Synthesis
DOI: 10.1055/s-0036-1588505
paper
© Georg Thieme Verlag Stuttgart · New York

A Short and Scalable Synthesis of Orthogonally Protected Bis(aminomethyl)malonic Acid: Access to Bioactive Macrocyclic Peptides

Muthalagu Vetrichelvan*a, Vijayabhaskar Bokkalaa, Surendran Renganathana, Arvind Mathura, b, Richard Rampullab, Anuradha Guptaa
  • aBiocon-Bristol Myers Squibb R & D Centre, Bommasandra IV Phase, Jigani Link Road, Bengaluru 560099, India
  • bBristol Myers Squibb Company, P. O. Box 4000, Princeton, NJ 08543 4000, USA   Email: muthalagu.vetrichelvan@syngeneintl.com
Further Information

Publication History

Received: 28 April 2017

Accepted after revision: 27 June 2017

Publication Date:
01 August 2017 (eFirst)

Abstract

A short and scalable process for the preparation of multi-gram quantities of orthogonally protected bis(aminomethyl)malonic acid in good yield from readily available starting material is described. These orthogonally protected amino acids are important building blocks to make peptides based drugs, glycoconjugates, and in the total synthesis of peptide natural products. The newly developed route has only six steps with an overall yield of 27%, which involves nucleophilic attack of a malonate on an imide as one of the key steps.

Supporting Information