Optically pure N-hydroxy-O-triisopropylsilyl-alpha-L-amino acid methyl esters from AlCl3-assisted ring opening of chiral oxaziridines by nitrogen containing nucleophiles.
[reaction: see text] This article reports a straightforward and unprecedented process of AlCl3-assisted oxaziridine ring opening by nitrogen containing nucleophiles, in a totally anhydrous milieu. Under these conditions, nucleophiles exclusively attack the carbon atom of the three-membered heterocycles, obtained from methyl esters of natural alpha-amino acids, generating N-hydroxy-alpha-L-amino acid methyl esters. No nitrones, amides, or other side products, either from unwanted rearrangements or due to the attack of the nucleophile on the N atom of the oxaziridine systems, are formed. The hydroxylamine compounds are recovered in excellent yields, after their site-specific conversion into the corresponding O-triisopropylsilyl derivatives, by exposure to triisopropylsilyl triflate in the presence of 1H-imidazole. Derivatization, performed immediately after the recovery of the N-hydroxylated precursors, allows the chiral integrity of the asymmetric alpha-carbon atoms in the amino acid methyl esters to be retained. It also protects the obtained compounds from frame degradation by disproportionation. N-Hydroxy-O-triisopropylsilyl-alpha-L-amino acid methyl esters are important intermediates in the study of natural alpha-L-amino acid metabolic pathways and are ideal candidates as starting materials in the synthesis of biologically, pharmacologically, and nutritionally important N-hydroxy peptides.
Di Gioia
Maria Luisa
ML
Dipartimento di Scienze Farmaceutiche, Università della Calabria, Via P. Bucci, I-87036 Arcavacata di Rende (CS), Italy.
Leggio
Antonella
A
Le Pera
Adolfo
A
Liguori
Angelo
A
Siciliano
Carlo
C
D000596:Amino Acids / Q000138:chemical synthesis*; D001388:Aziridines / Q000737:chemistry; D004952:Esters / Q000138:chemical synthesis*; D009584:Nitrogen / Q000737:chemistry; D010078:Oxazines / Q000737:chemistry; D013237:Stereoisomerism
D000596:Amino Acids; D001388:Aziridines; D004952:Esters; D010078:Oxazines; D009584:Nitrogen