HEME D(1) - STEREOSELECTIVE SYNTHESIS OF THE MACROCYCLE TO ESTABLISH ITS ABSOLUTE-CONFIGURATION AS 2R,7R

Although the gross structure of haem d(1) 1 has been established, the absolute stereochemistry at C-2 and C-7 is unknown, An unambiguous ste reoselective synthesis of the ester of the metal-free macrocycle corre sponding to haem di has been completed which establishes the absolute configuration of the natural cofactor as 2R,7R. Haem d(1) is thus show n to match stereochemically other biologically important macrocycles, e.g. those involved in the biosynthesis of vitamin B-12, which are rel ated to isobacteriochlorins and also display 2R,7R configurations, The synthetic sequence used is based on a new procedure for assembly of t he western and eastern building blocks and it serves as an efficient g eneral route for construction of isobacteriochlorins.