N-Methylamino acids in peptide synthesis. VII. Studies on the enantiomeric purity of N-methylamino acids prepared by various procedures

1977 ◽  
Vol 55 (5) ◽  
pp. 916-921 ◽  
Author(s):  
S. T. Cheung ◽  
N. Leo Benoiton
Keyword(s):  
Amino Acid ◽  
Methyl Iodide ◽  
Peptide Synthesis ◽  
Liquid Ammonia ◽  
Silver Oxide ◽  
Sodium Hydride ◽  
Enantiomeric Purity ◽  
Amino Acid Analyzer ◽  
Pure Compounds ◽  
Optically Pure

The enantiomeric purity of N-methylamino acids and their derivatives obtained by various procedures has been examined by analysis with an amino-acid analyzer of the diastereomeric lysyl dipeptides formed by coupling them with a lysyl derivative. N-Benzyloxycarbonyl, and N-tert-butyloxycarbonyl,N-methylamino acids obtained by methylation of the parent derivative using sodium hydride and methyl iodide, and N-methylamino acids obtained by methylation of the p-toluenesulfonylamino acid followed by treatment with sodium in liquid ammonia, are optically pure. Compounds obtained by other procedures which include reductive alkylations or the use of silver oxide – methyl iodide are generally not optically pure.

N-Methylamino acids in peptide synthesis. V. The synthesis of N-tert-butyloxycarbonyl, N-methylamino acids by N-methylation

1977 ◽  
Vol 55 (5) ◽  
pp. 906-910 ◽  
Author(s):  
S. T. Cheung ◽  
N. Leo Benoiton
Keyword(s):  
Amino Acids ◽  
Amino Acid ◽  
Methyl Iodide ◽  
Peptide Synthesis ◽  
Room Temperature ◽  
Sodium Hydride ◽  
Amino Acid Derivatives ◽  
Enantiomerically Pure ◽  
Neutral Amino Acids ◽  
Related Data

The preparation of enantiomerically pure N-tert-butyloxycarbonyl,N-methylamino acids by N-methylation of the parent amino acid derivatives using sodium hydride and methyl iodide in tetrahydrofuran at room temperature is described for neutral amino acids including O-benzyl-protected threonine and tyrosine. Methylation of the O-benzylserine derivative under these conditions gives the N-methyldehydroalanine derivative. The β-elimination is completely suppressed, giving the corresponding N-methylserine derivative when the reaction is carried out at 5 °C. Other related data on N-methylation and N-methylamino acid derivatives are presented.

Synthesis of N-Methylamino Acid Derivatives from Amino Acid Derivatives using Sodium Hydride/Methyl Iodide

1971 ◽  
Vol 49 (11) ◽  
pp. 1968-1971 ◽  
Author(s):  
John R. Coggins ◽  
N. Leo Benoiton
Keyword(s):  
Amino Acid ◽  
Methyl Iodide ◽  
Methyl Esters ◽  
Acid Methyl Ester ◽  
Sodium Hydride ◽  
Amino Acid Derivative ◽  
Acid Methyl ◽  
High Yields ◽  
Optically Pure ◽  
Derivatives Of

Reaction of N-acetyl-, N-benzoyl-, and N-carbobenzoxy derivatives of aliphatic amino acids with sodium hydride/methyl iodide in tetrahydrofuran containing dimethylformamide at 80° gave the corresponding N-methylamino acid methyl esters as oils in high yields. Saponification of these gave the N-protected-N-methylamino acids, and decarbobenzoxylation gave the N-methylamino acid methyl ester hydrobomides. The products are essentially optically pure and free of unmethylated amino acid derivative.

HPLC Determination of Enantiomeric Purity of Protected Amino Acid Derivatives Used in Peptide Synthesis

1994 ◽  
Vol 17 (13) ◽  
pp. 2759-2775 ◽  
Author(s):  
Gy. Szókán ◽  
Sz. Hadfi ◽  
K. Krizsán ◽  
A. Liembeck ◽  
I. Krecz ◽  
...  
Keyword(s):  
Amino Acid ◽  
Peptide Synthesis ◽  
Enantiomeric Purity ◽  
Hplc Determination ◽  
Amino Acid Derivatives ◽  
Protected Amino Acid

Dimedone (5,5-Dimethylcyclohexane-1,3-dione) as a protecting agent for amino groups in peptide synthesis

1964 ◽  
Vol 17 (11) ◽  
pp. 1282 ◽  
Author(s):  
B Halpern ◽  
LB James
Keyword(s):  
Amino Acid ◽  
Peptide Synthesis ◽  
Amino Acid Esters ◽  
Protecting Group ◽  
Amino Groups ◽  
Active Esters ◽  
Optically Pure ◽  
Derivatives Of ◽  
Protected Peptides ◽  
Acid Esters

The reaction of dimedone (5,5-dimethylcyclohexane-1,3-dione) with amino-acid "active" esters leads to optically pure enamine derivatives. The dimedone derivatives of amino acid esters could also be converted by way of their hydrazides to the corresponding azides. The thiophenyl ester and azide derivatives have been used directly for peptide synthesis. The protecting group can easily be removed from the N-protected peptides by means of aqueous bromine, with the formation of 2,2-dibromodimedone and the hydrobromide of the corresponding peptide ester.

2-Alkoxy-5(4H)-oxazolones from N-alkoxycarbonylamino acids and their implication in carbodiimide-mediated reactions in peptide synthesis

1981 ◽  
Vol 59 (2) ◽  
pp. 384-389 ◽  
Author(s):  
N. Leo Benoiton ◽  
Francis M. F. Chen
Keyword(s):  
Amino Acid ◽  
Peptide Synthesis ◽  
Tertiary Amine ◽  
Acid Ester ◽  
Methyl Esters ◽  
Amino Acid Ester ◽  
Acid Methyl ◽  
Optically Pure ◽  
Amino Acid Methyl Esters

Reaction of N-ethyl,N′-(γ-dimethylaminopropyl)-carbodiimide- HCl with one equiv. of N-tert-butoxycarbonyl-L-valine (3a) in dichloromethane at 23 °C gives, besides the symmetrical anhydride (5a), the optically pure 2-tert-butoxy-4-isopropyl-5(4H)-oxazolone (4a) which can be obtained in 50% yield under selected conditions. The 2-benzyloxycarbonyl-4-isopropyl-5(4H)-oxazolone (4b) is similarly obtainable from N-benzyloxycarbonyl-L-valine (3b). Anhydrous acid converts 4a to the oxazolidinedione. Simple preparations of the N-carboxyanhydrides of valine and isoleucine have been devised from these reactions. Compound 4 reacts with 3 to give 5. Compound 4 reacts with an amino acid ester to give the optically pure peptide even in the presence of salts, but partial racemization occurs for reactions in the presence of a tertiary amine. Evidence for the implication of 2-alkoxy-5(4H)-oxazolones in the couplings of N-alkoxycarbonylamino acids is presented. Compound 4a has been isolated in 6–11% yield from carbodiimide-mediated reactions of 3a with itself or amino acid methyl esters which have been terminated before completion.

N-Methylamino acids in peptide synthesis. VI. A method for determining the enantiomeric purity of N-methylamino acids and their derivatives by ion-exchange chromatography as their C-terminal lysyl dipeptides

1977 ◽  
Vol 55 (5) ◽  
pp. 911-915 ◽  
Author(s):  
S. T. Cheung ◽  
N. Leo Benoiton
Keyword(s):  
Amino Acid ◽  
Ion Exchange ◽  
Nmr Spectra ◽  
Optical Purity ◽  
Ion Exchange Chromatography ◽  
Exchange Chromatography ◽  
Enantiomeric Purity ◽  
Protecting Groups ◽  
Configurational Assignment ◽  
Amino Acid Analyzer

A method capable of detecting one part in one thousand of the other isomer is described for determining the enantiomeric purity of N-methylamino acids and their cleavable derivatives. The method consists in converting the N-methylamino acid to its N-benzyloxycarbonyl derivative, and/or coupling the derivative with benzyl Nε-εbenzyloxycarbonyl-L-lysinate using N,N′-dicyclohexylcarbodiimide, followed by removal of protecting groups by catalytic hydrogenation or other cleavage methods not affecting the chirality of the product. The resulting diastereomeric lysyl peptides are analyzed by ion-exchange chromatography on a 15 cm column of Aminex A-5 resin using an amino-acid analyzer. The method is applicable to samples contaminated by the corresponding unmethylated amino acid or derivative, and in effect, provides a new method for determining the enantiomeric purity of amino acids and their derivatives as well.Examples are given where, in some cases, optical purity verification or configurational assignment for N-methylamino acids can be achieved by inspection of the nmr spectra of related lysyl dipeptide derivatives.

A Strategy for Thioamide Incorporation During Fmoc Solid-Phase Peptide Synthesis with Robust Stereochemical Integrity

2019 ◽  
Author(s):  
luis camacho III ◽  
Bryan J. Lampkin ◽  
Brett VanVeller
Keyword(s):  
Amino Acid ◽  
Functional Groups ◽  
Peptide Synthesis ◽  
Solid Phase ◽  
Solid Phase Peptide Synthesis ◽  
Side Chains ◽  
Amino Acid Side Chains ◽  
Peptide Elongation

We describe a method to protect the sensitive stereochemistry of the thioamide—in analogy to the protection of the functional groups of amino acid side chains—in order to preserve the thioamide moiety during peptide elongation.<br>

Series of sequential polypeptides containing lysine or arginine: Preparation and characterization

1988 ◽  
Vol 53 (1) ◽  
pp. 145-156 ◽  
Author(s):  
Jana Pírková ◽  
Svetlana Churkina ◽  
Vladimír Gut ◽  
Ivo Frič ◽  
Karel Bláha
Keyword(s):  
Molecular Weight ◽  
Amino Acid ◽  
Peptide Synthesis ◽  
Average Molecular Weight ◽  
Basic Amino Acid ◽  
Cd Spectra ◽  
Active Esters ◽  
Marked Tendency

The sequential polypeptides (Lys-Ala)n, (Lys-Ala-Ala)n, (Lys-Ala-Ala-Ala)n, (Lys-Leu-Ala)n, (Lys-Leu-Ala-Ala)n, (Lys-Leu-Ala-Ala-Ala)n, (Lys-Ala-Leu)n, (Lys-Ala-Leu-Ala)n, (Orn-Leu-Ala)n,(Arg-Ala-Ala)n, (Arg-Leu-Ala)n, (Arg-Leu-Ala-Ala)n, (Arg-Ala-Leu)n, and (Arg-Ala-Leu-Ala)n were synthesized by polymerization of active esters (1-succinimidyl or pentafluorophenyl) of the corresponding Nα-deblocked monomers. The monomers were prepared using the usual methods of peptide synthesis in solution. Upon dialysis, the average molecular weight of the polymer was 6 000-9 000 as determined by sedimentation in ultracentrifuge. Polypeptides, containing leucine in addition to the basic amino acid, showed a marked tendency to aggregation. CD spectra of the products were measured for characterization.

scholarly journals Altering the Stereoselectivity of Whole-Cell Biotransformations via the Physicochemical Parameters Impacting the Processes

Catalysts ◽  
2021 ◽  
Vol 11 (7) ◽  
pp. 781
Author(s):  
Agnieszka Raczyńska ◽  
Joanna Jadczyk ◽  
Małgorzata Brzezińska-Rodak
Keyword(s):  
Culture Conditions ◽  
Biologically Active ◽  
Enantiomerically Pure ◽  
Whole Cells ◽  
Chiral Compounds ◽  
Physicochemical Factors ◽  
Pure Compounds ◽  
Genetic Level ◽  
Prochiral Ketones ◽  
Optically Pure

The enantioselective synthesis of organic compounds is one of the great challenges in organic synthetic chemistry due to its importance for the acquisition of biologically active derivatives, e.g., pharmaceuticals, agrochemicals, and others. This is why biological systems are increasingly applied as tools for chiral compounds synthesis or modification. The use of whole cells of “wild-type” microorganisms is one possible approach, especially as some methods allow improving the conversion degrees and controlling the stereoselectivity of the reaction without the need to introduce changes at the genetic level. Simple manipulation of the culture conditions, the form of a biocatalyst, or the appropriate composition of the biotransformation medium makes it possible to obtain optically pure products in a cheap, safe, and environmentally friendly manner. This review contains selected examples of the influence of physicochemical factors on the stereochemistry of the biocatalytic preparation of enantiomerically pure compounds, which is undertaken through kinetically controlled separation of their racemic mixtures or reduction of prochiral ketones and has an effect on the final enantiomeric purity and enantioselectivity of the reaction.

Sign in / Sign up

Export Citation Format

Share Document