Haem d1: stereoselective synthesis of the macrocycle to establish its absolute configuration as 2R,7R1

Abstract

Although the gross structure of haem d₁ 1 has been established, the absolute stereochemistry at C-2 and C-7 is unknown. An unambiguous stereoselective synthesis of the ester of the metal-free macrocycle corresponding to haem d₁ has been completed which establishes the absolute configuration of the natural cofactor as 2R,7R. Haem d₁ is thus shown to match stereochemically other biologically important macrocycles, e.g. those involved in the biosynthesis of vitamin B₁₂, which are related to isobacteriochlorins and also display 2R,7R configurations. The synthetic sequence used is based on a new procedure for assembly of the western and eastern building blocks and it serves as an efficient general route for construction of isobacteriochlorins.