Concise total synthesis of the potent translation and cell migration inhibitor lactimidomycin.
An efficient total synthesis of the antiproliferative macrolide and cell migration inhibitor lactimidomycin (3) is reported, which relies on the performance of ring closing alkyne metathesis (RCAM). The strained 12-membered 1,3-enyne 21 as the key intermediate was forged with the aid of [(Ph(3)SiO)(3)Mo≡CPh]·OEt(2) (27) as the most effective member of a new generation of powerful alkyne metathesis catalysts. 21 was elaborated to the target by a ruthenium catalyzed trans-hydrosilylation/proto-desilylation sequence and a highly diastereoselective Mukaiyama aldol reaction controlled by oxazaborolidinone 29 as strategic operations.
Micoine
Kevin
K
Max-Planck-Institut für Kohlenforschung, D-45470 Mülheim/Ruhr, Germany.
Fürstner
Alois
A
D000818:Animals; D002465:Cell Movement / Q000187:drug effects*; D006801:Humans; D018942:Macrolides / Q000138:chemical synthesis* / Q000494:pharmacology; D010881:Piperidones / Q000138:chemical synthesis* / Q000494:pharmacology; D014176:Protein Biosynthesis / Q000187:drug effects*
D018942:Macrolides; D010881:Piperidones; C077633:lactimidomycin