A preparative synthesis of 3-amino-2,3,6-trideoxy-L-lyxo-hexose (daunosamine) hydrochloride from D-mannose.
A simple, preparative route in nine steps from methyl alpha-D-mannopyranoside (1) is described that affords, in 40% overall yield, the title amino sugar 11, the sugar constituent of the antitumor antibiotics adriamycin and daunorubicin. The 2,3:4,5-dibenzylidene acetal (2) of 1 is converted by butyllithium into the 2-deoxy-3-ketone 3, whose oxime 4 is reduced with high stereoselectivity to the D-ribo amine, isolated as its N-acetyl derivative 5 and converted by action of N-bromosuccinimide into the 4-O-benzoyl-6-bromide 7. Dehydrohalogenation of  gives the 5,6-unsaturated glycoside 8, which, after O-debenzoylation to 9, undergoes stereospecific reduction by hydrogen with net C-5 inversion to give the crystalline, N-acetylated methyl beta-glycoside (10) of daunosamine, readily converted into daunosamine hydrochloride (11) and into the crystalline N-benzoyl (14) and N-acetyl(15) derivatives. No chromatographic procedures for isolation are required in any of the steps.
D003837:Deoxy Sugars / Q000138:chemical synthesis; D006595:Hexosamines / Q000138:chemical synthesis*; D008358:Mannose; D008722:Methods
D003837:Deoxy Sugars; D006595:Hexosamines; C007217:daunosamine; D008358:Mannose