Large-scale asymmetric synthesis of novel sterically constrained 2′,6′-dimethyl- and α,2′,6′-trimethyltyrosine and -phenylalanine derivatives via alkylation of chiral equivalents of nucleophilic glycine and alanine

Vadim A. Soloshonok, Xuejun Tang, Victor J Hruby

Research output: Contribution to journalArticle

81 Citations (Scopus)

Abstract

Asymmetric synthesis of (S)-2′,6′-dimethyltyrosine (DMT), (S)-2′,6′-dimethylphenylalanine (DMP), (S)-α,2′,6′-trimethyltyrosine (α-TMT) and (S)-α,2′,6′-trimethylphenylalanine (α-TMP) via reactions of 4′-benzyloxy-2′,6′-dimethylbenzyl bromide or 2′,6′-dimethylbenzylbromide with Ni(II)-complexes of the chiral Schiff base of glycine or alanine with (S)-o-[N-(N-benzylprolyl)amino]benzophenone were developed. Inexpensive and readily available reagents and solvents, a recyclable chiral auxiliary, simplicity of the experimental procedures and high chemical yields make this method synthetically attractive for preparing the target amino acids on a multi-gram scale.

Original languageEnglish (US)
Pages (from-to)6375-6382
Number of pages8
JournalTetrahedron
Volume57
Issue number30
DOIs
StatePublished - Jul 23 2001

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Schiff Bases
Alkylation
Phenylalanine
Bromides
Alanine
Glycine
Derivatives
Amino Acids
benzophenone

Keywords

  • Alkylation reactions
  • Amino acids
  • Asymmetric synthesis
  • Nickel(II) complexes

ASJC Scopus subject areas

  • Biochemistry
  • Organic Chemistry
  • Drug Discovery

Cite this

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title = "Large-scale asymmetric synthesis of novel sterically constrained 2′,6′-dimethyl- and α,2′,6′-trimethyltyrosine and -phenylalanine derivatives via alkylation of chiral equivalents of nucleophilic glycine and alanine",
abstract = "Asymmetric synthesis of (S)-2′,6′-dimethyltyrosine (DMT), (S)-2′,6′-dimethylphenylalanine (DMP), (S)-α,2′,6′-trimethyltyrosine (α-TMT) and (S)-α,2′,6′-trimethylphenylalanine (α-TMP) via reactions of 4′-benzyloxy-2′,6′-dimethylbenzyl bromide or 2′,6′-dimethylbenzylbromide with Ni(II)-complexes of the chiral Schiff base of glycine or alanine with (S)-o-[N-(N-benzylprolyl)amino]benzophenone were developed. Inexpensive and readily available reagents and solvents, a recyclable chiral auxiliary, simplicity of the experimental procedures and high chemical yields make this method synthetically attractive for preparing the target amino acids on a multi-gram scale.",
keywords = "Alkylation reactions, Amino acids, Asymmetric synthesis, Nickel(II) complexes",
author = "Soloshonok, {Vadim A.} and Xuejun Tang and Hruby, {Victor J}",
year = "2001",
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TY - JOUR

T1 - Large-scale asymmetric synthesis of novel sterically constrained 2′,6′-dimethyl- and α,2′,6′-trimethyltyrosine and -phenylalanine derivatives via alkylation of chiral equivalents of nucleophilic glycine and alanine

AU - Soloshonok, Vadim A.

AU - Tang, Xuejun

AU - Hruby, Victor J

PY - 2001/7/23

Y1 - 2001/7/23

N2 - Asymmetric synthesis of (S)-2′,6′-dimethyltyrosine (DMT), (S)-2′,6′-dimethylphenylalanine (DMP), (S)-α,2′,6′-trimethyltyrosine (α-TMT) and (S)-α,2′,6′-trimethylphenylalanine (α-TMP) via reactions of 4′-benzyloxy-2′,6′-dimethylbenzyl bromide or 2′,6′-dimethylbenzylbromide with Ni(II)-complexes of the chiral Schiff base of glycine or alanine with (S)-o-[N-(N-benzylprolyl)amino]benzophenone were developed. Inexpensive and readily available reagents and solvents, a recyclable chiral auxiliary, simplicity of the experimental procedures and high chemical yields make this method synthetically attractive for preparing the target amino acids on a multi-gram scale.

AB - Asymmetric synthesis of (S)-2′,6′-dimethyltyrosine (DMT), (S)-2′,6′-dimethylphenylalanine (DMP), (S)-α,2′,6′-trimethyltyrosine (α-TMT) and (S)-α,2′,6′-trimethylphenylalanine (α-TMP) via reactions of 4′-benzyloxy-2′,6′-dimethylbenzyl bromide or 2′,6′-dimethylbenzylbromide with Ni(II)-complexes of the chiral Schiff base of glycine or alanine with (S)-o-[N-(N-benzylprolyl)amino]benzophenone were developed. Inexpensive and readily available reagents and solvents, a recyclable chiral auxiliary, simplicity of the experimental procedures and high chemical yields make this method synthetically attractive for preparing the target amino acids on a multi-gram scale.

KW - Alkylation reactions

KW - Amino acids

KW - Asymmetric synthesis

KW - Nickel(II) complexes

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U2 - 10.1016/S0040-4020(01)00504-X

DO - 10.1016/S0040-4020(01)00504-X

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JO - Tetrahedron

JF - Tetrahedron

SN - 0040-4020

IS - 30

ER -