Stereoselective retro-synthetic analysis

The key point of the total synthesis is the stereoselective construction of the high-congested tetrahydrofuran ring. The synthetic route is shown in the retro-synthetic analysis. There are two synthetic routes (1) directly construct a seven-membered ring then followed by an IMDA reaction to construct the natural product s skeleton with tetrahydrofuran ring in one single step (2) modify the product of IMDA reaction to obtain compound 2. Both of these two strategies can be connected to the key intermediate 5, which could be obtained by reduction of 1,3-keto esters 6. 

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