Nanomole-Scale Assignment of Configuration for Primary Amines Using a Kinetic Resolution Strategy

Miller, Shawn M.; Samame, Renzo Alexander; Rychnovsky, Scott D.

doi:10.1021/ja310620c

Cited by 21 publications

(17 citation statements)

References 28 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Chemical derivatization, especially using probes with isotope labeling, has been proven to be an efficient approach for the identification of small chiral molecules in complicated matrixes. − Herein, a pair of mass-tagged chiral benzylicaldehyde probes, 1-(S)- 1 H and 2-(R)- 2 D, was designed for determining the absolute configuration of amino acid residues in peptides, with several structural features shown in Figure . The rationale for the design of these two probes is as follows.…”

mentioning

confidence: 99%

Pair of Stereodynamic Chiral Benzylicaldehyde Probes for Determination of Absolute Configuration of Amino Acid Residues in Peptides by Mass Spectrometry

et al. 2017

View full text Add to dashboard Cite

This paper describes a simple method to determine the absolute configuration of amino acids residues in peptides by mass spectrometry using a newly developed pair of mass-tagged chiral probes without the requirement of reference standards. A pair of benzylicaldehyde probes, 1-(S)-H in S configuration and 2-(R)-D in deuterium-labeled R configuration with the ratio of 1:1, were synthesized for in situ condensation with amino acid residues and transformed into a pair of stereodynamic imine products. The characteristic intensity difference observed in mass spectrometry can be used to determine the absolute configuration and to quantify the enantiomeric composition of chiral amino acid residues. Significant chiral recognition ability was achieved for 18 natural chiral amino acids and for one β-amino acid by comparing the ion intensity ratio of imine products I to I. For 16 kinds of amino acids, the L form of the amino acids was more reactive with 1-(S)-H, while D configuration amino acids preferred to react with 2-(R)-D. However, for three kinds of amino acid, the opposite result was obtained. The configurations of the residues in the peptides, Phe-Tyr-Ala, D-Phe-Tyr-Ala, Val-Pro-Phe-D-Leu-Met, Val-Pro-Phe-Leu-D-Met, as well as in a natural peptide with unknown chirality were determined by acid hydrolysis followed by the present method. In addition, molecular modeling results illustrate that the recognition process is mainly controlled by kinetic factors. Using the new probes coupled with a mass spectrometry approach avoids time-consuming workup and separation steps. We expect that the probes could be applied as tools to determine the absolute configuration of amino acid residues in proteins in future research.

show abstract

mentioning

confidence: 99%

Pair of Stereodynamic Chiral Benzylicaldehyde Probes for Determination of Absolute Configuration of Amino Acid Residues in Peptides by Mass Spectrometry

et al. 2017

View full text Add to dashboard Cite

show abstract

“…18–20 A mnemonic then confirms the absolute configuration based on the fast reacting enantiomer of the kinetic resolution reagent. The method is a modern implementation of the Horeau method.…”

mentioning

confidence: 72%

“…A similar strategy was developed for primary amines where the parallel reactions of proto and deutero chiral acylating reagents were analyzed by mass spectrometry. 20 …”

mentioning

confidence: 99%

Determination of Absolute Configuration of Secondary Alcohols Using Thin-Layer Chromatography

Wagner

Rychnovsky

2013

J. Org. Chem.

Self Cite

View full text Add to dashboard Cite

A new implementation of the Competing Enantioselective Conversion (CEC) method was developed to qualitatively determine the absolute configuration of enantioenriched secondary alcohols using thin-layer chromatography. The entire process for the method requires approximately 60 min and utilizes micromole quantities of the secondary alcohol being tested. A number of synthetically relevant secondary alcohols are presented. Additionally, 1H NMR spectroscopy was conducted on all samples to provide evidence of reaction conversion that supports the qualitative method presented herein.

show abstract

“…The CEC method has been applied to determine the absolute configuration of secondary alcohols, 8 lactams, 9 oxazolidinones, 9 primary amines, 10 and amino acid derivatives 11 by using Birman's HBTM acylation catalysts, 8a,b,9 DMAP catalysts,8c Mioskowski's acylating reagent 10 and molecularly imprinted polymers of DuoMIPs. The relative reaction rates of an optically pure substrate with an enantiomeric pair of catalysts are measured by 1 H NMR and the difference between the two reactions identifies the fast-reacting catalyst.…”

Section: Introductionmentioning

confidence: 99%

The assignment of the configuration for α-hydroxy acid esters using a CEC strategy

et al. 2016

View full text Add to dashboard Cite

A simple and efficient (1)H NMR method for determining the absolute configuration of chiral α-hydroxy acid esters using a competing enantioselective conversion (CEC) strategy was developed. The α-hydroxy acid esters were acylated in the presence of Feng's chiral N,N'-dioxide-scandium(iii) complex, and the faster reaction was identified when one enantiomer of the chiral α-hydroxy acid ester was treated with both enantiomers of the ligand by NMR analysis of the reaction mixture without further purification. A mnemonic is presented to aid the assignment of the absolute configuration of the substrates.

show abstract

Nanomole-Scale Assignment of Configuration for Primary Amines Using a Kinetic Resolution Strategy

Cited by 21 publications

References 28 publications

Pair of Stereodynamic Chiral Benzylicaldehyde Probes for Determination of Absolute Configuration of Amino Acid Residues in Peptides by Mass Spectrometry

Pair of Stereodynamic Chiral Benzylicaldehyde Probes for Determination of Absolute Configuration of Amino Acid Residues in Peptides by Mass Spectrometry

Determination of Absolute Configuration of Secondary Alcohols Using Thin-Layer Chromatography

The assignment of the configuration for α-hydroxy acid esters using a CEC strategy

Contact Info

Product

Resources

About