Macrolactamization via Palladium Alkylation. Preparation of C6S25155: A 10-Membered Lactam Neutral Endopeptidase 24.11 Inhibitor

摘要

We have developed an extension of Pd π-allyl alkylations that gives access to a 10-membered lactam in good yield and applied the methodology to the preparation of CGS25155, an NEP 24.11 inhibitor. Several features of the present synthesis are advantageous in comparison with the initial synthesis. These include avoiding the need for chiral auxiliary-based resolution, more direct introduction of the methylene at C-9, and enhanced stereoselectivity in the thioacetate 1,4-addition.