Synthesis of 1,2,5,6-Tetrahydro-3-pyridinylalanine: A Key Intermediate in the Preparation of Thrombin Inhibitor UK-239,326

Abstract

A short synthesis of N-protected 1,2,5,6-tetrahydro-3-pyridinylalanine derivatives (8–10) was accomplished using a simple procedure of quaternization of (3-pyridyl)alanine 6 with benzyl bromide followed by reduction with NaBH₄. Amino acid 10 was then converted to thrombin inhibitor UK-239,326 (2), which required the sequential functionalization of four amines to give four different functional groups (viz., sulfonamide, carboxamide, guanidine, and methylamine).

Keywords:

• Tetrahydropyridinylalanine
• thrombin inhibitors
• UK-239
• 326

ACKNOWLEDGMENT

We thank our colleagues for their expert and enthusiastic technical assistance: Yvonne Ailwood, Leena Patel, and Anthony Pomeroy. We also thank members of the Physical Sciences Group for spectroscopic and analytical services.