TY - JOUR
T1 - Total synthesis of the calphostins
T2 - Application of Fischer carbene complexes and thermodynamic control of atropisomers
AU - Merlic, C. A.
AU - Aldrich, C. C.
AU - Albaneze-Walker, J.
AU - Saghatelian, A.
AU - Mammen, J.
PY - 2001/2/23
Y1 - 2001/2/23
N2 - 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.
AB - 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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U2 - 10.1021/jo0014663
DO - 10.1021/jo0014663
M3 - Article
C2 - 11312960
AN - SCOPUS:0035936772
SN - 0022-3263
VL - 66
SP - 1297
EP - 1309
JO - Journal of Organic Chemistry
JF - Journal of Organic Chemistry
IS - 4
ER -