Removal of glucose by a glycosidase, which is concomitant with export, weaponizes the macrolide. Sugar residues on erythromycin, another macrolide inhibitor of translation, can be beneficial or detrimental to its antibiotic activity, depending on the context. The cladinose sugar of erythromycin acts as a handle used by the efflux pumps that confer macrolide resistance to bacteria. Efflux out of the bacterial cytoplasm prevents association with the ribosome, and therefore a loss of activity. In fact, so called third generation macrolides like telithromycin lack the cladinose residue by design so that the compound is a poor substrate for efflux. Methymycin, erythromycin, and telithromycin all contain a desosamine sugar. Desosamine makes contacts with the RNA near the ribosomal exit tunnel that are essential to its activity. Specifically, there is a H-bond between its C2 hydroxyl and the N1 of adenine 2058 (E. coli) in the ribosome and an electrostatic interaction between the protonated C3 dimethylamino group and a nearby phosphate. These macrolide examples additionally underscore the importance of amino sugars in particular as mediators of small molecule bioactivity, especially in the context of small moleculenucleic acid interactions. The advantages of incorporating carbohydrates onto lead molecules are attractive for the development of new drug candidates. A traditional approach toward the synthesis of families of glycosylated small molecules follows a "diversify then glycosylate" strategy. In such a scenario, an aglycone library is synthesized and parallel glycosylations are conducted afterward to complete the library assembly. The glycosylation reactions used to prepare library compounds, however, are notorious for being temperamental. More precisely, each new substrate can require slightly different reaction conditions and reagents that need to be optimized to affect reaction. Moreover, the glycosylations can give rise to anomeric mixtures that are difficult to separate by chromatography. These drawbacks make the preparation of libraries through parallel glycosylation daunting. Recent methods, specifically glycorandomization and neoglycorandomization, represent the cutting edge of glycosylated small molecule library synthesis. Enzymes from glycosylated natural product biosynthetic clusters are mixed and matched, or mutated to relax substrate specificity in the glycorandomization approach.