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Division of Science, Mathematics, and Computing presents

Cascade Reactions with Alkynes

Synthesis of the Antimitotic Agent Podophyllotoxin via Pd(II)-Catalyzed Reactions

Friday, February 22, 2013

A lecture by
Jason Abrams
Candidate for the Position in Chemistry

This talk seeks to highlight new routes toward the construction of the aryltetralignan podophyllotoxin (Figure 1).  Podophyllotoxin (1) is a precursor for clinically employed chemotherapy drugs such as etoposide and teniposide, and itself exhibits a mechanistically understood antineoplastic effect.  Understandably these architecturally intriguing compounds have gained the attention of the scientific community and have resulted in several syntheses.  However, with poor solubility and increasing drug resistance, there exists a need to develop new complementary approaches towards these important therapeutic agents. 

In this regard, the synthetic route towards podophyllotoxin has been crafted to be flexible, and amenable to analog development.  A common theme for the newly developed route involves exploitation of the unique reactivity of alkynes, by incorporating recently developed methods into novel reaction sequences.  Beyond the preparation of an important natural product with antineoplastic activity, the rationale for research as highlighted in the talk is an expansion of the utility of a unique Pd(II)-catalyzed enyne cyclization method by highlighting its utility towards natural product synthesis.  In addition to a first and second generation route towards the ABCD ring system of podophyllotoxin, proposed future plans will be discussed including podophyllotoxin end-game completion, modifications to the biologically crucial E-ring, elaboration of an unusual tetralone byproduct, among others.

Location: RKC 115