Subscribe to RSS
DOI: 10.1055/s-2006-947338
New Oligosaccharide Analogues: Non-Glycosidically Linked Thioether-Bridged Pseudodisaccharides
Publication History
Publication Date:
04 July 2006 (online)
![](https://www.thieme-connect.de/media/synlett/200611/lookinside/thumbnails/10.1055-s-2006-947338-1.jpg)
Abstract
The synthesis of six disaccharide analogues is reported. The pseudodisaccharides each consist of two monosaccharide residues linked non-glycosidically via a thioether functionality; both C 2-symmetric and unsymmetrically substituted examples are described. The synthesis was achieved by first introducing an acetate-protected sulfur into partially protected carbohydrates by SN2 displacement of sulfonate esters by thioacetate. Deacetylation of the sulfur was followed by treatment with another carbohydrate sulfonate derivative, and a second SN2 displacement gave the pseudodisaccharide products.
Key words
carbohydrates - sulfur - stereoselective synthesis - coupling - pseudodisaccharides
- 1
Varki A. Glycobiology 1993, 3: 97 - 2
Karlsson K.-A. Curr. Opin. Struct. Biol. 1995, 5: 622 - 3
Kannagi R.Izawa M.Koike T.Miyazaki K.Kimura N. Cancer Sci. 2004, 95: 377 -
4a
Postema MHD.Piper JL.Betts RL. Synlett 2005, 1345 -
4b
Postema MHD. Tetrahedron 1992, 48: 8545 -
4c
Levy DE.Tang C. The Chemistry of C-Glycosides 1st ed. Vol. 13: Elsevier Science; Oxford: 1995. -
4d
Meo P.Osborn HMI. In CarbohydratesOsborn HMI. Academic Press; New York: 2003. p.337 -
5a
Pachamuthu K.Schmidt RR. Chem. Rev. 2006, 106: 160 -
5b
Driguez H. ChemBioChem 2001, 2: 311 -
5c
Fairweather JK.Driguez H. Carbohydrates in Chemistry and Biology Vol. 1:Ernst B.Hart GW.Sinay P. Wiley-VCH; Weinheim: 2000. p.531-564 - 6
Vázquez-Camposa S.St. Hilaire PM.Damgaarda D.Meldal M. QSAR Comb. Sci. 2005, 24: 923 -
7a
Cumpstey I.Sundin A.Leffler H.Nilsson UJ. Angew. Chem. 2005, 44: 5110 -
7b
Leffler H.Barondes S. J. Biol. Chem. 1986, 261: 10119 -
7c
Bianchet MA.Ahmed H.Vasta GR.Amzel LM. Proteins 2002, 40: 378 - 8
Geyer A.Reinhardt S.Bendas G.Rothe U.Schmidt RR. J. Am. Chem. Soc. 1997, 119: 11707 -
9a
Kato A.Kato N.Kano E.Adachi I.Ikeda K.Yu L.Okamoto T.Banba Y.Ouchi H.Takahata H.Asano N. J. Med. Chem. 2005, 48: 2036 -
9b
Blériot Y.Gretzke D.Krülle TM.Butters TD.Dwek RA.Nash RJ.Asanod N.Fleet GWJ. Carbohydr. Res. 2005, 340: 2713 -
9c
Yu C.-Y.Asano N.Ikeda K.Wang M.-X.Butters TD.Wormald MR.Dwek RA.Winters AL.Nashe RJ.Fleet GWJ. Chem. Commun. 2004, 1936 - 10
Dahlgard M. J. Org. Chem. 1965, 30: 4352 - 11
Jesudason MV.Owen LN. J. Chem. Soc., Perkin Trans. 1 1974, 2019 - 12
Kojima M.Wanatabe M.Taguchi T. Tetrahedron Lett. 1968, 7: 839 - 13
Ihsiguro S.Tejima S. Chem. Pharm. Bull. 1968, 1567 - 14
Trimnell D.Stout EI.Doane WM.Russell CR. J. Org. Chem. 1975, 40: 1337 -
15a
Haines AH. Org. Biomol. Chem. 2004, 2: 2352 -
15b
Takahashi H.Fukuda T.Mitsuzuka H.Namme R.Miyamoto H.Ohkura Y.Ikegami S. Angew. Chem. Int. Ed. 2003, 42: 5069 -
15c
Pérez GS.Pérez G RM.Pérez G C.Zavala S MA.Vargas S R. Pharm. Acta Helv. 1997, 72: 105 -
15d
Hodosi G.Kovac P. Carbohydr. Res. 1998, 308: 63 -
15e
Farkas J.Sebesta K.Horska K.Samek Z.Dolejs L.Sorm F. Collect. Czech. Chem. Commun. 1969, 34: 1118 -
15f
Whistler RL.Frorein A. J. Org. Chem. 1961, 26: 3946 -
15g
Goueth PY.Ronco G.Villa P. J. Carbohydr. Chem. 1994, 13: 679 -
15h
Goueth PY.Fauvin M.Chelle-Regnaut I.Ronco G.Villa P. J. Carbohydr. Chem. 1994, 13: 697 - 16
Haradahira T.Maeda M.Omae H.Yano Y.Kojima M. Chem. Pharm. Bull. 1984, 32: 4758 - 17
Hall LD.Miller DC. Carbohydr. Res. 1976, 47: 299 - 18
Takeo K.Shibata K. Carbohydr. Res. 1984, 133: 147 - 19
Bernlind C.Oscarson S.Widmalm G. Carbohydr. Res. 1994, 263: 173 - 20
Contour-Galcera MO.Guillot JM.Ortiz-Mellet C.Pflieger-Carrara F.Defaye J.Gelas J. Carbohydr. Res. 1996, 281: 99
References and Notes
Typical Data - (Methyl 3- O -Benzyl-4,6- O -benzylidene-2-deoxy-β-d-mannopyranos-2-yl) (Methyl 2,3,4-Tri- O -benzyl-6-deoxy-α-d-mannopyranos-6-yl) Sulfane ( 12). A colourless oil; [α]D 23 -2.0 (c 0.5 in CHCl3). 1H NMR (400 MHz, CDCl3): δ = 2.98 (1 H, m, H-6a), 3.27-3.32 (2 H, m, H-5b, H-6′a), 3.34, 3.47 (6 H, 2 × s, 2 × OCH3), 3.55 (1 H, dd, J 1,2 = 1.5 Hz, J 2,3 = 4.4 Hz, H-2b), 3.76-3.88 (6 H, m, H-2a, H-3a, H-4a, H-5a, H-3b, H-6b), 4.07 (1 H, at, J = 9.4 Hz, H-4b), 4.28 (1 H, dd, J 5,6 ′ = 4.8 Hz, J 6,6 ′ = 10.4 Hz, H-6′b), 4.48 (1 H, d, H-1b), 4.60, 4.93 (2 H, ABq, J AB = 11.1 Hz, PhCH2), 4.60 (2 H, s, PhCH2), 4.69-4.80 (5 H, m, H-1a, 2 × PhCH2), 5.58 (1 H, s, PhCH), 7.21-7.48 (25 H, m, Ar-H). 13C NMR (100 MHz, CDCl3): δ = 36.1 (t, C-6a), 53.0 (d, C-2b), 55.0, 57.2 (2 × q, 2 × OCH3), 67.9 (d, C-5b), 68.8 (t, C-6b), 72.2, 72.4, 73.0, 75.2 (4 × t, 4 × PhCH2), 72.5, 75.0, 77.2, 78.1, 80.5 (5 × d, C-2a, C-3a, C-4a, C-5a, C-3b), 80.0 (d, C-4b), 99.0 (d, C-1a), 101.6 (d, PhCH), 103.2 (d, C-1b), 126.2, 127.7, 127.7, 127.8, 127.9, 128.0, 128.3, 128.4, 128.5, 129.0 (10 × d, Ar-CH), 137.7, 138.5, 138.5, 138.7, 138.5 (5 × s, 5 × Ar-C). MS (MALDI): m/z = 874 [M + K+], 858 [M + Na+].
22
Typical Procedure for the Formation of Thioether-Bridged Pseudodisaccharides.
Thioacetate 7-9 (0.1-0.4 mmol) was dissolved in MeOH (3 mL) and the solution was degassed and put under argon. MeONa (3 equiv) was added, and the mixture was stirred at r.t. After complete conversion to the thiol, as shown by TLC (approx 1 h), the mixture was poured into NH4Cl (30 mL of a sat. aq solution) and extracted with CH2Cl2 (2 × 20 mL). The combined organic extracts were dried (Na2SO4), filtered, and concentrated in vacuo. Sulfonate 1-3 (1.5 equiv) was dissolved in DMF (4 mL) and added to the crude thiol. NaH (60% in oil, 2 equiv) was added, and the mixture stirred at 50 °C under argon. After TLC showed the complete disappearance of thiol (approx. 30 min), the mixture was poured into NH4Cl (25 mL of a sat. aq solution) and extracted with Et2O (3 × 25 mL). The combined organic extracts were dried (Na2SO4), filtered, and concentrated in vacuo. The residue was purified by flash column chromatography (pentane, EtOAc) to afford the thioether-linked pseudodisaccharide 10-15 (see Table
[1]
).