Synthesis of Thromboxane and Monofluorinated Analogues

• Applicant: Dr. Hannah Baars
• Subject Area: Organic Molecular Chemistry - Synthesis and Characterisation ; Pharmacology
• Term: from 2016 to 2017
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 329283583

• Final Report Year: 2017

Final Report Abstract

In summary, progress in three mayor parts of the project were made. First, the olefination step was optimized and now a fully stereocontrolled and efficient synthesis for PGI2-F was achieved. Second, straight forward synthesis for the other side chains had been developed. Third, a new 1,4-addition of alkynes was established. Its advantages were demonstrated in the revisited synthesis of PGF2α and in the synthesis of Alfaprostol. In the future, the other targets will be synthesized by another postdoc. For the alkene target 2 the same route as for PGI2-F and PGI2-F2 will be used. For the alkyne targets 3 and 4 the new developed 1,4-addition will be applied. It is expected that all steps can be adopted. Once synthesized the targets will be tested on activity and selectivity towards the Prostacyclin receptor and stability.

Publications

• „Synthesis of Alfaprostol and PGF2α through 1,4-Addition of an Alkyne to an Enal Intermediate as the Key Step”. Org. Lett. 2017, 19, 6008–6011
  H. Baars, M. J. Classen, V. K. Aggarwal
  (See online at https://doi.org/10.1021/acs.orglett.7b03057)