Toward Bis C,C‐Glycosyl Compounds and Anomeric γ‐Glycoamino Acids through Michael Addition Reaction of Nitromethane on Z/E Push‐Pull Sugar Olefins

Abstract

The nucleophilic addition of a nitronate anion on push-pull anomeric sugar olefins has been studied and the results reveal that this reaction opens a new and efficient access to anomeric γ-nitro esters when applied to furanoglycosylidenes. The 1,4-addition reaction occurs mainly from the lesscrowded face, i.e. the opposite side to the 4,5-isopropylidene protecting group. Very different reactivities for E and Z isomers were observed and this experimental finding was rationalized on the basis of quantum mechanical calculations.[a]

Sugar γ‐Amino Acids as Building Blocks for the Synthesis of Cyclic Neoglycopeptides.

“…The nucleophilic addition of a nitronate anion on push‐pull anomeric sugar olefins has been previously studied in our group (Scheme ) . Michael adducts 1 were obtained in excellent yield as a mixture of inseparable nitro esters starting from the corresponding erythro‐glycosylidene (14/86:α/β ratio), the major anomer bearing the nitro group on the less hindered face of the sugar.…”

“…Once the nitro group is reduced to an amino group and protected, this opening/closing process was never observed and no epimerization occurred. The configuration of the major anomer (methyl carboxylate and isopropylidene on the same face) was established on the basis of 1 H NMR spectroscopic data by NOESY experiments on α/β mixture and X‐ray crystallographic analysis . Anomeric mixture of nitro esters 1 was treated with lithium hydroxide in THF/H 2 O to give the corresponding carboxylic acid in very good yield.…”

“…The selective removal of the 7,8‐ O ‐isopropylidene protecting group was achieved by treatment with 1 N HCl in MeOH. The corresponding diol was obtained as a mixture of anomers and separated by column chromatography . We decided to go ahead with the major isomer 10 and oxidative cleavage of the diol followed by reduction of the aldehyde intermediate led to compound 12 bearing a hydroxymethyl arm.…”

“…However, compound 11 was obtained in only 15% yield after addition of nitromethane anion. We previously showed that both anomers are in equilibrium in the reaction medium likely via opening and closure of the sugar ring, thus precluding the formation of 11 in better yield . A multistep synthesis starting from this minor anomer is not a reasonable option and the successful synthesis of cyclopeptides requires the use of major β‐anomers.…”

“…As unusual amino acids with multiple functionalization points, sugar amino acids are good candidates and can be incorporated into peptidic structures. A few years ago, we developed anomeric sugar β‐ and γ‐amino acids and we integrated them into small mixed peptides,, and cyclic glycopeptides, displaying specific conformational properties.…”