Total Synthesis of Kasugamycin

Abstract

We present an efficient synthetic pathway for kasugamycin, an aminoglycoside antibiotic, utilizing naturally derived carbohydrates as starting materials. This synthesis effectively addresses stereochemical complexities by employing the selective reduction of d-fucal, which generates a crucial 3-deoxyglycal intermediate. This intermediate facilitates the introduction of amino groups at the C-2 and C-4 positions, which is essential for the synthesis of kasugamine. Subsequent glycosylation with glycosyl 1-O-m-chlorobenzoate (mCBz) donors yields a disaccharide intermediate, which is further transformed to produce kasugamycin. This streamlined approach provides a practical and effective route for the synthesis of kasugamycin and related deoxy amino sugar-containing antibiotics.