Chlorosulphation of amino sugars: synthesis of methyl 2-acetamido-4-amino-2,4,6-trideoxy-β-D-glucopyranoside (bacillosamine) from a D-glucosamine derivative

Abstract

Chlorosulphation of methyl 2-deoxy-2-phthalimido-β-D-glucopyranoside 3 under controlled conditions provided either methyl 6-chloro-2,6-dideoxy-2-phthalimido-β-D-glucopyranoside 4 or methyl 4,6-dichloro-2,4,6-trideoxy-2-phthalimido-β-D-galactopyranoside 5. Chlorination at C-4 occurs to the exclusion of that at C-3, in sharp contrast to the chlorosulphation of methyl β-D-glucopyranoside which is known to give both the 4,6-dichloro-galacto- and 3,6-dichloro-allo-pyranosides. Conversion of the chlorinated phthalimido derivatives 4 and 5 to the corresponding 2-acetamido-2-deoxyhexopyranosides 6 and 7 permitted reduction of the chloro functions by palladium, W-4 Raney nickel, and nickel boride. Reduction of methyl 2-acetamido-6-chloro-2,6-dideoxy-β-D-glucopyranoside 6 by Raney nickel gave methyl 2-acetamido-2,6-dideoxy-β-D-glucopyranoside 8. Selective dechlorination at C-4 was achieved by palladium catalysed reduction of methyl 2-acetamido-4,6-dichloro-2,4,6-trideoxy-β-D-galactopyranoside 7. Nickel boride or Raney nickel reduction of 7 effected selective dechlorination at C-6 to give methyl 2-acetamido-4-chloro-2,4,6-trideoxy-β-D-galactopyranoside 9. Azide displacement of the 4-chloro group of 9 provided a simple route to the 2,4-diamino sugar bacillosamine. A side product of the azide displacement reaction was the unsaturated sugar, methyl 2-acetamido-2,4,6-trideoxy-α-L-threo-hex-4-enopyranoside, 14.