In vivo, sugar chains (oligosaccahrides) having a variety of structures are synthesized through successive bonding of sugar residues in a stereo-specific and regio-specific manner by the mediation of a sugar nucleotide serving as a sugar donor and glycosyltransferase. For example, in the case where certain cells undergo malignant alteration, in one conceivable mechanism, a new glycosyltransferase is expressed, or the balance of glycosyltransferases is varied, whereby a portion of the sugar chain structure is modified, and the sugar chain is elongated or modified, to form a tumor marker.
Thus, intentional modification of sugar chains present on cell surfaces is envisaged to change the nature and functions which the cells per se have, and many attempts have been extensively made to synthesize artificial, novel sugar chains in order to confirm the potential of the modified sugar chains.
In one means for synthesizing an artificial sugar chain, an artificial sugar nucleotide in which the structure of the sugar moiety has been modified is employed as a sugar donor in glycosyltransferase reaction, to thereby synthesize an artificial sugar chain.
One conceivable artificial sugar nucleotide is a sugar nucleotide whose hydroxyl groups have similar properties to those of a native sugar nucleotide and in which an inert halogen atom has been introduced. For example, the present inventors previously prepared fluorinated aminosugar nucleotides by introducing a fluorine atom to a hydroxyl group of N-acetylglucosamine and N-acetylgalactosamine, which are well known as essential compositional units of physiologically active sugar chains, and studied the properties of the products (Patent Document 1).
Similar to N-acetylglucosamine and N-acetylgalactosamine, regarding galactose, which is an essential component of a physiologically active sugar chain, a 4-position fluorinated galactose sugar nucleotide (Non-Patent Documents 1 and 2) and a galactose sugar nucleotide in which a fluorine atom has been introduced to a position other than the 4-position (Non-Patent Documents 3 to 5) were previously prepared.
Patent Document 1: JP-A-2004-168751
Non-Patent Document 1: J. Org. Chem., 59, 6994-6998 (1994)
Non-Patent Document 2: J. Chem. Soc., Perkin Trans. 1, 2375-2382 (1997)
Non-Patent Document 3: Bioorg. Med. Chem. 5, 497-500 (1997)
Non-Patent Document 4: Carbohydr. Res., 328, 473-480 (2000)
Non-Patent Document 5: Tetrahedron Letters. 34. (40), 6419-6422 (1993)