Methods for anomeric carbon-linked and fused sugar amino Acid synthesis: the gateway to artificial glycopeptides.

Glycopeptides and glycoproteins: Focus on the glycosidic linkage

Described are improved processes for the enantioselective synthesis of α-amino acids which involve combinations of solvents, highly-mixed and low-temperature reaction conditions, and novel catalysts. Also described are novel catalysts and precursors to α-amino acid derivatives.

Catalytic enantioselective synthesis of α-amino acid derivatives by phase-transfer catalysis

Deprotonation of N-protected amino acid allylic esters with LDA at −78°C and subsequent addition of a metal salt presumably results in the formation of a chelated metal enolate that undergoes Claisen rearrangement upon warming up to room temperature, giving rise to γ,δ-unsaturated amino acids. Many different metal salts can be used for chelation, but in general the best results are obtained with zinc chloride. Due to the fixed enolate geometry, as a result of chelate formation, and a strong preference for the chair-like transition state, the rearrangement proceeds with a high degree of diastereoselectivity. This method can be applied to acyclic as well as to cyclic substrates, and even to peptides, and allows the synthesis of amino acids containing quaternary carbon centers. Esters of chiral allylic alcohols produce optically active amino acids via chirality transfer from the ester moiety to the α-carbon center of the amino acid. Another possibility to introduce chirality is given by the rearrangement in the presence of chiral ligands. The best results are obtained if Al(OiPr)3 is used as the chelating metal salt and the Chinchona alkaloids as bidentate ligands. Quinine gives rise to (2R)-configured amino acids, whereas quinidine delivers the (2S) derivatives in very high yields and excellent enantioselectivities (80–93% ee). The ligands can easily be recovered nearly quantitatively from the reaction mixture.

Application of the Chelate-Enolate Claisen Rearrangement to The Synthesis of γ,δ-Unsaturated Amino Acids

Yb(OTf)3-catalyzed C-glycosylation: highly stereoselective synthesis of C-pseudoglycals

β-D-C-Allosyl-(R)-alanine 12 and β-D-C-altrosyl-(R)-alanine lactone 15 were synthesized from the common intermediate 7 in just a few steps. The β-C-glycosyloxazolone 7 was obtained in two steps from the protected D-glucal 4 by a sequential coupling with N-benzoylalanine followed by a Claisen rearrangement

Antonello Pittalis

Papers

Stereoselective synthesis of C-glycosyl .alpha.-amino acids