A method for the installation of the (2-thiazolylcarbonyl)methylene group, i.e. a masked pyruvate unit owing to the thiazole to formyl equivalence, in sugar-derived aldehydes has been developed. The strategy involves stereoselective carbon-carbon and carbon-oxygen bond formation, the former consisting of a Wittig olefination with a thiazole-armed carbonyl ylid, the latter involving a conjugate addition of the benzyl oxide anion to the resultant E α,β-enone. This addition was mainly anti (ds 78-85%) to a resident γ-benzyloxy group in the enone, but changed to syn (ds 70-95 %) with a chiral 1, 3-dioxolane or 1, 3-dioxane ring. The removal of the hydroxy-protecting groups and the consequent cyclization via intramolecular ketalization gave 2-thiazolyl-substituted pyranoses at C-1. The unmasking of the formyl group from the thiazole ring in these compounds afforded 3-deoxy-2-aldopyranosuloses, which were quantitatively oxidized to pyranosulonic acids. Applications of this strategy to the total synthesis of DAH (D-arabino-heptulosonic), KDN (D-glycero-D-galacfo-nonulosonic), and its D-glycero-o-talo epimer, 4-epi-KDN, are described.© 1994, American Chemical Society. All rights reserved.
Installation of the Pyruvate Unit in Glycidic Aldehydes via a Wittig Olefination-Michael Addition Sequence Utilizing a Thiazole-Armed Carbonyl Ylide. A New Stereoselective Route to 3-Deoxy-2-Ulosonic Acids and the Total Synthesis of DAH, KDN, and 4-epi-KDN
DONDONI, Alessandro;MARRA, Alberto;
1994
Abstract
A method for the installation of the (2-thiazolylcarbonyl)methylene group, i.e. a masked pyruvate unit owing to the thiazole to formyl equivalence, in sugar-derived aldehydes has been developed. The strategy involves stereoselective carbon-carbon and carbon-oxygen bond formation, the former consisting of a Wittig olefination with a thiazole-armed carbonyl ylid, the latter involving a conjugate addition of the benzyl oxide anion to the resultant E α,β-enone. This addition was mainly anti (ds 78-85%) to a resident γ-benzyloxy group in the enone, but changed to syn (ds 70-95 %) with a chiral 1, 3-dioxolane or 1, 3-dioxane ring. The removal of the hydroxy-protecting groups and the consequent cyclization via intramolecular ketalization gave 2-thiazolyl-substituted pyranoses at C-1. The unmasking of the formyl group from the thiazole ring in these compounds afforded 3-deoxy-2-aldopyranosuloses, which were quantitatively oxidized to pyranosulonic acids. Applications of this strategy to the total synthesis of DAH (D-arabino-heptulosonic), KDN (D-glycero-D-galacfo-nonulosonic), and its D-glycero-o-talo epimer, 4-epi-KDN, are described.© 1994, American Chemical Society. All rights reserved.I documenti in SFERA sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
