Format

Send to

Choose Destination
J Org Chem. 2001 Feb 23;66(4):1297-309.

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

Author information

1
Department of Chemistry and Biochemistry, University of California, Los Angeles, California 90095-1569, USA. merlic@chem.ucla.edu

Abstract

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.

PMID:
11312960
DOI:
10.1021/jo0014663
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for American Chemical Society
Loading ...
Support Center