Synthetic Routes towards Fluorine-Containing Amino Sugars: Synthesis of Fluorinated Analogues of Tomosamine and 4-Amino-4-deoxyarabinose

Fluorinated analogues of bioactive amino sugars are of high interest in medicinal chemistry. We developed a straightforward synthetic route towards this class of carbohydrates by applying a titanium‐mediated aldol addition. Thus, two‐carbon chain elongations of serine‐ and threonine‐derived aldehydes with a chiral fluoroacetyl‐oxazolidinone could be achieved in good yields and excellent diastereoselectivities to generate a fluorohydrin‐containing carbon skeleton. A short deprotection sequence subsequently furnished the pyranoid forms of various 4‐amino‐2‐fluoropentoses and ‐hexoses, respectively. The versatility of this strategy was demonstrated by the stereoselective synthesis of naturally abundant 4‐amino‐4‐deoxyarabinose and 4‐amino‐4,6‐dideoxygalactose (tomosamine). 4‐Amino‐2‐fluoropentoses and ‐hexoses were prepared through two‐carbon chain elongations by Ti‐mediated aldol additions of serine‐ and threonine‐derived amino aldehydes to fluoroacetyl‐ephedrine‐oxazolidinone. Excellent stereoselectivities were attained for matched‐case fluorohydrins, which were deprotected in a short sequence.