Total synthesis of (-)-pulvomycin

• Applicant: Professor Dr. Thorsten Bach
• Subject Area: Organic Molecular Chemistry - Synthesis and Characterisation
• Term: from 2013 to 2021
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 236307437

(-)-Pulvomycin is a complex polyketide natural product with a molecular mass of 839 Da, which effectively inhibits the bacterial elongation factor EF-Tu. Structurally, pulvomycin can be divided into a 22-membered macrolactone (eastern fragment) and a linear chain (western fragment), which is connected via a beta-glycosidic bond to labilose, a 6-desoxygalactose. So far, neither a total synthesis of this natural product nor partial syntheses of its individual fragments have been reported. In this project a convergent total synthesis of (-)-pulvomycin is proposed, which is based on the above-mentioned division of the molecular skeleton. The synthetic strategy takes the high lability of the natural product into account, which will be better understood by the synthesis of the individual fragments. The macrolactone of the eastern fragment bears particular importance for the biological activity because plays the major role in binding the biological target molecule. EF-Tu has been previously validated as a target for the development of new antibiotics.

• DFG Programme: Research Grants