Improved α‑Sialylation through the Synergy of 5‑N,4‑O‑Oxazolidinone Protection and Exocyclic C‑1 Neighboring Group Participation
journal contributionposted on 01.07.2021, 18:12 by Yongliang Zhang, Min Yang, Xiaolei Wang, Guofeng Gu, Feng Cai
Stereoselective construction of α-sialyl linkages is one of the most significant challenges in carbohydrate chemistry. In this research, we developed a novel strategy for stereoselective synthesis of α-linked sialosides by protecting the 5-N,4-O-positions of a sialyl donor with an oxazolidinone group and its C-1 carboxylic functionality with a cyanoethyl ester to promote α-glycosylation. We also adopted the more electrophilic N-bromosuccinimide as a promoter to readily activate p-tolyl thiosialoside at −78 °C. The sialylation using this sialyl donor gave excellent yields and α-selectivity. The new synthetic method was used to successfully construct naturally occurring α-sialosides having sialic acid linked to the 6-O- or 3-O-position of galactoside, or 8-O-position of another sialic acid, respectively, as well as other α-linked sialosides.