Synthetic and mechanistic studies in the tetrapyrrole chemistry

This thesis describes the synthetic study of two biologically related natural products: a linear tetrapyrrole, phytochromobilin and macrocyclic tetrapyrroles, chlorins. In addition, the transition-metal catalyst cross-couplings of thioorganics with alkylzinc reagents are thoroughly investigated.; The D-ring precursor of phytochrome was efficiently synthesized in five steps from butyralactone employing an intramolecular aldol condensation to construct the five-membered ring. The modified D-ring precursor allowed the crucial bond forming step to afford the C,D-ring pyrromethenone to be achieved under mild Lewis acid conditions. This was a significant improvement over the existing methods of preparing such pyrromethenones.; Due to its applications in tumor photodynamic therapy (PDT), an efficient synthesis of chlorins is highly desirable. Our synthesis utilizes a dialdehyde and an unsubstituted dipyrromethane which are condensed in the presence of p-toluenesulfonic acid to afford the chlorin macrocycle in greater than 85% yield. We believe this approach is useful because of its flexibility and the simplicity of the experimental conditions that require no metal activation. In addition, the synthesis is amenable to large scale preparation of chlorins, which may be helpful to evaluate their activity as photosensitizers in PDT.; During the course of preparing diformyl precursors required for our chlorin synthesis we had observed a marked difference in reactivity between isomeric thioimidates towards Pd(0)-catalyzed cross-coupling reactions. The Z-thioimidates readily underwent cross-coupling with McZnI/Pd(0), whereas the corresponding E-isomers were inert to identical conditions. Using these isomeric thioimidates we were able to show that zinc complexation was crucial in promoting oxidative addition in the Z-thioimidates and methythiopyridines. Analogous zinc complexation was not possible in the corresponding E-isomers, and thus oxidative addition and subsequent cross-coupling failed for such compounds.