An alternative synthesis for Exatecan mesylate

Abstract

An alternative approach for the synthesis of Exatecan mesylate is described. A 7-step synthetic route has been developed to prepare Exatecan from compound 5. The first step of iodination reaction has better selectivity efficiently avoiding undesirable positional isomers. Simultaneous reduction in one step after the introduction of nitro, olefin and nitroso avoids excessive step-by-step reduction. The cyclics (9) was successfully synthesized by intramolecular Friedel-Crafts acylation of tert-butyl esters with indium trichloride. By utilizing the epimerization in deacetylation reaction, exaltecan was recovered from the mother liquor, and the total yield of this synthesis route reached 12 %.