Total Synthesis of Hypothemycin

aldehyde 563 was obtained by reprotectitMi of the alkyne with subsequent selective cleavage of the TBS ether and Swem oxidatitm. 

A further synthesis of hypothemycin (481) was published by the group of Winssinger in 2009 (384). They used a partial solid-phase strategy with a benzylic sulfide linker to build up the resorcylic macrolactone. The applied macrolacto-nization step proceeded extremely efficiently and epoxidation of LL-Zl640-2 (567) with dimethyldioxirane afforded hypothemycin with excellent regio- and stereoselectivity, but in a poor yield. 

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