Efficient synthesis of α-galactosylceramide and its C-6 modified analogs

Huiting Li; Hongzhao Mao; Chao Chen; Ying Xu; Shuai Meng; Tiantian Sun; Chengli Zong

doi:10.3389/fchem.2022.1039731

Efficient synthesis of α-galactosylceramide and its C-6 modified analogs

Front Chem. 2022 Nov 25:10:1039731. doi: 10.3389/fchem.2022.1039731. eCollection 2022.

Authors

Huiting Li¹, Hongzhao Mao¹, Chao Chen², Ying Xu¹, Shuai Meng¹, Tiantian Sun¹, Chengli Zong¹

Affiliations

¹ Key Laboratory of Tropical Biological Resources of Ministry of Education, School of Pharmaceutical Sciences, College of Marine Science, Hainan University, Haikou, China.
² Anyikang Co., LTD., Shanghai, China.

Abstract

The synthesis of α-galactosylceramide (KRN7000) and its C-6 modified analogs remains a challenge due to the difficult α-1,2-cis-glycosidic bond. A non-participating benzyl (Bn) protecting group has been commonly used to favor the α-glycosylation product. Here, we report the α-selective glycosylation by using a bulky 4,6-O-di-tert-butylsilylene (DTBS) galactosyl donor, regardless of the 2-benzoyl (Bz) participating group. Compared with Bn, Bz groups can be selectively removed in basic conditions without impacting the C-6 azide modification. The azide has the potential for clicking with alkyne or being easily transformed to other functional groups.

Keywords: analogs; click chemistry; glycosylation; orthogonal protection strategy; α-galactosylceramide.