Stereoselective Reduction of Pyrrole and Furan Compounds

Heterocycles are important units within organic chemistry and feature in many biologically potent natural products (alkaloids, polyether antibiotics, acetogenins), exhibiting a number of promising biological properties including antitumor, antimalarial, antimicrobial, immuno-suppressant, anti-feedant, and pesticidial activity. The continued interest in heterocyclic chemistry and the transformation of aromatic heterocycles (pyrrols and furans) in particular, is an interesting area of research because heterocyclic compounds constitute a great majority of active agents for both, the pharmaceutical and agrochemical industries. The partial catalytic redution of pyrroles and furans represents a new way for the synthesis of highly functionalised heterocycles, gaining access to five-membered ring heterocycles (pyrrolidines, pyrrolizidines, tetrahydrofurans). This is a versatile method capable of producing useful stereochemically defined templates for the synthesis of a wide range of biologically active compounds (pyrrolidine and pyrrolizidine alkaloids, marine based tetrahydrofurans). By investigating the reation conditions in detail, we aim to be able to produce enantiopure building blocks in a very efficient way under complete control of stereochemistry. This will overcome the drawbacks of conventional syntheses, e.g. ending up in racemic mixtures or the necessity of using expensive chiral auxiliaries to control absolute stereochemistry. These building blocks are used as valuable starting materials in stereoselective total synthesis of e.g. the two rather complex natural product alkaloids hyacinthacine C1 and alexine. In addition, the transferability and extension of this methodology from the class of nitrogen ring systems to the class of highly functionalised tetrahydrofurans should be investigated.