Dylan Hoffman, “Synthesis of Glucuronic Acid Conjugate of MIDD0301”
Mentor: Alexander Arnold, Chemistry & Biochemistry

The testing of phase I and phase II metabolite of new drug candidates is warranted by the FDA for approval of first in man studies. One possible phase II metabolites of acid compounds are glucuronic acid conjugates. These metabolites that are formed in the liver by uridine 5′-diphospho-glucuronosyltransferases to increase the solubility of compounds and enable secretion. The Arnold group is currently developing an oral drug named MIDD0301 to treat asthma, which has an acid functionality. To explore how much of the glucuronic acid conjugate of MIDD0301 is formed in vivo, we are synthesizing this compound as analytical standard to enable quantification by LC-MS/MS. The synthesis of this conjugate requires two synthesis steps. This study describes the synthesis of one of the starting materials, which include the reaction of allyl bromide and glucuronic acid. The purification of this product has been challenging but is expected to give a yield of 60%.

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