Application to aminoglycosides bearing basic nitrogen 8)Although aminosugars are present in ~40% of glycosylated bacterial metabolites9), to date, there are no general methods for the synthesis of aminoglycosides; instead such reactions are often optimized on a case-by-case basis. The amine Figure 1. Umpolung glycosylation general reaction scheme and representative substrate scopean alkyl 2-(2-methyltetrahydropyranyl)peroxide (MTHP peroxide) to a configurationally-defined anomeric anion intermediate. This work was based on pioneering studies of Rychnovsky4) and Cohen5), who established that configurationally-defined 2-lithiotetrahydopyranyl anions could be generated by reductive lithiation of α-alkoxythiophenyl ethers, and work from Dussault and co-workers6), who advanced alkyl 2-tetrahydropyranyl peroxides as synthetically-useful alkoxenium ion equivalents. Additionally, a closely related approach to S-glycosides by Zhu and co-workers provided important precedent for our studies7). The configuration of the anomeric anion can be thermally-controlled, allowing access to α- or β-2-deoxyglycosides from a single starting thioglycoside. Representative products are shown in Figure 1. The reaction is compatible with a range of 2-deoxyglycosyl donors and primary and secondary peroxide electrophiles. Figure 2. Selected applications of the umpolung glycosylation to aminosugarsfunctionality hinders electrophilic activation of the anomeric center due to competitive coordination to the basic amine. Protection of the amine with an electron withdrawing group can alleviate this issue, but the resulting carbohydrate is less 103
元のページ ../index.html#103