New Ion‐Exchange cum Separation Technique: A Study for the Synthesis of ω‐Guanidine containing Peptides using ω‐Amino Acid as Surrogate

Abstract

This article describes a systematic study for the introduction of ω‐guanidine function at a late stage of synthesis using a protected amino group as a surrogate to improve overall yield. This concept was used to design and synthesize pseudo‐peptides as GP IIb–IIIa receptor antagonist wherein glycine in endogenous ligand Arg‐Gly‐Asp (RGD) is replaced by 2‐amino‐thiazole‐4‐ylacetic acid (Tha) as a spacer. Further, we describe here a unique salt exchange cum purification technology based on reverse phase (RP‐18) medium‐pressure liquid chromatography.

Keywords:

• amino group as surrogate
• GP IIb–IIa
• RGD
• salt exchange cum RP‐18 purification
• ω‐guanidine function

Acknowledgments

We gratefully acknowledge J. Blumbach for his interest and encouragement, V. S. V. V. Rao and R. D. Gupte from the pharmacological department for screening the compounds, and P. K. Inamdar and his group for providing analytical data. Finally, we acknowledge A. Ranade for providing useful literature input.