Synthesis of dehydrosinefungin and related 4-exo-alkylidene furanoses as novel building blocks for medicinal chemistry (FWOTM817)

The natural product dehydrosinefungin was isolated from microorganisms in 2010 and showed to posses antibiotic properties. This compound is a conjugate of an adenosine (nucleoside) and an ornithine (amino acid) part and has recently attracted interest as nucleoside analogue with potential in antiviral and anticancer research. Unfortunately, no total synthesis of dehydrosinefungin has been described today. The development of methods that allow the preparation of this natural product and related analogues that include the specific central furanose sugar is therefore of high importance. The goal of this project is not only to accomplish the first total synthesis of this pharmaceutical tool compound, but also to explore a variety of synthetic ways towards (E)-4-exo-alkylidene furanose derivatives. The latter compounds are the core structure of dehydrosinefungin and are valuable building blocks to synthesize a variety of novel bioactive nucleoside analogues via transformations of the present double bond. A literature study showed that the chemistry of these specific furanose compounds is not studied in depth. With this project, synthetic pathways will be developed to accomplish new regio- and stereoselective methods to prepare these compounds. With the obtained results, medicinal chemists will be able to use these building blocks in medicinal programs aimed at novel anticancer or antiviral drugs (the main application fields of nucleoside analogues).

Keywords:medicinal chemistry, dehydrosinefungin

Disciplines:Clinical chemistry