Earlier we reported a convenient and efficient method of preparing
Sialic acid family comprises over 40 neuraminic acid versions and monosaccharide derivatives; the number of biologically relevant sialic acid oligosaccharides is also very high. Sialic acids are a part of the most important molecules of life, since they occupy the terminal position on cell membrane glycoproteins and glycolipids. Given their location and ubiquitous distribution, sialic acids can mediate or modulate a wide range of physiological and pathological processes and play a role not only in the protection and adaptation of life, but also in being utilized by life-threatening infectious microorganisms [
Peracetylated methyl esters of Neu5Gc (
2-Chloroderivatives
Glycosylation was performed in dry CH2Cl2 in the presence of Ag2CO3 or Ag2CO3/AgOTf (silver trifluoromethanesulfonate) and molecular sieves 4Å (MS 4Å) at room temperature for 1–7 days; the reaction conditions and yields are given in the Table
Sialylation with neuraminic acid derivatives.
# | Sug-Cl | ROH | ROH/ | Ag2CO3/ | AgOTf/ | Time, | Sug-OR | |||
1 | Neu5Ac ( | HO(CH2)3NHCOCF3 | 5 | 2 | — | 2.6 (62 h) | 71 | 71 | ||
HO(CH2)3NHCOCF3 | 2 | 3 | 0.1 | 0.2 (5 h) | 47 | 36 | 95 : 5 | |||
3 | Neu5Gc ( | HO(CH2)3NHCOCF3 | 3 | 3 | — | 3 | 68 | 57 | 92 : 8 | |
4 | 4′,6′-diol-LacNAc | 1 | 3 | 0.1 | 7 | 30 | 12 | 43 : 57 | ||
5 | 9-deoxy-9-NAc- | HO(CH2)3NHCOCF3 | 1 | 3 | — | 3 | n.d. | 29 | Traces of | |
6 | 4′,6′-diol-LacNAc | 1 | 6 | — | 5 | n.d. | 25 | Traces of | ||
7 | Neu5Ac2-8 | HO(CH2)3NHCOCF3 | 2 | 3 | — | 7 | 20 | not done | 94 : 6 | |
8 | Neu5Ac 2-8 | HO(CH2)3NHCOCF3 | 2 | 3 | 0.1 | 1 | 36 | 32 | 90 : 10 | |
9 | ( | MeOH | 100 | 6 | 0.15 | 3 | n.d. | 40 | Traces of | |
10 | HOCH2( | 2 | 5 | 3 | 20 | 10 | 50 : 50 | |||
11 | HOCH2( | 4 | 6 | 0.6 | 3 | 32 | 12 | 39 : 61 | ||
12 | Neu5Ac2-8 | HO(CH2)3NHCOCF3 | 3 | 3 | 7 | 33 | 27 | 81 : 19 | ||
13 | HO(CH2)3NHCOCF3 | 3 | 3 | 0.5 | 7 | 37 | not done | 67 : 33 |
All Sug-Cl (see Table
Glycosylation with chloride of Neu5Gc (
(a) MeOH/HCl; (b) Ac2O/Py; (c) AcCl, MeOH/CHCl3; (d) Ag2CO3 (Ag2CO3/AgOTf), CH2Cl2, MS 4Å; (e) MeONa/MeOH; (f) NaOH/H2O; (g) H2, Pd/C.
Glycosylation of 4′,6′-diol of
Glycosylation with chloride of 9-deoxy-9-NAc-Neu5Ac
(a) MeOH/HCl; (b) Ac2O/Py; (c) AcCl, MeOH/CHCl3; (d) Ag2CO3, CH2Cl2, MS 4Å; (e) MeONa/MeOH; (f) NaOH/H2O.
Methylation followed by acetylation of Neu5Ac
(a) MeOH/HCl; (b) Ac2O/Py; (c) AcCl, MeOH/CHCl3; (d) Ag2CO3/AgOTf, CH2Cl2, MS 4Å; (e) MeONa/MeOH; (f) NaOH/H2O; (g) CF3COOH.
(a) MeOH/HCl; (b) Ac2O/Py; (c) AcCl, MeOH/CHCl3; (d) Ag2CO3/AgOTf, CH2Cl2, MS 4Å; (e) MeONa/MeOH; (f) NaOH/H2O.
Glycosylation with Neu5Ac
In case of
Trisialic chlorides
The structure of all the studied compounds was confirmed by high resolution 1H NMR data. Spectra of derivatives
Neu5Ac was from Juelich Enzyme Products GmbH (Wiesbaden, Germany); 9-deoxy-9-NAc-Neu5Ac was obtained as described in [
Neuraminic acid derivative (0.5 mmol of
Peracetylated methyl ester of neuraminic acid derivative (1 mmol of
A solution of Sug-Cl (0.1 mmol) in dry CH2Cl2 (3 ml) and AgOTf (0.01–0.06 mmol) were added to a mixture of acceptor (0.1–0.4 mmol), Ag2CO3 (0.3–0.6 mmol), and MS 4Å (1 g) in dry methylene chloride (5 ml). The reaction mixture was stirred at room temperature (20–25°C) for 0.2–7 days (reaction completion was determined by disappearing of Sug-Cl according to TLC). The reaction mixture was filtered, the residue was washed with CHCl3/MeOH (1 : 1); the combined filtrate was evaporated, coevaporated with toluene, and dried
(see Table
(a) Procedure for
(b) Procedure for
(c) Synthesis of
(d) Procedure for
(e) Synthesis of
1H NMR spectra were recorded at 30°C with a Varian 600 MHz instrument. Mass spectra (MALDI-TOF) were recorded on a Vision 2000 mass spectrometer. Optical rotations were measured with a JASCO DIP-360 polarimeter at 20°C. Thin-layer chromatography was performed using silica gel 60 F254 aluminum sheets (Merck, 1.05554) with detection by charring after 7% H3PO4 soaking, or ninhydrine.
1H NMR spectrum (D2O, 303 K, 600 MHz)
This work was supported with FP6 (project “Avian influenza: impact of virus-host interactions on pathogenesis and ecology”, acronym: FLUPATH, contract No. 044220) and Grant of Russian Foundation for Basic Research 07-04-00630.