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RESEARCH PRODUCT

The Allyl Ester as Carboxy-Protecting Group in the Stereoselective Construction of Neuraminic-Acid Glycosides

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The application of the allyl-ester moiety as protecting principle for the carboxy group of N-acetylneuraminic acid is described. Peracetylated allyl neuraminate 2 is synthesized by reacting the caesium salt of the acid 1 with allyl bromide. Treatment of 2 with HCl in AcCl or with HF/pyridine gives the corresponding 2-chloro or 2-fluoro derivatives 3 and 4, respectively (Scheme 1). In the presence of Ag2CO3, the 2-chloro carbohydrate 3 reacts with di-O-isopropylidene-protected galactose 5 to give the 2–6 linked disaccharide with the α-D-anomer 6a predominating (α-D/β-D = 6:1; Scheme 2). Upon activation of the 2-fluoro derivative 4 with BF3 · Et2O, the β-D-anomer 6b is formed preferentially (α-D/β-D = 1:5). In further glycosylations of 4 with long-chain alcohols, the β-D-anomers are formed exclusively (see 10 and 11; Scheme 4). The allyl-ester moiety can be removed selectively and quantitatively from the neuraminyl derivatives and the neuraminyl disaccharides by Pd(0)-catalyzed allyl transfer to morpholine as the accepting nucleophile (see Scheme 5).