Reactivity–Stereoselectivity Mapping for the Assembly of Mycobacterium marinum Lipooligosaccharides

The assembly of complex bacterial glycans presenting rare structural motifs and cis‐glycosidic linkages is significantly obstructed by the lack of knowledge of the reactivity of the constituting building blocks and the stereoselectivity of the reactions in which they partake. We here report a strategy to map the reactivity of carbohydrate building blocks and apply it to understand the reactivity of the bacterial sugar, caryophyllose, a rare C12‐monosaccharide, containing a characteristic tetrasubstituted stereocenter. We mapped reactivity–stereoselectivity relationships for caryophyllose donor and acceptor glycosides by a systematic series of glycosylations in combination with the detection and characterization of different reactive intermediates using experimental and computational techniques. The insights garnered from these studies enabled the rational design of building blocks with the required properties to assemble mycobacterial lipooligosaccharide fragments of M. marinum.