Design, Synthesis and X-ray Crystal Structure of Iodinated Benzoboroxole Derivatives by Consecutive Metal-Iodine Exchange of 3,4,5-Triiodoanisole

A series of iodinated benzoboroxoles was designed and synthesized by using a successive metal-iodine exchange reaction of 3,4,5-triiodoanisole. The reactivity and regioselectivity of the metal-iodine exchange are remarkably controlled and provide the iodinated products in good yields. The synthesized iodobenzoboroxoles were screened for in vitro antimicrobial activity against two Gram-positive strains of bacteria, Micrococcus luteus (ATCC 9341) and Bacillus cereus (ATCC 11778), and two Gram-negative strains, Escherichia coli (ATCC 25922) and Serratia marcescens (ATCC 27117), by using a well-diffusion assay and dilution methods. The in vitro antimicrobial evaluation indicated that 4-iodo-6-methoxybenzo[c][1,2]oxaborol-1(3H)-ol (compound 24) possesses the most-potent antibacterial activity against Gram-positive strains with a minimum inhibitory concentration (MIC) of 0.016 and 0.013 mg/mL for Micrococcus luteus and Bacillus cereus, respectively. This report discloses a two-step protocol for the synthesis of hitherto unknown 4-iodobenzoboroxole and 7-iodobenzoboroxole derivatives that is efficient, general in scope and scalable.