Total Synthesis of Chloptosin: A Dimeric Cyclohexapeptide

Alexander J. Oelke ; Francesca Antonietti ; Leonardo Bertone ; Philippa B. Cranwell ; David J. France ; Rebecca J. M. Goss ; Tatjana Hofmann ; Stephan Knauer ; Steven J. Moss ; Paul C. Skelton ; Richard M. Turner ; Georg Wuitschik ; Steven V. Ley

Chemistry – A European Journal 2011, 17 (15) 4183-4194

Here we describe in full our investigations into the synthesis of the dimeric cyclohexapeptide chloptosin in 17 linear steps. Particularly, this work features an organocatalytic tandem process for the synthesis of the embedded piperazic acids, in which a differentially protected azodicarboxylate is used together with pyrrolidinyl tetrazole as the catalyst. The central biaryl bond is being formed by Stille coupling of two sterically demanding ortho-chloropyrroloindole fragments. The inherent flexibility of the synthetic strategy proved beneficial as the route could be adjusted smoothly during the progression of the synthesis programme.