Chiral heterocyclic compounds typically display interesting biological activity, and are commonly found in marketed pharmaceuticals. The broad aim of this research is to develop new synthetic methods for preparing chiral heterocyclic compounds that are difficult to access otherwise. The first part of this research involves the development of an asymmetric Pd(ll)-catalyzed Sn2'displacement of prochiral allylic trichloroimidates with C-H acids as nucleophiles. Subsequently, this methodology will be applied to prepare the contiguous quaternary stereocenters of Hyperolactone C in a stereoselective fashion. The final section of the proposed research will apply chiral Pd(ll)-catalysts in cascade reactions to prepare useful heterocyclic compounds.
Many new pharmaceuticals introduced in the last 10 years are marketed as single-enantiomer drugs. Further, many of these compounds contain heterocyclic structures. The proposed research will provide scientists, primarily medicinal chemists in the pharmaceutical industry, new synthetic tools for the preparation of single-enantiomer heterocyclic compounds and for the discovery of new drugs.
| Altman, Ryan A; Nilsson, Bradley L; Overman, Larry E et al. (2010) Total synthesis of (+)-nankakurines A and B and (±)-5-epi-nankakurine A. J Org Chem 75:7519-34 |
