Synthesis of model southern rim structures of photosynthetic tetrapyrroles and phyllobilins

The photosynthetic tetrapyrroles and their catabolic products (phyllobilins) share similar structural features in the southern rim encompassing rings C-E with variation in the degree of saturation including a dihydrodipyrrin (chlorophyll a and bacteriochlorophyll a), a dipyrromethane (phylloleucobilin), and a dipyrrin (chlorophyll c). Here, a direct, two-step route to southern rim structures was examined. The Knoevenagel condensation of a pyrrole bearing a & beta;-ketoester at the 3-position with a pyrrole-2-carboxaldehyde formed the dipyrrole-substituted propenone, which upon Nazarov cyclization gave the dipyrromethane-type southern rim containing the annulated, isocyclic ring. In this manner, three southern rim structures (51-80%) were obtained that vary in the nature of the pyrrole substituents (H, methyl, carbomethoxy). Characterization by H-1 NMR spectroscopy in each case revealed an expected mixture of trans/cis isomers (& SIM;9 : 1 ratio). Several derivatization processes (pyrrole acylation with trichloroacetic anhydride, ketone reduction with borohydrides) were examined. Analysis of one southern rim compound by single-crystal X-ray diffraction showed the trans configuration for the expected pair of enantiomers in the unit cell; a second compound gave the trans enantiomers as a conglomerate. The Knoevenagel-Nazarov route from relatively accessible pyrroles may provide new scaffolds for constructing tetrapyrrole architectures.