BIOSYNTHESIS OF PORPHYRINS AND RELATED MACROCYCLES .40. SYNTHESIS OF A SPIRO-LACTAM RELATED TO THE PROPOSED SPIRO-INTERMEDIATE FOR PORPHYRIN BIOSYNTHESIS - INHIBITION OF COSYNTHETASE

Routes are developed for synthesis of the tripyrrolic macrocyclic spir o-lactam 39. A minor product from the synthesis, thought earlier to be an atropisomer, has been shown by molecular mechanics calculations an d re-investigation to be a dimer. The octa-acid derived from 39 closel y resembles the spiro-pyrrolenine 2 proposed as a biosynthetic interme diate for uroporphyrinogen III. This octa-acid acts as a strong inhibi tor of cosynthetase (uroporphyrinogen III synthase) whilst other simil ar systems which lack some of its functionality do not. These results strongly support the view that the spiro system 2 is indeed the biosyn thetic intermediate for formation of uroporphyrinogen III 3 from hydro xymethylbilane 1.