Structural variations of N ‐acetylneuraminic acid, 15. Synthesis of 9‐deoxy‐, 7,9‐dideoxy‐, and 4,7,9‐trideoxy‐ N ‐acetylneuraminic acid and their behaviour towards CMP‐sialate synthase

The methyl ester of N ‐acetylneuraminic acid β‐methyl ketoside (Neu5Ac1Me‐2β‐Me) ( 1 ) is used as common starting material for the synthesis of the title compounds. Combined derivatization reactions with reagents thiophosgene, p ‐cresol, benzoyl chloride, and acetic anhydride/pyridine lead to the thiocarbonate derivatives 2 , 6 – 8 , and 12 . Further transformation with iodomethane yields the 9‐iodo compounds 3, 9 , and 13 , which are reduced by tributyltin hydride to the deoxy derivatives 4 , 10 , and 14 . Hydrolysis of 14 , 10 , and 4 affords the desired 9‐deoxy, 7,9‐dideoxy‐, and 4,7,9‐trideoxy‐ N ‐acetylneuraminic acids 15 (9‐d‐Neu5Ac), 11 (7,9‐d 2 ‐Neu5Ac), and 5 (4,7,9‐d 3 ‐Neu5Ac), respectively. — The sialic acid analogues 11 and 5 were activated by CMP‐sialate synthase [E,C.2.7.7.43] to an extent of 30–40 and 50–60%, respectively, relative to N ‐acetylneuraminic acid.