Synthesis of the Hydroxyamino Sugar of Calicheamicins
Methyl 6-deoxy-2,3-O-isopropylidene-4-O-mesyl-α-D-galactopyranoside (6) was prepared from D-galactose in six steps. 6 was subjected to a nucleophilic displacement reaction with sodium azide as the nucleophile to yield methyl 4-azido-4,6-dideoxy-2,3-O-isopropylidene-α-D-glucopyranoside (7) in 75% yield. Reduction of the azido group with NaBH4 afforded the amino sugar 8 (81%) which was adsorbed on silica gel and subsequently oxidized with ozone to methyl 4,6-dideoxy-2,3-O-isopropylidene-4-nitro-α-D-glucopyranoside (10, 80%). This crystalline and stable compound 10 was reduced with Zn/NH4Cl to yield the desired methyl 4,6-dideoxy-4-hydroxy-amino-2,3-O-isopropylidene-α-D-glucopyranoside (11, 85%), which is unstable to air and therefore has to be transferred to its N,O-diacetate derivate 12. No chromatographic purification was necessary.