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Figure 6

reports set the foundation for subsequent studies by Yoshimura et al., who prepared several derivatives of 2-amino-2-deoxyglycuronic acids [21].

Tsuji and coworkers were the first to synthesize a 3-amino-3-deoxyhexuronic acid, in 1968 [22]. They began with an isopropylidene glucofuranosiduronic ester and introduced the nitrogen functionality via hydrazone formation and subsequent reduction. Removal of the isopropylidene resulted in formation of amino allouronic acid (Fig. 7). Paulsen and coworkers used a very similar strategy in making 3-amino-3-deoxyglucuronic acid [23].

Ogawa later published the synthesis of a 3-amino-3,4-dideoxyhexuronic acid in route to ezomycin [24]. In that account, a 1,6-anhydro epoxy sugar was reacted with sodium azide followed by antimony pentachloride to give methyl 3-azido-2-O-benzoyl-a-d-glucospyranoside. Oxidation of the primary alcohol was achieved with potassium permanganate, and reduction of the azide was accomplished with hydrogenation (Fig. 8).

Finally, in 1979 Horton reported the synthesis of 3-amino-2,3-dideoxyhexu-ronic acids. In six steps, methyl a-d-mannopyranoside was converted to a highly functionalized 3-acetamido-6-azido-2,3,6-trideoxy derivative. Photochemical activation of the azide provided an imine, which was subsequently hydrolyzed to the aldehyde. Bromine was used to oxidize the aldehyde to the acid, which was esterified with methyl iodide (Fig. 9).

In their studies directed toward the synthesis of gougerotin, Watanabe and coworkers prepared methyl-4-O-mesyl galactopyranoside and reacted it with sodium azide; after deprotection, methyl 4-azido-4-deoxyglucopyranoside was obtained [25]. This compound was oxidized with platinum and oxygen to afford the 4-azido glu-curonic acid (Fig. 10) [26]. The focus of these early synthetic studies was to prepare amino hexuronic acid derivatives that could be joined through O-glycosidic linkages, which are found in nature.

B. Syntheses of Unnatural Sugar Amino Acids

Fuchs and Lehmann demonstrated that C-glycoside amino acids could be prepared from selective ring opening of sugar-based anhydrides [27]. In the reaction, the anhydride was regioselectively reacted with ammonia to give a C-glycoside amide, which was subsequently converted to a nitrile by the action of tosyl chloride in pyridine. The nitrile was reduced with catalytic hydrogenation, and the major product resulted from migration of the C3 acetate to the C1 amine. The O- and N-acetyls were removed by saponification, using 2 N sodium hydroxide at 100°C (Fig. 11). In

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