Facile Synthesis of 7-Alkyl-1,2,3,4-tetrahydro-[1,8]-naphthyridines as Arginine Mimetics Using a Horner–Wadsworth–Emmons Based Approach

  1. Rhys A Lippa,
  2. John A Murphy and
  3. Tim BarrettORCID Logo

Submitting author affiliation: GSK, Stevenage, United Kingdom

Beilstein Arch. 2020, 202055. https://doi.org/10.3762/bxiv.2020.55.v1

Published 27 Apr 2020

  • Preprint


Integrin inhibitors based on the tripeptide sequence Arg-Gly-Asp (RGD) are potential therapeutics for the treatment of idiopathic pulmonary fibrosis (IPF). Herein, we describe an expeditious three-step synthetic sequence of Horner–Wadsworth–Emmons olefination, diimide reduction and global deprotection to synthesise cores for these compounds in high yields (63–83% over 3 steps) with no need for chromatography. Key to this transformation is the phosphoramidate protecting group, which is stable to metalation steps.

Keywords: Arginine; Horner–Wadsworth–Emmons; Integrin; Phosphoramidate; Tetrahydronaphthyridine

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Lippa, R. A.; Murphy, J. A.; Barrett, T. Beilstein Arch. 2020, 202055. doi:10.3762/bxiv.2020.55.v1

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