Chemoenzymatic Total Synthesis of Complex Terpenoid Natural Products

With the support of the Chemical Synthesis (SYN) program in the Division of Chemistry Professor Hans Renata of Rice University is studying the development of novel strategies to prepare complex terpenoids, which are natural, hydrocarbon-based small molecules. Owing to their structural complexity, synthesizing these molecules with purely chemical means remains a challenging endeavor. The proposed research will combine the use of enzymes, which are nature’s catalysts for chemical reactions, with modern chemical transformations to provide efficient access to many topologically complex terpenoids. This investigation will provide new knowledge in chemical reactivity and new insights in synthetic strategy development that will inform the synthesis design of other topologically-challenging molecules. Trainees working on this project will be exposed to cutting edge techniques in contemporary chemical synthesis and biocatalysis to prepare them for future careers in the chemical industry. In conjunction, Professor Renata will organize outreach efforts and scientific demonstrations to high school students, and virtual lecture series by faculty members from primarily undergraduate institutions (PUIs). Research in the Renata lab focuses on the development of hybrid chemoenzymatic strategies in the synthesis of complex molecules, especially natural products. The goal of this project is to develop several hybrid synthetic approaches to complex terpenoids with various skeletal connectivities and topologies. Specifically, site-selective enzymatic oxidations with engineered P450 variants will be used in combination with modern methodologies in organic chemistry, such as radical cross-couplings, to provide rapid synthetic access to the proposed targets. Additionally, they will explore the use of enzymatically installed hydroxyl groups as a starting point to effect skeletal reorganization to prepare a diverse range of terpenoid frameworks. To complement the research activities, educational activities such as scientific demonstrations to promote interest in the STEM field from the local community, virtual lecture series and workshops on biocatalysis will be carried out. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.