In this work, we implemented for the first time the cycloSaligenyl prodrug strategy to increase the bioavailability of fosmidomycin phosphate analogs in bacteria. Here, we report the synthesis of 34 cycloSaligenyl prodrugs of fosfoxacin and its derivatives. Among them, fifteen double prodrugs efficiently prevented the growth of the non-pathogenic, fast-growing Mycobacterium smegmatis.
Keywords: Mycobacterium smegmatis; cycloSaligenyl prodrug; deoxyxylulose 5-phosphate reducto-isomerase; fosfoxacin; isoprenoid biosynthesis.