title: Apoptolidin A: total synthesis and partially glycosylated analogues.
abstract: 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 CuI-thiophene carboxylate. The macrocyclization of a trihydroxy carboxylic acid produced the 20-membered macrolide selectively. H2SiF6 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.
authors.affiliation: Fachbereich Chemie, Philipps-Universität Marburg, Hans-Meerwein-Strasse, 35032 Marburg, Germany.
authors.forename: Hermut
authors.initials: H
authors.lastname: Wehlan
authors.forename: Mario
authors.initials: M
authors.lastname: Dauber
authors.forename: M Teresa Mujica
authors.initials: MT
authors.lastname: Fernaud
authors.forename: Julia
authors.initials: J
authors.lastname: Schuppan
authors.forename: Sonja
authors.initials: S
authors.lastname: Keiper
authors.forename: Rainer
authors.initials: R
authors.lastname: Mahrwald
authors.forename: M-Elisa Juarez
authors.initials: ME
authors.lastname: Garcia
authors.forename: Ulrich
authors.initials: U
authors.lastname: Koert
mesh_terms: D006001:Glycoconjugates / Q000138:chemical synthesis / Q000737:chemistry; D006027:Glycosides / Q000737:chemistry; D006031:Glycosylation; D018942:Macrolides / Q000138:chemical synthesis* / Q000737:chemistry*; D011753:Pyrones / Q000138:chemical synthesis* / Q000737:chemistry*
chemical_list: D006001:Glycoconjugates; D006027:Glycosides; D018942:Macrolides; D011753:Pyrones; C506738:apoptolidin A