An Efficient Synthesis of<i>N</i>-Methyl Amino Acids by Way of Intermediate 5-Oxazolidinones

Aurelio, Luigi; Box, John S.; Brownlee, Robert T. C.; Hughes, and Andrew B.; Sleebs, Marianne M.

doi:10.1021/jo026722l

Cited by 106 publications

(60 citation statements)

References 40 publications

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“…[18] (27) and (S)-2-(methylamino)-2-phenylethanol (36) are commercially available. Ethyl (S)-1-methylpyrrolidine-2-carboxylate (10) was obtained in three steps from -proline by N-methylation using formaldehyde, followed by catalytic hydrogenation (99 % yield) [19] and esterification (EtOH, cat. SOCl 2 ) (90 % yield).…”

Section: Resultsmentioning

confidence: 99%

An Approach to Enantioselective 5‐endo Halo‐Lactonization Reactions

2007

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Enantioselective lactonization of 4‐substituted but‐3‐enoic acids using iodobis(N‐methylephedrine) hexafluoroantimonate in dichloromethane at low temperatures is reported. The presence of bis(N‐methylephedrine)silver(I) hexafluoroantimonate, derived from the excess amounts of N‐methylephedrine and silver hexafluoroantimonate that were necessary for the generation of the iodo complex in the reaction mixture, is crucial for the success of this reaction. The different parameters of these cyclization reactions have been examined. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2007)

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Section: Resultsmentioning

confidence: 99%

An Approach to Enantioselective 5‐endo Halo‐Lactonization Reactions

2007

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“…The l-amino acids were dissolved in aqueous NaOH at 0°C and an ethereal solution of p-toluenesulfonyl chloride was added dropwise while stirring over several hours to give the tosyl amino acids 1c and 2b. Following the reported method, [12] l-proline in methanol was allowed to react with a solution of 40 % aqueous formaldehyde and then reduced with hydrogen catalyzed by Pd/ C. This produced N-methylproline (1d) in high yield (Scheme 2). The ligand 1e was readily prepared by adding benzoyl chloride to a solution of l-proline in 2.0 m NaOH (Scheme 3).…”

Section: Resultsmentioning

confidence: 99%

Simple Derivatives of Natural Amino Acids as Chiral Ligands in the Catalytic Asymmetric Addition of Phenylacetylene to Aldehydes

et al. 2005

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Optically active propargylic alcohols are important chiral building blocks in asymmetric synthesis, and asymmetric addition of terminal alkynes to aldehydes is one of the most important and interesting procedures by which to prepare these chiral building blocks. In this work we have identified some simple derivatives of (S)-proline and other natural amino acids as chiral ligands that can be combined with

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“…Relatively few N-Fmoc-N-methyl amino acids are commercially available and ready for the peptide-coupling reaction: these include Fmoc-NMe-Val-OH, Fmoc-NMe-Phe-OH, Fmoc-NMe-Ala-OH, Fmoc-NMe-Leu-OH, Fmoc-NMe-Ile-OH, and Fmoc-NMe-Met-OH. These compounds were readily synthesized by the general method of Aurelio et al (47) and incorporated into the peptide using standard HBTU-mediated peptide coupling chemistry. When N-methylation of other residues was required the "on-resin" method of Miller and Scanlan (25) was used.…”

Section: Synthesis Of N-methylated R1mentioning

confidence: 99%

Rapid Optimization of a Peptide Inhibitor of Malaria Parasite Invasion by Comprehensive N-Methyl Scanning

Harris

Casey

Coley

et al. 2009

Journal of Biological Chemistry

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Apical membrane antigen 1 (AMA1) of the malaria parasite Plasmodium falciparum has been implicated in the invasion of host erythrocytes and is an important vaccine candidate. We have previously described a 20-residue peptide, R1, that binds to AMA1 and subsequently blocks parasite invasion. Because this peptide appears to target a site critical for AMA1 function, it represents an important lead compound for anti-malarial drug development. However, the effectiveness of this peptide inhibitor was limited to a subset of parasite isolates, indicating a requirement for broader strain specificity. Furthermore, a barrier to the utility of any peptide as a potential therapeutic is its susceptibility to rapid proteolytic degradation. In this study, we sought to improve the proteolytic stability and AMA1 binding properties of the R1 peptide by systematic methylation of backbone amides (N-methylation). The inclusion of a single N-methyl group in the R1 peptide backbone dramatically increased AMA1 affinity, bioactivity, and proteolytic stability without introducing global structural alterations. In addition, N-methylation of multiple R1 residues further improved these properties. Therefore, we have shown that modifications to a biologically active peptide can dramatically enhance activity. This approach could be applied to many lead peptides or peptide therapeutics to simultaneously optimize a number of parameters.

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An Efficient Synthesis ofN-Methyl Amino Acids by Way of Intermediate 5-Oxazolidinones

Cited by 106 publications

References 40 publications

An Approach to Enantioselective 5‐endo Halo‐Lactonization Reactions

An Approach to Enantioselective 5‐endo Halo‐Lactonization Reactions

Simple Derivatives of Natural Amino Acids as Chiral Ligands in the Catalytic Asymmetric Addition of Phenylacetylene to Aldehydes

Rapid Optimization of a Peptide Inhibitor of Malaria Parasite Invasion by Comprehensive N-Methyl Scanning

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