- Effective methods for the synthesis of N-methyl β-amino acids from all twenty common α-amino acids using 1,3-oxazolidin-5-ones and 1,3-oxazinan-6-ones
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N-Methyl β-amino acids are generally required for application in the synthesis of potentially bioactive modified peptides and other oligomers. Previous work highlighted the reductive cleavage of 1,3-oxazolidin-5-ones to synthesise N-methyl α-amino acids. Starting from α-amino acids, two approaches were used to prepare the corresponding N-methyl β-amino acids. First, α-amino acids were converted to N-methyl α-amino acids by the so-called '1,3-oxazolidin-5-one strategy', and these were then homologated by the Arndt-Eistert procedure to afford N-protected N-methyl β-amino acids derived from the 20 common α-amino acids. These compounds were prepared in yields of 23-57% (relative to N-methyl α-amino acid). In a second approach, twelve N-protected α-amino acids could be directly homologated by the Arndt-Eistert procedure, and the resulting β-amino acids were converted to the 1,3-oxazinan-6-ones in 30-45% yield. Finally, reductive cleavage afforded the desired N-methyl β-amino acids in 41-63% yield. One sterically congested β-amino acid, 3-methyl-3-aminobutanoic acid, did give a high yield (95%) of the 1,3-oxazinan-6-one (65), and subsequent reductive cleavage gave the corresponding AIBN-derived N-methyl β-amino acid 61 in 71% yield (Scheme 2). Thus, our protocols allow the ready preparation of all N-methyl β-amino acids derived from the 20 proteinogenic α-amino acids.
- Hughes, Andrew B.,Sleebs, Brad E.
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p. 2611 - 2637
(2007/10/03)
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- α-Oxymethyl ketone enolates for the asymmetric Mannich reaction. From acetylene and N-alkoxycarbonylimines to β-amino acids
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The insufficient diastereoselectivity and generality, which are the main problems of the 'acetate' aza - aldol reaction, can now be addressed through the reaction of the lithium enolate of endo-O-trimethylsilyl acetyl isoborneol with various N[(p-tolylsul
- Palomo, Claudio,Oiarbide, Mikel,Gonzalez-Rego, M. Concepcion,Sharma, Arun K.,Garcia, Jesus M.,Gonzalez, Alberto,Landa, Cristina,Linden, Anthony
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p. 1063 - 1066
(2007/10/03)
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