Discodermolide : Total Synthesis of Natural Product and Analogues
Résumé
This account describes an efficient and modulable total synthesis of (+)-discodermolide and analogues. Particularly notable is the repeated application of a crotylation reaction of aldehydes, with α-oxygenated crotyltitanium reagent to ensure the stereocontrolled elaboration of syn–anti methyl-hydroxy-methyl triads connected to a Z-O-enecarbamate. This particular group allowed direct and easy access to either a triple bond or terminal Z-diene function. The stereocontrolled generation of the trisubstituted Z-double bond, representing a significant synthetic challenge, is ensured by a 1,2-dyotropic rearrangements on dihydrofuran with organocopper reagents. The synthesis of natural product was achieved in 21 steps with 1.6% overall yield. The same methodologies and synthetic strategy were applied for the preparation of five original analogues. The biological activities of natural product and synthetic analogues have also been studied.
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