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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)
 
 
 

Total synthesis of the calphostins: application of fischer carbene complexes and thermodynamic control of atropisomers.

The total syntheses of the potent protein kinase C inhibitors calphostins A, B, C, and D as well as a variety of structural analogues are reported. An aminobenzannulation reaction of an enantiopure chromium Fischer carbene complex is utilized to prepare a pentasubstituted naphthylamine. After optimization of side-chain substituents, conversion of the naphthylamine to an o-naphthoquinone was followed by biomimetic oxidative dimerization using trifluoroacetic acid and air yielding a 1:2 P/M mixture of atropisomeric perylenequinones. Thermal equilibration to a 3:1 P:M atropisomeric ratio and separation of the perylenequinones followed by side chain desymmetrization and functionalization led to the total synthesis of enantio- and diastereomerically pure calphostin C in only twelve steps from commercially available starting materials. In addition, calphostins A, B, D, and several structural analogues were prepared to evaluate biological activities.[1]

References

  1. Total synthesis of the calphostins: application of fischer carbene complexes and thermodynamic control of atropisomers. Merlic, C.A., Aldrich, C.C., Albaneze-Walker, J., Saghatelian, A., Mammen, J. J. Org. Chem. (2001) [Pubmed]
 
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