PMID: 11312960Apr 21, 2001Paper

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

The Journal of Organic Chemistry
C A MerlicJ Mammen

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.

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Citations

Dec 8, 2005·Journal of the American Chemical Society·Yiqian Lian, William D Wulff
Nov 10, 2009·The Journal of Organic Chemistry·Carol A MulrooneyMarisa C Kozlowski
Nov 10, 2009·The Journal of Organic Chemistry·Barbara J MorganMarisa C Kozlowski
Nov 10, 2009·The Journal of Organic Chemistry·Erin M O'BrienMarisa C Kozlowski
Oct 23, 2009·Chemical Society Reviews·Marisa C KozlowskiElizabeth C Linton
Jul 1, 2012·European Journal of Organic Chemistry·Carol A MulrooeyMarisa C Kozlowski
Oct 29, 2010·Chemistry : a European Journal·Christian RinkMartin E Maier
Dec 7, 2007·Journal for the Scientific Study of Religion·Neal M Krause
Aug 24, 2005·Angewandte Chemie·Gerhard BringmannMatthias Breuning
Feb 1, 2014·Natural Product Reports·Xu-Wen Li, Bastien Nay
Oct 6, 2007·Organic Letters·Dirk SchweitzerPaul Helquist
Jun 19, 2009·Chemical Reviews·Stefan BräseCarl F Nising
Sep 30, 2010·The Journal of Organic Chemistry·Peter J ChoiMargaret A Brimble
Mar 5, 2016·Journal of the American Chemical Society·Adam G Newman, Craig A Townsend
Oct 14, 2010·Chemical Reviews·Gerhard BringmannMatthias Breuning
Dec 12, 2019·Organic Letters·Shalini VermaAkhilesh K Verma

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