From Amino Acids to Fluorine-Containing Carbohydrates: De Novo Synthesis of 2-Amino-4-Fluoroxylose and -lyxose

Fluorine-containing amino sugars are highly interesting synthetic targets owing to their promising applications in medicinal chemistry. However, only a few concise approaches for their preparation are described. Herein, we wish to report on a titanium-mediated aldol addition strategy for the preparation of 2-amino-2,4-dideoxy-4-fluoropentoses. Our earlier reports on the application of serine-and threonine-derived aldehydes in this reaction are now complemented by the corresponding cysteine analogues. Furthermore, a new deprotection sequence for the fluorohydrin aldol products has been developed by applying a photochemical Pummerer-type rearrangement followed by acidic cleavage of the monothioacetals obtained, finally furnishing 2-acetamido-2,4-dideoxy-4-fluoro-D-xylose and -lyxose in a four-step synthetic sequence. Moreover, we found that the cysteine-derived aldehydes behave differently in aldol reactions compared with their serine and threonine analogues.