Total Synthesis of Kanamycins

Structurally modified aminoglycosides, such as kanamycin, have shown promise as antibiotics and premature termination codon read-through drugs to fight against drug-resistant bacteria and to treat genetic diseases, respectively. Therefore, research on developing and discovering aminoglycoside antibiotics has recently increased. However, synthetic strategies for controllably positioning the two 1,2-cis-glycoside moieties on the symmetrical structure of kanamycin have not yet been established. Herein, we report on a novel route for the total synthesis of kanamycins A and B via regio- and stereoselective introduction of 1,2-cis-glycosidic linkages as the key step. We successfully synthesized α(1,6)-linked glycoside using a 1,2-anhydro donor and 2-deoxy-myo-inositol 1,3,5-orthoformate acceptor in the presence of a boronic acid catalyst via desymmetric boron-mediated aglycon delivery. In addition, we also synthesized α(1,4)-linked glycoside using its corresponding trichloroacetimidate donor.