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).