A convenient synthesis of the side chain of loteprednol etabonate—An ocular soft corticosteroid from 20-oxopregnanes using metal-mediated halogenation as a key reaction

A facile synthesis of the side chain of loteprednol etabonate, namely, chloromethyl-17α-[(ethoxycarbonyl))oxy]-11β-hydro of loteprednol etabonate, viz., chloromethyl-17α-[(ethoxycarbonyl))oxy]-11xy-3-oxoandrosta-1,4-diene-17β-carboxylate – an ocular soft corticosteroid, has been described starting from a 20-oxopregnane, namely, 3β-acetoxy-pregn-5(6),16(17)-diene-20-one (16-dehydropregnenolone acetate, i.e., 16-DPA) using our recently developed metal-mediated halogenation as a key reaction.

Figure optionsDownload as PowerPoint slideResearch highlights
► We develop a facile synthesis of the side chain of loteprednol etabonate – a potential ocular soft corticosteroid.
► In the method our newly introduced metal mediated halogenation using MnO2–TMSCl/AcCl–AcOH system has been used as a key reaction in C-21 functionalization of the starting compound, viz., 20-oxopregnane derivative.
► This metal mediated key reaction effecting C-21 functionalization of the 20-oxopregnane helped in achieving the synthesis of the side chain of Loteprednol etabonate in much easier way than those of the existing methods.