BIOSYNTHESIS OF UROPORPHYRINOGENS - SYNTHESIS OF ALPHA-AMINOMETHYLBILANES AND THEIR INTERACTION WITH THE ENZYMATIC SYSTEM

The synthesis of α-aminomethylbilanes of biosynthetic interest is described. It is based on synthesis of conveniently prepared 6-bilene hydrobromides in which the α-unsubstituted position was protected by suitable esters, and the aminomethyl group was protected in the form of a six-membered lactam ring with a terminal acetic acid residue. Hydrogenation of the bi-lenes, cleavage of the protecting esters, and saponification of the lactam rings and side-chain esters led to α-aminomethylbilanes. An α-aminomethylbilane that is formally derived from the self-condensation of four units of porphobilinogen was examined as a possible biosynthetic intermediate of uroporphyrinogen biosynthesis. It was not found to be a substrate of either porphobilinogen deaminase, uroporphyrinogen III cosynthase, or the deaminase-cosynthase system. The same amount of total uroporphyrinogens was formed by the chemical cyclization of the bilane in the absence or presence of enzymes. The chemical cyclization of the bilane was found to give almost exclusively uroporphyrinogen 1 (93-100%). No enzymatic formation of uroporphyrinogen III at expense of the bilane was detected. An inhibitory effect of the bilane on the enzymatic formation of uroporphyrinogen III from porphobilinogen was observed. © 1979, American Chemical Society. All rights reserved.