Apoptolidinone A: Synthesis of the Apoptolidin A Aglycone
Julia Schuppan Dr.
Fachbereich Chemie, Philipps-Universität Marburg Hans-Meerwein-Strasse, 35032 Marburg, Germany, Fax: (+49) 6421-282-5677
Search for more papers by this authorHermut Wehlan Dr.
Fachbereich Chemie, Philipps-Universität Marburg Hans-Meerwein-Strasse, 35032 Marburg, Germany, Fax: (+49) 6421-282-5677
Search for more papers by this authorSonja Keiper Dr.
Fachbereich Chemie, Philipps-Universität Marburg Hans-Meerwein-Strasse, 35032 Marburg, Germany, Fax: (+49) 6421-282-5677
Search for more papers by this authorUlrich Koert Prof. Dr.
Fachbereich Chemie, Philipps-Universität Marburg Hans-Meerwein-Strasse, 35032 Marburg, Germany, Fax: (+49) 6421-282-5677
Search for more papers by this authorJulia Schuppan Dr.
Fachbereich Chemie, Philipps-Universität Marburg Hans-Meerwein-Strasse, 35032 Marburg, Germany, Fax: (+49) 6421-282-5677
Search for more papers by this authorHermut Wehlan Dr.
Fachbereich Chemie, Philipps-Universität Marburg Hans-Meerwein-Strasse, 35032 Marburg, Germany, Fax: (+49) 6421-282-5677
Search for more papers by this authorSonja Keiper Dr.
Fachbereich Chemie, Philipps-Universität Marburg Hans-Meerwein-Strasse, 35032 Marburg, Germany, Fax: (+49) 6421-282-5677
Search for more papers by this authorUlrich Koert Prof. Dr.
Fachbereich Chemie, Philipps-Universität Marburg Hans-Meerwein-Strasse, 35032 Marburg, Germany, Fax: (+49) 6421-282-5677
Search for more papers by this authorGraphical Abstract
An efficient synthesis of apoptolidinone A using a CuI-mediated cross-coupling key step is described. Key steps for the introduction of the southern half stereocenters are a stereoselective aldol reaction, a substrate controlled dihydroxylation and a chelation-controlled Grignard/aldehyde addition. The conjugated triene of the northern half was built up successively by E-selective Wittig reactions.
Abstract
An efficient stereocontrolled synthesis of apoptolidinone A, the aglycone of apoptolidin A is described. The synthetic strategy relies on a cross coupling between C11/C12 of a northern half (C1–C11) and a southern part (C12–C28) followed by a ring-size selective macrolactonization. Key steps for the introduction of the southern half stereocenters are a stereoselective aldol reaction, a substrate controlled dihydroxylation and a chelation-controlled Grignard/aldehyde addition. The conjugated triene of the northern half was built up successively by E-selective Wittig reactions. L-Malic acid was chosen as the chiral pool source for the C8/C9 stereocenters. The final cleavage of the silyl ethers and the conversion of the C21 methyl ketal into the hemiketal was achieved by HF⋅pyridine.
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