Recently we developed a method for the generation of the stable N-methylaziridium ion from 2-substituted [(1S)-phenylethyl]aziridine and the subsequent ring opening with various nucleophiles to yield cyclic and acyclic N-methylamines in enantiomerically pure forms.  Application of this method allowed us for the total synthesis of natural product tyroscherin and it's derivatives. Tyroscherin was isolated from the mycelium of Pseudallescheria sp. as a potent and selective inhibitor of IGF-1-dependent growth of MCF-7 human breast cancer cell. The key step of this synthesis involves methylation and the following arylative ring opening of (S)-2-((R)-10,10-diisopropyl-2,2,3,3,11-pentamethyl-4,9-dioxa-3,10-disiladodecan-5-yl)-1-((S)-1-phenylethyl)aziridine with (4-substituted phenyl)magnesium bromide to yield the ring opened product. Application of diverse arylative nucleophiles allowed us to afford the tyroscherin derivatives bearing the substutient other an hydroxy group at the aryl ring.

Synthesis of tyroscherin and it's derivatives

244th National Meeting (2012)

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