A New Synthesis of Chiral Oxazolidinones from the Amino Acid L-serine

Title:A New Synthesis of Chiral Oxazolidinones from the Amino Acid L-serine

Volume: 10 Issue: 9

Author(s): Thais C.M. Nogueira, Alessandra C. Pinheiro, Carlos R. Kaiser, James L. Wardell, Solange M.S.V. Wardell and Marcus V.N. de Souza

Affiliation:

Keywords: L-serine, N-Boc group, N-Cbz group, oxazolidinones, tuberculosis, X-ray crystallography.

Abstract: Cyclization of the (4S)-PhCH₂OCONHCH(CH₂OH)CONHN=CH-aryl, obtained in 4 steps from L-serine, on treatment with MeI and potassium carbonate, generates the chiral oxazolidinones, (4S)-N'-[(E)-(phenyl)methylidene]-Nmethyl- 2-oxo-1,3-oxazolidine-4-carbohydrazides. Overall the formation of the (4S)-N'-[(E)-(phenyl)methylidene]-Nmethyl- 2-oxo-1,3-oxazolidine-4-carbohydrazides from L-serine occurs with retention of configuration, as confirmed by Xray crystallography. In contrast, the reaction of the N-Boc analogues, (4S)-t-BuOCONHCH(CH₂OH)CONHN=CH-aryl, on treatment with MeI / K₂CO₃, simply leads to N-methylation without cyclization and without loss of the Boc protecting group to give (4S)-t-BuOCONMeCH(CH₂OH)CONHN=CH-aryl. The difference between the Boc and Cbz derivatives is striking and is probably linked to the greater bulk of the Boc group blocking the intramolecular acyl transfer.

Cite this article as:

Nogueira C.M. Thais, Pinheiro C. Alessandra, Kaiser R. Carlos, Wardell L. James, Wardell M.S.V. Solange and de Souza V.N. Marcus, A New Synthesis of Chiral Oxazolidinones from the Amino Acid L-serine, Letters in Organic Chemistry 2013; 10 (9) . https://dx.doi.org/10.2174/15701786113109990028