Chemoselective protection of alpha-ketoacids by direct annulations with oximes.

Roy and Diana Vagelos Laboratories, Department of Chemistry, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.

Organic letters 2010 May 7

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Oximes and alpha-ketoacids undergo an unexpectedly facile and chemoselective annulation to afford 2,5-dihydrooxazole 3-oxides. The resulting cyclic nitrones serve as chemically and configurationally stable masked alpha-ketoacids that can be easily elaborated and manipulated. Deprotection is achieved by mild reduction with zinc metal and hydrolysis. This methodology allows for the protection, elaboration, and deprotection of enantiopure peptide derived alpha-ketoacids, which are the key starting materials for the chemoselective ketoacid-hydroxylamine peptide ligation.

Citation

Melissa A Flores, Jeffrey W Bode. Chemoselective protection of alpha-ketoacids by direct annulations with oximes. Organic letters. 2010 May 7;12(9):1924-7