CH-
2g); 22.3 (CH3). 31P-NMR (122 MHz; DMSO-d6): =-1.35. HRMS
Calcd for [C20H29N6O14P+ H]+ 609.1552, found 609.1556
Acknowledgements
We thank for their support of our programs: MINECO (Madrid,
Spain) and FEDER Program (Project CTQ2016-76155-R) and the
Government of Aragon (Group E-10) to P.M. A Wellcome
Investigator Award (110061) to DMFvA. The Universty of Ferrara
(FAR2016) to D.P. and M.F. M.G. thanks MECD for a FPU pre-
doctoral grant. D.S. thanks CSIC for a JAE-Pre pre-doctoral grant.
KR is funded by a BBSRC Studentship (1416998). Dr. T. Bernardi
(University of Ferrara) is acknowledged for ESI-HRMS analysis
Author Contribution
P.M., T.T. and I.D. conceived and planned the experiments. M.G.
designed and performed the synthesis of compounds 7-15. D.S.
performed the synthesis of 16. D.P., N.C, E.M. and M.F. designed
and performed the synthesis of compounds 17-20. P.M.
performed docking calculations. I.D. performed molecular
dynamic simulations and STD NMR experiments. D.M.F.v.A. and
K.R. performed biological assays. P.M. wrote the manuscript with
support from D.M.F.v.A., T.T., K.R and I.D.
[19] (a) B. J. Gross, B. C. Kraybill, S. Walker, J. Am. Chem. Soc. 2005, 127,
14588-14589. (b) H. C. Dorfmueller, V. S. Borodkin, D. E. Blair, S. Pathak,
I. Navratilova, D. M. F. Aalten, Amino Acids 2011, 40, 781-792.
[20] (a) S. Wang, D. L. Shen, D. Lafont, A.-S. Vercoutter-Edouart, M.
Mortuaire, Y. Shi, O. Maniti, A. Girard-Egrot, T. Lefebvre, B. M. Pinto, D.
Vocadlo, S. Vidal, MedChemComm 2014, 5, 1172-1178. (b) A. K. Nagel,
L. E. Ball, Amino Acids 2014, 46, 2305-2316.
[21] R. Trapannone, K. Rafie, D. M. F. van Aalten, Biochem. Soc. Trans. 2016,
44, 88-93.
[22] (a) M. Mitchell, L. Qaio, C.-H. Wong, Adv. Synth. Catal. 2001, 343, 596-
599. (b) M. D. Burkart, S. P. Vincent, A. Duffels, B. W. Murray, S. V. Ley,
C. H. Wong, Bioorg. Med. Chem. 2000, 8, 1937-1946. (c) P. Merino, I.
Delso, T. Tejero, M. Ghirardello, V. Juste-Navarro, Asian J. Org. Chem.
2016. (d) P. Merino, T. Tejero, I. Delso, R. Hurtado-Guerrero, A. Gomez-
SanJuan, D. Sadaba, Mini-Rev. Med. Chem. 2012, 12, 1455-1464.
[23] A. Ardevol, C. Rovira, J. Am. Chem. Soc. 2015, 137, 7528-7547.
[24] K. K. Yeoh, T. D. Butters, B. L. Wilkinson, A. J. Fairbanks, Carbohydr.
Res. 2009, 344, 586-591.
[25] I. Delso, T. Tejero, A. Goti, P. Merino, Tetrahedron 2010, 66, 1220-1227.
[26] P. Merino, I. Delso, V. Mannucci, T. Tejero, Tetrahedron Lett. 2006, 47,
3311-3314.
[27] A. Dondoni, S. Staderini, A. Marra, Eur. J. Org. Chem. 2013, 5370-5375.
[28] (a) M. G. Finn, V. V. Fokin, Chem. Soc. Rev. 2010, 39, 1231-1232. (b) H.
C. Kolb, M. G. Finn, K. B. Sharpless, Angew. Chem., Int. Ed. 2001, 40,
2004-2021. (c) C. Wang, D. Ikhlef, S. Kahlal, J.-Y. Saillard, D. Astruc,
Coord. Chem. Rev. 2016, 316, 1-20. (d) L. Liang, D. Astruc, Coord. Chem.
Rev. 2011, 255, 2933-2945.
Keywords: glycosyltransferases • OGT • Nucleotide
diphosphate analogues • Carbohydrates • Bioconjugates
[1] (a) J. Voglmeir, S. L. Flitsch, Sci. Synth., Biocatal. Org. Synth. 2015, 1,
507-542. (b) D.-M. Liang, J.-H. Liu, H. Wu, B.-B. Wang, H.-J. Zhu, J.-J.
Qiao, Chem. Soc. Rev. 2015, 44, 8350-8374. (c) M. M. Palcic, Curr. Opin.
Chem. Biol. 2011, 15, 226-233.
[2] S. Kellokumpu, A. Hassinen, T. Glumoff, Cell. Mol. Life Sci. 2016, 73, 305-
325.
[3] (a) D. Horton, in Carbohydrate Chemistry, Biology and Medical
Applications (Eds.: M. K. Cowman, C. A. Hales), Elsevier, Oxford, 2008,
pp. 1-28. (b) R. W. Gantt, P. Peltier-Pain, W. J. Cournoyer, J. S. Thorson,
Nat. Chem. Biol. 2011, 7, 685-691. (c) C. Zhang, B. R. Griffith, Q. Fu, C.
Albermann, X. Fu, I.-K. Lee, L. Li, J. S. Thorson, Science 2006, 313, 1291-
1294.
[4] M. E. Etzler, A. Varki, R. L. Cummings, J.D. Esko, H. H. Freeze, G. W.
Hart, Essentials of Glycobiology, 2nd Ed. Cold Spring Harbor Laboratory
Press, New York, 2008.
[29] V. K. Tiwari, B. B. Mishra, K. B. Mishra, N. Mishra, A. S. Singh, X. Chen,
Chem. Rev. 2016, 116, 3086-3240.
[5] (a) Z. Ma, K. Vosseller, Amino Acids 2013, 45, 719-733. (b) T. P. Lynch,
M. J. Reginato, Cell Cycle 2011, 10, 1712-1713.
[30] (a) S. L. Beaucage, M. H. Caruthers, Tetrahedron Lett. 1981, 22, 1859-
1862. (b) M. H. Caruthers, S. L. Beaucage, C. Becker, J. W. Efcavitch, E.
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