Total Synthesis and Medicinal Chemistry of Natural Products

Our research is centered on the chemical synthesis of bioactive natural products/natural product analogs and their biological characterization. Major objectives of our work are (i) the total synthesis of bioactive natural products and their profiling; (ii) the elucidation of the structural requirements for biological activity; (iii) the assessment of opportunities for structural simplification and molecular editing of complex natural products; and (iv) in selected cases, mechanism of action and structural studies. Ultimately, all of these efforts aim at the identification of new leads for drug discovery or potential drug candidates, with a main focus on cancer and infectious diseases. The work in the group is largely chemistry-based, while biological questions are addressed in collaborations with appropriate partners.

Research news

We have developed a highly efficient synthesis of the the aglycone of the antibiotic tiacumicin B (lipiarmycin A3, fidaxomicin). The work has been published in the February issue of Angewandte Chemie International Edition: F. Glaus, K.-H. Altmann. Total Synthesis of the Tiacumicin B (Lipiarmycin A3/Fidaxomicin) Aglycone. Angew. Chem. Int. Ed. 2015, 54, 1937-1940.

Abstract:

The total synthesis of the tiacumicin B aglycone (2) and of partially protected variants thereof has been accomplished based on ring-closure by intramolecular Suzuki cross-coupling. Key steps in in the assembly of the linear macrocyclization precursor were a highly selective one-pot Corey-Peterson olefination (on the way to 5), based on a new thiophenol-mediated Z to E isomerization of an α,β-unsaturated aldimine, and an ene-diene cross metathesis reaction

Teaching

The main teaching responsibilities of the professorship in Pharmaceutical Biology are for a 3 h lecture course that is taught in the fall semester and a 3 week laboratory course that is taught in the spring semester. The lecture course covers basic aspects of the structure and biosynthesis of plant constituents and the pharmacological effects and therapeutic applications of biogenic drugs of plant origin (extract-based herbal medicines; isolated natural products). The laboratory course includes the microscopic analysis of plant material (pharmacopoeia), the chromatographic analysis of medicinal plants, extraction methods, qualitative/quantitative determination of medicinal plant constituents, and the isolation of natural products. For more information please consult the course catalog of the ETH Zürich.

 
 
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Wed Jul 01 02:23:58 CEST 2015
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