Synthesis of Non-NaturalO-Glycosylamino Acids Derived fromn-Pentenyl Glycosides; Model Studies and Proof of Principle for Glycopeptide Synthesis

Model studies on the transformation of the olefinic unit contained in n-pentenyl glycosides (NPGs) to glycoamino acids is described. The methodology involves a Horner-Emmons olefination with a protected glycine derived phosphonate, followed by asymmetric hydrogenation using Du-PHOS catalyst system. A variety of protecting group schemes have been investigated and their stereoselectivity in the hydrogenation reaction determined. With N-Boc and C-TSE ester protection, the diastereoselectivity in the reaction was measured by 1H NMR analysis with “racemic” product as a comparison. These modified glycoamino acids are also useful for peptide synthesis. The methodology appears to be general and was extended to include the synthesis a glycoamino acid containing the complex hexasaccharide Globo-H.