Advancements in Enacyloxins Total Synthesis: Access to the Chlorinated Polyunsaturated Chain Peculiar to this Promising Family of Antibiotics.

The first synthesis of the protected chain specific to the enacyloxin antibiotic family is reported. The noticeable features are (a) the construction of the chlorinated undecapentaenoic moiety implementing the sequence Tsuji's alkyne syn allyl-chlorination, E-selective Pd/Cu-catalyzed allene-alkyne coupling, Horner-Wadsworth-Emmons olefination, dehydration; (b) control of the C18 chlorinated stereogenic center by organo-catalyzed aldehyde α-chlorination; and (c) the assemblage of this aldehyde with the C1-C16 ketone using a highly diastereoselective Mukaiyama aldol.