Organic synthesis constitutes the enabling science for the creation of new compositions of matter with ramifications for material’s science, medicine and biology. Our research program is dedicated to the understanding and modulation of biologically relevant pathways with small molecules. Toward this end, we are creating natural product inspired structures that are otherwise inaccessible. Overcoming some of the limitations of multistep synthesis along this way poses a constant challenge that keeps us alive and kicking.
Our target-oriented synthesis program is concerned with the synthesis of biologically relevant molecules. An overreaching theme in our strategic design is the minimization of carbon-carbon bond formations. Instead, we invest in the selective functionalization of larger (terpene-) building blocks. We have challenged this approach in the synthesis of the telomerase inhibitor UCS1025A, the RNA polymerase inhibitor ripostatin B and the guaiane sesquiterpenoid englerin A - a compound that exhibits high selectivity against several renal cancer cell lines.
Our approach to method development is best described as problem-driven. In this regard, we aim to identify new transformations that shortcut synthetic sequences to substructures within our targeted molecules. In particular, we have been interested in the use of organocatalytic reactions in total synthesis. Organocatalysis has emerged as an efficient solution for the rapid and stereoselective synthesis of chiral chemical entities. In a mechanistically motivated program, we have been investigating reactivity of electron-rich dienamines as intermediates in catalysis.
We have recently initiated a program that is aimed at making larger substructures within natural products available from terpene feedstock. Using simple bulk terpenes such citronellal, geranyl and neryl acetate or nepetalactone, we have been able to find efficient ways to modify the carbon skeleton using oxidations, organocatalytic and metal-catalyzed reactions such as hydroformylations.