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

Abstract

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.