Apoptolidin A: total synthesis and partially glycosylated analogues.
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.
Wehlan
Hermut
H
Fachbereich Chemie, Philipps-Universität Marburg, Hans-Meerwein-Strasse, 35032 Marburg, Germany.
Dauber
Mario
M
Fernaud
M Teresa Mujica
MT
Schuppan
Julia
J
Keiper
Sonja
S
Mahrwald
Rainer
R
Garcia
M-Elisa Juarez
ME
Koert
Ulrich
U
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*
D006001:Glycoconjugates; D006027:Glycosides; D018942:Macrolides; D011753:Pyrones; C506738:apoptolidin A