Charla Ramsey (Ricerca)
John McCall (ReveraGen BioPharma Inc.)
Marco Burello (Ricerca Biosciences, LLC)
Mark Behnke (NCATS)
This technology includes processes for the synthesis of VBP15 (17α,21-dihydroxy-16α-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.
The method allows manufacture of clinical and commercial quantities of VBP15, which is being investigated as a potential treatment for Duchenne muscular dystrophy.
- Avoids use of costly extensive chromatographic purification
- Allows preparation of VBP15 with purity level acceptable for clinical use, including epoxide content below limit of detection of typical HPLC analytical method.