Total Synthesis of Tedanolide C

The aim of this post-doctoral research proposal consists of two parts: First, the development of two new extensions of a recently devised methodology and second the first total synthesis of a complex natural product. The research group of Prof. W. R. Roush were the first who succeeded in performing a double allylboration reaction in 2002. This methodology proved to be a highly valuable tool as demonstrated in its application during various total syntheses. An extension of the originally elaborated protocol should allow the introduction of additional functionality into the chiral allyl-carrier. For that purpose, two new extensions were outlined: The introduction of complex alkyl-groups on the C1-position of the allyl-unit and the introduction of silyl-groups on the C3-position of the allyl-carrier. These extensions will allow the rapid access towards complex structural features found at various natural products in an easily performable one-pot fashion. Both methodologies should be devised to general procedures that should allow convergent retrosynthetic analyses for the total synthesis in future. The total synthesis of tedanolide C (10) represents a challenge for a total synthesis due to several reasons. This recently isolated natural product still misses any synthetic work. Furthermore, a total synthesis has to prove the originally assigned structure of the target as well as to reveal the absolute stereochemistry of this stereochemically congested molecule. Additionally, the total synthesis of tedanolide C (10) represents a way to ensure sufficient supply with this biologically active compound for future structure-relationship studies. This proposal outlines a unique total synthesis of the target molecule. A highly convergent fragment assembly step completes the preparation of the overall carbon-skeleton of tedanolide C (10) and introduces requisite functionality stereospecifically at the same time in a single step. The research plan outlines a synthesis of the two requisite fragments A and B. For the synthesis of the synthetically more demanding fragment B three independent routes are presented. The key step which represents a complete novelty is described in detail as well as a pathway towards the completion of the synthesis. In comparison with total syntheses of other members of the family of this natural product, the proposed total synthesis of tedanolide C (10) does not only apply unprecedented methodology but is also characterised by shortest number of synthetic steps.