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

✍ Scribed by Roth, Andreas ;Faillard, Hans

• Publisher: John Wiley and Sons
• Year: 1993
• Tongue: English
• Weight: 622 KB
• Volume: 1993
• Category: Article
• ISSN: 0947-3440
• DOI: 10.1002/jlac.199319930180

✦ Synopsis

Abstract

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]‐Neu5,7,8,9Ac~4~} (3) and 2α‐[4‐(dansylamino)phenylthio]‐4‐O‐acetyl‐N‐acetylneuraminic acid {2α‐[4‐(dansylamino)phenylthio]‐Neu4,5Ac~2~} (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 Zemplén 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]‐Neu4,5Ac~2~ (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.