反应详情

Alternatively, 3,4,5-trihydroxy-6-{2-methyl-2-[3-(3-{4-[7-(2-morpholin-4-yl-ethoxy)-benzo[d]imidazo[2,1-b]thiazol-2-yl]-phenyl}-ureido)-isoxazol-5-yl]-propoxy}-tetrahydro-pyran-2-carboxylic acid (I-6) is prepared by following an alternative general procedure given in Org. Lett. 2008, 10, 1585. To a stirred mixture of 1-[5-(2-hydroxy-1,1-dimethyl-ethyl)-isoxazol-3-yl]-3-{4-[7-(2-morpholin-4-yl-ethoxy)-benzo[d]imidazo[2,1-b]thiazol-2-yl]-phenyl}-urea (I-1) (1 equivalent) in a mixture of dimethyl sulfoxide (final volume 12.5-25% v/v) and 50 mM sodium phosphate buffer (pH=7.5) at rt, is added a solution of 1-deoxy-1-fluoro-α-D-glucopyranuronic acid ammonium salt (prepared as described in Org. Lett. 2008, 10, 1585) (1.2 equivalents) in 50 mM sodium phosphate buffer (pH=7.5). To this mixture is added E. coli. E504G β-glucuronylsynthase (final concentration 0.1-0.2 mg/mL) or E. coli. E504A β-glucuronylsynthase (final concentration 0.1-0.2 mg/mL) and the mixture is stirred at rt for 4 days. Lyophilization of the mixture and purification of the residue by preparative reverse-phase HPLC or silica gel flash chromatography affords 3,4,5-trihydroxy-6-{2-methyl-2-[3-(3-{4-[7-(2-morpholin-4-yl-ethoxy)-benzo[d]imidazo[2,1-b]thiazol-2-yl]-phenyl}-ureido)-isoxazol-5-yl]-propoxy}-tetrahydro-pyran-2-carboxylic acid (I-6).

1. customAlternatively, 3,4,5-trihydroxy-6-{2-methyl-2-[3-(3-{4-[7-(2-morpholin-4-yl-ethoxy)-benzo[d]imidazo[2,1-b]thiazol-2-yl]-phenyl}-ureido)-isoxazol-5-yl]-propoxy}-tetrahydro-pyran-2-carboxylic acid (I-6) is prepared
2. additionTo this mixture is added E
3. customLyophilization of the mixture and purification of the residue by preparative reverse-phase HPLC or silica gel flash chromatography