Asymmetric synthesis of Boc-N-methyl-p-benzoyl-phenylalanine. Preparation of a photoreactive antagonist of substance P

Bioorg Med Chem Lett. 1998 Jun 2;8(11):1369-74. doi: 10.1016/s0960-894x(98)00219-4.

Abstract

The asymmetric synthesis of (S)-Boc-N-methyl-p-benzoyl-phenylalanine was performed by alkylation of sultam Boc-sarcosinate. The levorotatory sultam led to (S)-Boc-N-methyl amino acids with high optical purity. This photoreactive amino acid was incorporated into the sequence of a Substance P peptide antagonist. Comparison of the affinity and antagonistic properties of Biotinyl-apa-[D-Pro9, MePhe(pBz)10, Trp11]SP for human tachykinin NK-1 receptor demonstrated that this photoreactive antagonist should be a suitable tool for photolabelling studies.

MeSH terms

  • Alkylation
  • Animals
  • Biotin / analogs & derivatives
  • Biotin / chemical synthesis
  • Biotin / chemistry
  • Biotin / pharmacology
  • CHO Cells
  • Cricetinae
  • Cyclic AMP / metabolism
  • Humans
  • Molecular Conformation
  • Neurokinin-1 Receptor Antagonists
  • Phenylalanine / chemical synthesis*
  • Photochemistry
  • Receptors, Neurokinin-2 / metabolism
  • Structure-Activity Relationship
  • Substance P / analogs & derivatives
  • Substance P / antagonists & inhibitors*
  • Substance P / chemical synthesis
  • Substance P / chemistry
  • Substance P / pharmacology

Substances

  • N-(tert-butoxycarbonyl)-N-methyl-4-benzoylphenylalanine
  • Neurokinin-1 Receptor Antagonists
  • Receptors, Neurokinin-2
  • substance P, biotinyl-apa-Pro(9)-MePhe(pBz)(10)-Trp(11)-
  • Substance P
  • Phenylalanine
  • Biotin
  • Cyclic AMP