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Apoptolidin A: Total Synthesis and Partially Glycosylated Analogues
Author(s) -
Wehlan Hermut,
Dauber Mario,
Fernaud M. Teresa Mujica,
Schuppan Julia,
Keiper Sonja,
Mahrwald Rainer,
Garcia M.Elisa Juarez,
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.200600462
Subject(s) - total synthesis , chemistry , glycosylation , stereochemistry , computational biology , biology , biochemistry
The total synthesis of apoptolidin A is described employing an early glycosylation strategy. Strategic disconnections were chosen between C11–C12 (cross‐coupling) and C19O–C1 (macrocyclization). The cis ‐selective glycosylation at C9‐OH was achieved with the new SIBA protective group at O2/O3 of the L ‐glucose residue. Auxiliary substitutents at the 2‐position of the 2‐deoxy sugars were applied to form selectively the glycosidic linkages of the C27 disaccharide. The cross‐coupling of the glycosylated northern half with the glycosylated southern half was achieved with Cu I ‐thiophene carboxylate. The macrocyclization of a trihydroxy carboxylic acid produced the 20‐membered macrolide selectively. H 2 SiF 6 was suitable for the final deprotection of the silyl ethers and the conversion of the C21 methylketal into the hemiketal. The synthetic flexibility of the approach was proven by the synthesis of some glycovariants.