Synthesis of type 2 Lewis antigens via novel regioselective glycosylation of an orthogonally protected lactosamine diol derivative

•A facile and rapid synthesis of type 2 Lewis antigens is demonstrated.•A newly designed diol acceptor shows unique reactivity of 3-OH > 2′-OH.•On-demand synthesis of Lex and Ley is achieved with this new diol acceptor.•Synchronous synthesis of Lex and Ley is performed in this study for the first time. [Display omitted] The novel and efficient synthesis of type 2 Lewis antigens is reported in this study. The rationally designed lactosamine-3,2′-diol derivative with an orthogonal set of protecting groups is efficiently glycosylated with a benzyl protected 1-thio-l-fucoside donor in a unique regioselective manner to produce Lewis x (Lex) and Lewis y (Ley) derivatives in good yields. These derivatives can be prepared not only exclusively but also synchronously by choosing the appropriate reaction temperature and donor–acceptor molar ratio. The Lex derivatives are easily converted into sulfated or non-sulfated Lex bearing a terminal azido functionalized oligo-(ethyleneoxide) linker; the Ley derivative having the same linker can also be prepared, all of which can be further used for the chemical modification of other compounds and materials.