Efficient Synthesis of Spacer-linked Dimers of N-Acetyllactosamine Using Microvawe-assisted Pyridinium Triflate-promoted Glycosylations with Oxazoline Donors

Abstract

Application of pyridinum triflate as promoter combined with microwave heating afforded an easy and efficient synthesis of spacer-linked dimers of LacNAc from the corresponding oxazoline donor. As compared to the promoter pyridinium p-toluenesulfonate the triflate salt increased the yield of dimers with more than 30%, whereas microwave heating improved the yields with a further 15%.

Key words

glycoside - glycosylations - oligosaccharides

References

• 1 Leffler H. Trends Glycosci. Glycotechnol.  1997,  9:  9 
• 2 Perillo NL. Marcus ME. Baum LG. J. Mol. Med.  1998,  76:  402 
• 3 Danguy A. Camby I. Kiss R. Biochim. Biophys. Acta  2002,  1572:  285 
• 4 Rabinovich GA. Rubinstein N. Toscano MA. Biochim. Biophys. Acta  2002,  1572:  274 
• 5 Nangia-Makker P. Baccarini S. Raz A. Curr. Top. Biochem. Res.  2000,  3:  229 
• 6 Brewer F. Biochim. Biophys. Acta  2002,  1572:  255 
• 7 Banoub J. Boullanger P. Lafont D. Chem. Rev.  1992,  92:  1167 
• 8 Yohino T. Sato K.-I. Wanme F. Takai I. Ishido Y. Glycoconj. J.  1992,  9:  287 
• 9 Wittman W. Lennartz D. Eur. J. Org. Chem.  2002,  1363 
• 11 Söderberg E. Westman J. Oscarson S. J. Carbohydr. Chem.  2001,  20:  397 

10

All new compounds were identified and characterized by ¹H NMR, ¹³C NMR and MALDI-TOF MS.

12

General Procedure for the Synthesis of Dimers Using Microwave Heating: Oxazoline 1 (0.22 mmol), pyridinium triflate (0.22 mmol) and the diol (0.1 mmol) were dissolved in (CH₂Cl)₂ (1 mL) and heated in a sealed vessel in a Smithsynthesizer, a single mode microwave cavity from Personal Chemistry, with a set cut-off temperature of 80 °C for 20 min. Purification directly on a silica gel column (EtOAc/MeOH) gave products 7-10 (62-71%).