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. 2010 May 7;12(9):1924-7.
doi: 10.1021/ol100467t.

Chemoselective protection of alpha-ketoacids by direct annulations with oximes

Melissa A Flores  1 , Jeffrey W Bode
Affiliations

Chemoselective protection of alpha-ketoacids by direct annulations with oximes

Melissa A Flores et al. Org Lett. .

Abstract

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.

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Figures

Scheme 1
Scheme 1
Annulations of oximes and α-ketoacids.a aAll reactions were preformed at 0.2 M CH2Cl2 for 12–16 h. Yields refer to mass yields of isolated, pure products. bReaction performed at 40 °C.
Scheme 2
Scheme 2
Chemoselective annulation, elaboration, and deprotection of α-ketoacids.
Scheme 3
Scheme 3
Stereoretentive protection of α-peptide ketoacids.
Scheme 4
Scheme 4
Stereoretentive protection of α-peptide ketoacids.
Scheme 5
Scheme 5
Postulated reaction pathways.
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