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

Publisher Website
Google Scholar
Abstract
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‐d2‐Neu5Ac), and 5 (4,7,9‐d3‐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.

This publication has 21 references indexed in Scilit: