Apoptolidinone A: synthesis of the apoptolidin A aglycone.
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.
Schuppan
Julia
J
Fachbereich Chemie, Philipps-Universität Marburg, Hans-Meerwein-Strasse, 35032 Marburg, Germany.
Wehlan
Hermut
H
Keiper
Sonja
S
Koert
Ulrich
U
D006900:Hydroxylation; D018942:Macrolides / Q000138:chemical synthesis* / Q000737:chemistry*; D011753:Pyrones / Q000138:chemical synthesis* / Q000737:chemistry*; D013237:Stereoisomerism
D018942:Macrolides; D011753:Pyrones; C506738:apoptolidin A; C504948:apoptolidinone