Synthesis of Hydroxylamines as Indoleamine-2, 3-dioxygenase Inhibitors

Posted July 26th, 2011 at 5:08 pm.

Abstract: Maisha Rahman

Mentor: William Malachowski

Indoleamine-2, 3-dioxygenase (IDO) is an enzyme which has been found in high levels in cancer patients and linked to a decline in T cells. Research suggests that inhibiting the function of this enzyme could improve the effectiveness of chemotherapy by promoting a more robust immune response to the developing tumor.

Hydroxylamines have been found to be inhibitors of IDO; specifically, compounds containing phenyl rings with electron withdrawing groups seem to be the most effective. My summer research project is to prepare a series of hydroxylamine compounds with various substituents. This is to be done via the Mitsunobu reaction, which involves the substitution of primary and secondary alcohols with a nucleophile in the presence of triphenylphosphine and diisopropyl azodicarboxylate. In a second step, hydrazine monohydrate is added in order to reveal the critical hydroxylamine moiety. The product is then recrystallized as an HCl salt to obtain an extremely pure sample for testing on isolated IDO by our biological collaborators.

Filed under: 2011,Malachowski, Dr. William,Rahman, Maisha by Michelle Han

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