Two-Phase Taxane Total Synthesis

• Applicant: Dr. Insa Prochnow-Sturm
• Subject Area: Organic Molecular Chemistry - Synthesis and Characterisation
• Term: from 2012 to 2014
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 218471545

Taxanes represent a large family of terpenes comprising over 300 natural products, of which many exhibit cytotoxic activity against various types of cancer, and also display interesting neurological and antibacterial properties. The most celebrated example of these diterpenoids is the drug Taxol® (paclitaxel).Despite the extraordinary complexity, the biosynthesis of taxanes takes place in a unified fashion by a two-phase approach composed of cyclase phase and oxidase phase. In the first phase, a simple linear hydrocarbon phosphate building block is converted into the taxane carbon framework by enzymatically controlled cyclizations and rearrangements (cyclase phase). In the second phase, alkenes and sp3-C-H bonds are chemo-, regio-, and stereoselectively oxidized by enzymatically controlled oxidations to result in a large array of biologically active compounds (oxidase phase).Inspired by the impressive efficiency of this biosynthesis, a biomimetic two-phase terpene total synthesis was developed in the Baran laboratory. Within the planned project, a variety of taxanes should be synthesized using this two-phase strategy. In order to create a number of highly functionalized taxanes, a taxane skeleton with minimal oxidation adornment would be first constructed during the cyclase phase. Oxidized taxanes would then be targeted by directed or remote C-H oxidation of the taxane hydrocarbon framework during the oxidase phase. Because of ist efficiency this strategy would constitute a divergent approach to the entire family of taxane natural products.

• DFG Programme: Research Fellowships
• International Connection: USA
• Host: Professor Phil S. Baran, Ph.D.