Total Synthesis of Mirabalin isomers and Simplified analogs – STIMAS

Six fragment have been design to built up the molecule
Stereoselective aldolisations, selective couplings, metatheses, enantioselective allylations, Marshall reactions and enantioselective reductions have been used to synthesize the different fragments.

On the six fragments, five have been synthesized as well as two advanced precursors to access the sixth one.

Complete the synthesis of the sixth fragment and then to achieve the coupling in between all the synthesized fragments in order to access mirabaline
The synthesis of analogues will then be realized.

Two publications will be submitted in the near future in international journals.

The total synthesis of complex natural products is a real challenge for synthetic chemists worldwide and has led to considerable advances in the field of organic chemistry. In this context, mirabalin, a new macrocyclic lactam isolated from the sea sponge siliquariaspongia mirabilis, is a significant synthetic target because of its antitumor activity and the complexity of its structure that contains 25 stereogenic centers, several of which have not yet been determined. This project aims to synthesize four isomers of this molecule as well as four simplified analogs in order to contribute to the assignment of the relative configurations of the stereogenic centers of mirabaline and to realize structure-activity relationship studies. The association of organic chemists of the ESPCI and ENSCP having expertise in total synthesis, offers a unique opportunity to combine their complementary know-how in the field of synthetic methodologies in order to develop an efficient access to a complex natural molecule that has never been synthesized.