Synthesis of Fluorescent 7,8,9-Tri-O-acetyl-N-acetyl- and 4-O-Acetyl-N-acetylneuraminic Acid α-Thioketosides

Two new fluorescent regioselective O-acetylated N-acetylneuraminic acid (Neu5Ac) thioketosides, 2α-[4-(dansylamino)phenylthio]-7,8,9-tri-O-acetyl-N-acetylneuraminic acid {2α-[4-(dansylamino)phenylthio]-Neu5,7,8,9Ac4} (3) and 2α-[4-(dansylamino)phenylthio]-4-O-acetyl-N-acetylneuraminic acid {2α-[4-(dansylamino)phenylthio]-Neu4,5Ac2} (9) were synthesized. The synthesis of both derivatives started with the peracetylated benzyl ester 1 as precursor. The 7,8,9-tri-O-acetylated compound was prepared by partial deacetylation of 1 with sodium methoxide or with hydrazine hydrate, followed by catalytic benzyl ester hydrogenolysis. – Complete Zemplen deacetylation of 1 gave the Neu5Ac benzyl ester thioketoside 4, which was converted into the 8,9-isopropylidene-protected compound 5. By carefully performed regioselective 4-O-acetylation with acetic anhydride/pyridine in dichloromethane we obtained the desired fluorescent 4-O-acetyl derivative 6 and the nonfluorescent sulfonacetamide 7 as byproduct. Acidic 8,9-deprotection of 6 and finally catalytic hydrogenolysis of the benzyl ester 7 terminated this synthetic route, yielding 2α-[4-(dansylamino)phenylthio]-Neu4,5Ac2 (9). – The 4-O-acetylated derivative 9 could not be de-O-acetylated by influenza-C virus esterase. However, the virus esterase transformed the tri-O-acetylated derivative 3 in small amounts into the Neu5Ac thioketoside 10.