Process for Synthesis of VBP15 as a Treatment for Duchenne Muscular Dystrophy

This technology includes processes for the synthesis of VBP15 (17a,21-dihydroxy-16a-methyl-pregna-1,4,9(11)-triene-3,20-dione) of high purity and large quantities as a treatment for Duchenne muscular dystrophy. The synthesis of VBP15 has several deficiencies which has hindered larger-scale preparation for clinical evaluation and potential manufacturing. The deficiencies included formation of significant levels of undesired epoxide impurity, formation of undesired ketone impurity, and resultant need for costly chromatographic purification. This new method relies on oxidizing agent (peracetic acid) that is typically not used for similar substrates (MCPBA is usually utilized), allows oxidation under milder conditions, and generates lower levels of epoxide impurity. The method also uses treatment with hydrogen bromide in a biphasic aqueous-organic solvent system to selectively decompose epoxide impurity to easily removable by-products.