compounds for testing the donor substrate specificity of
diverse GlcNAc-transferases.
This work was supported by NIH grant R01HD065122,
NSF grants CHE-0548235 and CHE-1012511. X. Chen is a
Camille Dreyfus Teacher-Scholar and a UC-Davis Chancellor’s
Fellow.
Notes and references
1 H. J. M. Gijsen, L. Qiao, W. Fitz and C.-H. Wong, Chem. Rev.,
1996, 96, 443–474.
2 H. Yu and X. Chen, Org. Biomol. Chem., 2007, 5, 865–872.
3 X. Chen, ACS Chem. Biol., 2011, 6, 14–17.
4 J. Yang, X. Fu, J. Liao, L. Liu and J. S. Thorson, Chem. Biol.,
2005, 12, 657–664.
5 H. Yu, S. Huang, H. Chokhawala, M. Sun, H. Zheng and X. Chen,
Angew. Chem., Int. Ed., 2006, 45, 3938–3944.
6 K. Lau, V. Thon, H. Yu, L. Ding, Y. Chen, M. M. Muthana,
D. Wong, R. Huang and X. Chen, Chem. Commun., 2010, 46,
6066–6068.
7 S. J. Danishefsky and M. T. Bilodeau, Angew. Chem., Int. Ed.
Engl., 1996, 35, 1380–1419.
8 M. Oberthur, C. Leimkuhler and D. Kahne, Org. Lett., 2004, 6,
2873–2876.
¨
9 K. Toshima and K. Tatsuta, Chem. Rev., 1993, 93, 1503–1531.
10 U. Lindahl and M. Hook, Annu. Rev. Biochem., 1978, 47, 385–417.
11 K. Honke and N. Taniguchi, Med. Res. Rev., 2002, 22, 637–654.
12 J. L. Funderburgh, Glycobiology, 2000, 10, 951–958.
13 C. Mitsuoka, M. Sawada-Kasugai, K. Ando-Furui, M. Izawa,
H. Nakanishi, S. Nakamura, H. Ishida, M. Kiso and R. Kannagi,
J. Biol. Chem., 1998, 273, 11225–11233.
14 N. Kimura, C. Mitsuoka, A. Kanamori, N. Hiraiwa,
K. Uchimura, T. Muramatsu, T. Tamatani, G. S. Kansas and
R. Kannagi, Proc. Natl. Acad. Sci. U. S. A., 1999, 96, 4530–4535.
15 K. Uchimura, J. M. Gauguet, M. S. Singer, D. Tsay, R. Kannagi,
T. Muramatsu, U. H. von Andrian and S. D. Rosen, Nat.
Immunol., 2005, 6, 1105–1113.
16 B. S. Bochner, R. A. Alvarez, P. Mehta, N. V. Bovin, O. Blixt,
J. R. White and R. L. Schnaar, J. Biol. Chem., 2005, 280,
4307–4312.
17 H. Tateno, P. R. Crocker and J. C. Paulson, Glycobiology, 2005,
15, 1125–1135.
18 Y. Li, H. Yu, Y. Chen, K. Lau, L. Cai, H. Cao, V. K. Tiwari,
J. Qu, V. Thon, P. G. Wang and X. Chen, Molecules, 2011, 16,
6396–6407.
19 M. Nishimoto and M. Kitaoka, Appl. Environ. Microbiol., 2007,
73, 6444–6449.
20 L. Cai, W. Guan, M. Kitaoka, J. Shen, C. Xia, W. Chen and
P. G. Wang, Chem. Commun., 2009, 2944–2946.
21 L. Cai, W. Guan, W. Wang, W. Zhao, M. Kitaoka, J. Shen,
C. O’Neil and P. G. Wang, Bioorg. Med. Chem. Lett., 2009, 19,
5433–5435.
22 J. Fang, W. Guan, L. Cai, G. Gu, X. Liu and P. G. Wang, Bioorg.
Med. Chem. Lett., 2009, 19, 6429–6432.
23 G. Zhao, W. Guan, L. Cai and P. G. Wang, Nat. Protoc., 2010, 5,
636–646.
24 W. Guan, L. Cai and P. G. Wang, Chemistry, 2010, 16, 13343–13345.
25 L. Cai, L. Ban, W. Guan, M. Mrksich and P. G. Wang, Carbohydr.
Res., 2011, 346, 1576–1580.
26 L. Cai, W. Guan, W. Chen and P. G. Wang, J. Org. Chem., 2010,
75, 3492–3494.
Scheme 2 Chemical diversification at (A) the C-2 of glucosamine and
(B) the C-6 of N-acetylglucosamine in UDP-sugar nucleotides.
Reagents and conditions: (a) K2CO3, CH3OH, H2O, 20 1C, overnight,
98%; (b) PyꢀSO3, 2 M NaOH, H2O, overnight, 86%; (c) RCOCl,
NaHCO3, CH3CN, H2O; (d) NaOMe, MeOH; (e) H2, Pd/C, MeOH,
H2O, 1 h, 96%.
23 using various acyl chlorides produced C-6 modified
UDP-GlcNAc derivatives including UDP-6-acetoxyacetamido-
N-acetylglucosamine (UDP-GlcNAc6NGcAc, 24), UDP-
6-azidoacetamido-N-acetylglucosamine (UDP-GlcNAc6NAz,
26), UDP-6-phenylacetamido-N-acetylglucosamine (UDP-
GlcNAc6NPhAc, 27), and UDP-N-(1,10-biphenyl-4-yl)-
acetamido-N-acetylglucosamine (UDP-GlcNAc6NPh2Ac, 28)
in 61–91% yields. Finally, C-6 modified derivative UDP-N-
hydroxyacetamido-N-acetylglucosamine (UDP-GlcNAc6NGc, 25)
was obtained in 98% yield by treating compound 24 in
NaOMe and methanol.
In summary, we have developed a highly efficient chemo-
enzymatic approach for producing a series of UDP-GlcNAc
derivatives containing diverse natural and non-natural
modification at C-2 or C-6 of the glucosamine moiety using
a combination of one-pot three-enzyme system followed
by parallel chemical diversification. The obtained UDP-
glucosamine derivatives containing natural occurring
GlcNAc, 6-O-sulfo-GlcNAc, N-sulfo-glucosamine, and non-
natural C2- or C6-modified GlcNAc analogues are excellent
c
This journal is The Royal Society of Chemistry 2011
Chem. Commun., 2011, 47, 10815–10817 10817