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 stereo‐selective 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.