9 シアロ糖鎖の合成研究(口頭発表の部)

抄録

N-Acetyl neuraminic acid (Neu5Ac (3)) is incorporated at the nonreducing terminal position of glycoconjugates which are found in cell membranes and in nervous systems of various living organisms. These sialyl conjugates play an essential role in biological molecular recognition processes, such as cell adhesion and differentiation phenomena. For the elucidation of these biological properties and functions, the supply of natural and nonnatural sialyl conjugates with a definite structures is indispensable. The ulosonic acids such as Neu5Ac (3), KDO (1), KDN (2) have the α-ketoacid moieties which exist in a 6-membered cyclic hemiacetal form. To establish a general synthetic method for monosaccharides containing the α-ketoacid structures, we examined the synthesis of Neu5Ac (3) utilizing alkylation of 2-alkoxy-2-cyanoacetate 20, an acylanion equivalent of alkyl glyoxylate, with bromide 19 derived from the commercially available D-glycero-D-gulo-heptose-1,4-lactone (11). We also examined the syntheses of KDO (1) and KDN (2) based on alkylation of 2-alkoxy-2-cyanoacetate 7 with the sugar-derived iodide 6 and triflate 15. One of the most difficult problem in the synthesis of sialyl conjugate is the stereoselective glycosidation of sialic acid with α-glycosidic linkage. First, we examined a new method for α-glycoside formation of sialyl conjugate utilizing the concept of "long-range participation". When 2-methylthioethyl ester was introduced into the carboxylic acid in the sialic acid as neighboring group and DME was used as solvent, highly α-selective glycosylation was achieved in moderate yields. To improve the yields, we examined alkylation of 2-alkoxy-2-phenylthioacetate 34 with allyl bromide 36 followed by an intamolecular glycosylation. Phenylthio-group serves as not only a stabilizer of an enolate in the alkylation but also a leaving group in the glycosylation. This method are underway in our laboratory.