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Apoptolidinone A: Synthesis of the Apoptolidin A Aglycone
Author(s) -
Schuppan Julia,
Wehlan Hermut,
Keiper Sonja,
Koert Ulrich
Publication year - 2006
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.200600461
Subject(s) - stereocenter , dihydroxylation , stereochemistry , aglycone , chemistry , aldol reaction , stereoselectivity , wittig reaction , aldehyde , acetal , organic chemistry , enantioselective synthesis , catalysis , glycoside
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.