A reappraisal of the Ni-[(Benzylprolyl)amino]benzophenone complex in the synthesis of α,α-disubstituted amino acid derivatives

Morag E. Watson, Craig Jamieson, Alan R. Kennedy, Andrew M. Mason

Research output: Contribution to journalArticle

Abstract

α,α-Disubstituted alkenyl amino acid derivatives (e.g. Fmoc-S 5-OH) are valuable monomers in the construction of stapled peptide derivatives. Synthetic access to these is possible using the Ni-[(Benzylprolyl)amino]benzophenone (BPB) complex as a chiral auxiliary. We discuss a reappraisal of the use of this, and demonstrate that epimerisation of the proline α-centre occurs during formation of the complex, leading to erosion in the enantiomeric excess of the final product. Modified conditions have been developed, providing the target compounds in high enantiomeric excess.

LanguageEnglish
Article number130485
JournalTetrahedron
Volume75
Issue number36
Early online date27 Jul 2019
DOIs
Publication statusPublished - 6 Sep 2019

Fingerprint

Proline
Derivatives
Amino Acids
Peptides
Erosion
Monomers
benzophenone

Keywords

  • amino acids
  • chiral auxiliary
  • peptide staples

Cite this

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title = "A reappraisal of the Ni-[(Benzylprolyl)amino]benzophenone complex in the synthesis of α,α-disubstituted amino acid derivatives",
abstract = "α,α-Disubstituted alkenyl amino acid derivatives (e.g. Fmoc-S 5-OH) are valuable monomers in the construction of stapled peptide derivatives. Synthetic access to these is possible using the Ni-[(Benzylprolyl)amino]benzophenone (BPB) complex as a chiral auxiliary. We discuss a reappraisal of the use of this, and demonstrate that epimerisation of the proline α-centre occurs during formation of the complex, leading to erosion in the enantiomeric excess of the final product. Modified conditions have been developed, providing the target compounds in high enantiomeric excess.",
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A reappraisal of the Ni-[(Benzylprolyl)amino]benzophenone complex in the synthesis of α,α-disubstituted amino acid derivatives. / Watson, Morag E.; Jamieson, Craig; Kennedy, Alan R.; Mason, Andrew M.

In: Tetrahedron, Vol. 75, No. 36, 130485, 06.09.2019.

Research output: Contribution to journalArticle

TY - JOUR

T1 - A reappraisal of the Ni-[(Benzylprolyl)amino]benzophenone complex in the synthesis of α,α-disubstituted amino acid derivatives

AU - Watson, Morag E.

AU - Jamieson, Craig

AU - Kennedy, Alan R.

AU - Mason, Andrew M.

PY - 2019/9/6

Y1 - 2019/9/6

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AB - α,α-Disubstituted alkenyl amino acid derivatives (e.g. Fmoc-S 5-OH) are valuable monomers in the construction of stapled peptide derivatives. Synthetic access to these is possible using the Ni-[(Benzylprolyl)amino]benzophenone (BPB) complex as a chiral auxiliary. We discuss a reappraisal of the use of this, and demonstrate that epimerisation of the proline α-centre occurs during formation of the complex, leading to erosion in the enantiomeric excess of the final product. Modified conditions have been developed, providing the target compounds in high enantiomeric excess.

KW - amino acids

KW - chiral auxiliary

KW - peptide staples

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