A de novo approach to the synthesis of glycosylated methymycin analogues with structural and stereochemical diversity.

A divergent and highly stereoselective route to 11 glycosylated methymycin analogues has been developed. The key to the success of this method was the iterative use of the Pd-catalyzed glycosylation reaction and postglycosylation transformation. This unique application of Pd-catalyzed glycosylation demonstrates the breath of α/β- and d/l-glycosylation of macrolides that can be efficiently prepared using a de novo asymmetric approach to the carbohydrate portion.

Synthesis of aza-analogues of the glycosylated tyrosine portion of mannopeptimycin-E.

Two C4' amido disaccharide analogues of mannopeptimycin-E were synthesized via an iterative palladium glycosylation sequence. The stereoselective synthesis of the C4' acylated 1,4-alpha,alpha-manno,manno-amido disaccharide has been achieved in ten steps from a protected d-tyrosine. The path relies upon a regio- and diastereoselective palladium-catalyzed azide substitution reaction.

Synthetic studies toward mannopeptimycin-E: synthesis of the O-linked tyrosine 1,4-alpha,alpha-manno,manno-pyranosyl pyranoside.

[structure: see text] The enantioselective synthesis of the C-4' acylated 1,4-alpha,alpha-manno,manno-disaccharide fragment of mannopeptimycin-E has been achieved in seven steps from d-tyrosine. The route relies upon diastereoselective palladium-catalyzed glycosylation, diastereoselective reduction, and diastereoselective bis-dihydroxylation. The efficiency of the synthesis is demonstrated by the high overall yield (37%) and the preparation of various analogues.

De novo asymmetric synthesis of homoadenosine via a palladium-catalyzed N-glycosylation.

[reaction: see text] A highly stereoselective synthesis of l-2-deoxy-beta-ribo-hexopyranosyl nucleosides from 6-chloropurine and Boc-protected pyranone has been developed. Our approach relies on the iterative application of a palladium-catalyzed N-glycosylation, diastereoselective reduction, and reductive 1,3-transposition. This strategy is amenable to prepare various natural and unnatural hexopyranosyl nucleosides analogues.