208655-75-8

Upstream product

• 60027-61-4 methyl (2Z)-2-(N-benzyloxycarbonylamino)but-2-enoate 

Downstream Products

• 1353643-09-0 Z-N(Et)-Z-ΔAbu(β-C6H5)-OMe 
• 1353642-97-3 Z-N(Et)-Z-ΔAbu(β-Br)-OMe 

Relevant academic research and scientific papers

High yielding synthesis of N-ethyl dehydroamino acids

Recently we reported the use of Asequence 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 Ageneral procedure for high yielding synthesis of N-ethylated dehydroamino acids, which can be further applied in peptide synthesis.

Synthesis of new N-ethyl dehydroamino acid derivatives: N-ethyl β,β-dibromo, N-ethyl β-bromo β-substituted, and N-ethyl β,β-disubstituted N-protected dehydroamino acid methyl esters

Recently, we reported the use of a sequence of alkylation and dehydration methodologies to obtain new non-proteinogenic amino acids (N-ethyl α,β-dehydroamino acids) from the methyl esters of N-(4-nitrophenylsulfonyl) β-hydroxy amino acids. Thus, it was possible to obtain for the first time, non-natural amino acids that incorporate both N-ethyl and α,β-dehydro moieties. Herein, we report 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 such as tert-butyloxycarbonyl, benzyloxycarbonyl, and (4-nitrobenzyl)oxycarbonyl, as well as acyl and sulfonyl groups. The procedure allows the synthesis of the methyl esters of N-protected N-ethyl β,β-dibromo and N-ethyl β-bromo β-substituted dehydroamino acids in fair to high yields. Some of these N-ethylated dehydroamino acid derivatives were used as substrates in cross-coupling reactions to give β,β-disubstituted N-ethyldehydroalanine derivatives. N-Ethylation of the methyl esters of β,β-dibromo and β-bromo, β-substituted dehydroamino acids protected with standard amine protecting groups is reported. The procedure allows the corresponding N-ethyl derivatives to be obtained in fair to high yields. These substrates can be applied in cross-coupling reactions, and constitute valuable synthons for the synthesis of N-ethyl derivatives. Copyright

Reactivity of dehydroamino acids and dehydrodipeptides towards N- bromosuccinimide: Synthesis of β-bromo- and β,β- dibromodehydroamino acid derivatives and of substituted 4-imidazolidinones

We have developed a modification of our previously reported high-yielding method for the synthesis of N,N-diacyldehydroamino acid derivatives to prepare N-monoprotected dehydroamino acids and dehydrodipeptides. Thus, several dehydroalanine, dehydroaminobutyric acid and dehydrophenylalanine derivatives have been prepared by treating the corresponding L-serine, L-threonine and D,L-3-phenylserine (threo-type) derivatives with 1 equiv. of di-tert-butyl dicarbonate and 4-(dimethylamino)pyridine. The reaction proceeded with the initial formation of an O-tert-butyl carbonate which, by treament with N,N,N′,N′-tetramethylguanidine, underwent β elimination to give the corresponding dehydroamino acid derivative. This two-step method can be carried out as a one-pot procedure and is stereoselective, giving only the Z isomer. The N-monoprotected dehydroamino acids were treated with N-bromosuccinimide and thereafter with triethylamine to afford several β,β-dibromodehydroalanines or β-bromo-, β-alkyl- or β-aryldehydroalanines. The latter were obtained as mixtures of E and Z isomers. An increased stereoselectivity towards the formation of the Z isomer was observed with dehydrophenylalanine and when 4-tolylsulfonyl was used as the N-protecting group. In the case of dehydrodipeptides, the reaction with NBS and triethylamine afforded the corresponding brominated dehydrodipeptides when the N-protecting group was other than 4-tolylsulfonyl. However, when the reagent was a peptide with a dehydroamino acid as the second residue and an N-(4-tolylsulfonyl) group the corresponding 2,2-disubstituted 1-(4-tolylsulfonyl)imidazolidin-4-ones were obtained in good-to-high yields. Wiley-VCH Verlag GmbH & Co. KGaA, 2007.