The Synthesis of Hemiaminals as Potential Protease Inhibitors

Posted May 28th, 2010 at 12:09 pm.

Marisha Banerji
Mentor: Dr. William Malachowski

Hemiaminals are structures containing a carbon attached to a hydroxyl group and an amine. They have the same oxidation state as aldehydes, which have been proved to effectively inhibit proteases. In addition, they have the potential for extended binding interactions in the enzyme active site, leading to stronger and more specific inhibitors. Thus, hemiaminals can potentially inhibit serine proteases, which are enzymes that catalyze the hydrolysis of peptide bonds by a nucleophilic attack on the targeted bond by a serine.

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Nature of hemiaminals in solution

The focus of this summer's project is the synthesis of a key intermediate in the formation of a target hemiaminal. A synthesis was attempted to make the tri-flouroacetic acid salt of the methyl ester an amino acid (6). The synthesis was started with boc-ornithine being reacted with sodium hydroxide and hydrocinnamoyl chloride to make an amide (4). Compound (4) was then reacted with TMSCHN 2 to make a methyl ester (5), which was reacted with triflouroacetic acid CF 3 CO 2 H to make the salt, compound (6).

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Filed under: 2004,Banerji, Marisha,Malachowski, Dr. William by Ann Dixon

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