Amino Acids

, Volume 43, Issue 4, pp 1643–1652 | Cite as

High yielding synthesis of N-ethyl dehydroamino acids

Original Article

Abstract

Recently we reported the use of a sequence of alkylation and dehydration methodologies to obtain N-ethyl-α, β-dehydroamino acid derivatives. The application of this N-alkylation procedure to several methyl esters of β,β-dibromo and β-bromo, β-substituted dehydroamino acids protected with standard amine protecting groups was subsequently reported. The corresponding N-ethyl, β-bromo dehydroamino acid derivatives were obtained in fair to high yields and some were used as substrates in Suzuki cross-coupling reactions to give N-ethyl, β,β-disubstituted dehydroalanine derivatives. Herein, we further explore N-ethylation of β-halo dehydroamino acid derivatives using triethyloxonium tetrafluoroborate as alkylating agent, but substituting N,N-diisopropylethylamine for potassium tert-butoxide as auxiliary base. In these conditions, for all β-halo dehydroamino acid derivatives, reactions were complete and the N-ethylated derivative could be isolated in high yield. This method was also applied for N-ethylation of non-halogenated dehydroamino acids. Again, with all compounds the reactions were complete and the N-ethyl dehydroamino acid derivatives could be isolated in high yields. Some of these N-ethyl dehydroamino acid methyl ester derivatives were converted in high yields to their corresponding acids and coupled to an amino acid methyl ester to give N-ethyl dehydrodipeptide derivatives in good yields. Thus, this method constitutes a general procedure for high yielding synthesis of N-ethylated dehydroamino acids, which can be further applied in peptide synthesis.

Keywords

Amino acids Nonnatural amino acids Alkylation N-ethyl dehydroamino acids Protecting groups 

Notes

Acknowledgments

Foundation for Science and Technology (FCT)—Portugal and Fundo Europeu de Desenvolvimento Regional (FEDER) for financial support to Chemistry Centre of University of Minho. The NMR spectrometer Bruker Avance II+ 400 is part of the National NMR Network and was purchased in the framework of the National Program for Scientific Re-equipment; contract REDE/1517/RMN/2005, with funds from POCI 2010, FEDER and FCT.

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Copyright information

© Springer-Verlag 2012

Authors and Affiliations

  1. 1.Chemistry CentreUniversity of MinhoGualtarPortugal

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