Enzymatic modular assembly of hybrid Lewis antigens

The enzymatic synthesis of hybrid Lewis antigens including KH-1 (Lewis y-Lewis x-Lactose, Le^y-Le^x-Lac), Lewis a-Lewis x-Lactose (Le^a-Le^x-Lac), and Lewis b-Lewis x-Lactose (Le^b-Le^x-Lac) has been achieved using a facile enzymatic modular assembly strategy. Starting from a readily available tetrasaccharide, 3 complex hybrid Lewis antigens were achieved in over 40% total yields in less than 5 linear steps of sequential enzymatic glycosylation using 6 enzyme modules. The regio-selective fucosylation was achieved by simply controlling the donor-acceptor ratio. This strategy provides an easy access to these biologically important complex hybrid Lewis antigens at preparative scales.