2 research outputs found
Total Synthesis of (+)-Clavilactone A and (−)-Clavilactone B by Ring-Opening/Ring-Closing Metathesis
The enantioselective total synthesis of natural enantiomers of clavilactones A and B has been achieved. A key feature of the synthesis is the use of a ring-opening/ring-closing metathesis, which allows the one-pot transformation of a strained cyclobutenecarboxylate into a γ-butenolide
Total Synthesis of Clavilactones
Clavilactones
A, B, and D are epidermal growth factor receptor
tyrosine kinase inhibitors that were isolated from cultures of the
fungus <i>Clitocybe clavipes</i>. Here, we report full details
of the total synthesis of these clavilactones. A key feature of our
synthetic approach is a ring-opening/ring-closing metathesis strategy
that allows the concise transformation of a cyclobutenecarboxylate
into a γ-butenolide. Coupled with enantioselective Ti/BINOL-catalyzed
alkynylation of a multisubstituted benzaldehyde and ring-closing metathesis
of a diene-bearing silylene acetal to construct the 10-membered carbocycle,
this strategy enabled the total synthesis of the natural enantiomers
(+)-clavilactone A and (−)-clavilactone B. In addition, the
correct structure of clavilactone D was determined by the synthesis
of two newly proposed structures. This research resulted in the asymmetric
synthesis of the revised (+)-clavilactone D