Pyrroles and related compounds. Part XXXIII. Total synthesis of deuteriated derivatives of protoporphyrin-IX for nuclear magnetic resonance studies of haemoproteins

Abstract

In order to settle the precise identity of certain resonances in the paramagnetic n.m.r. spectra of low-spin haemoproteins, a variation of the MacDonald approach to porphyrins from pyrromethanes has been developed and applied to the synthesis of protoporphyrin-IX dimethyl ester (1a) and its 5,8-bis(trideuteriomethyl)-, 1,3-bis(trideuteriomethyl)-, and αγ-dideuterio-derivatives [(1b), (1d), and (14b), respectively]. Synthesis of 1,8-bis(trideuteriomethyl)protoporphyrin-IX dimethyl ester (1c) by the b-oxobilane route completed the series to be used for unambiguous assignment of the four methyl resonances in the contact shift n.m.r. spectra of the corresponding iron(III) cyanides.

Deuterium was incorporated into the porphyrins by total synthesis from the appropriate deuteriated pyrroles, which were in turn synthesised from deuteriated 1,3-diketones by standard methods. Novel exchange processes were discovered and used to achieve deuteriation at the interpyrrolic carbon atoms of pyrromethanes and at opposite meso-positions of porphyrins prepared by the MacDonald method.