Patent ID: 7288640
Filing Date: 2007-10-30
Classification: C07H

Abstract:
1. A method for preparing an aminoalkyl glucosaminide 4-phosphate compound having the formula: wherein X is Y is —O— or —NH—; R comprising: (a) selectively 6-O-silylating a 2-amino-2-deoxy-β-D-glucopyranose derivative having the formula: wherein X is O or S; and PG independently represents a protecting group that forms an ester, an ether or a carbonate with the oxygen atom of a hydroxy group or that forms an amide or a carbamate with the nitrogen atom of an amino group, respectively; with a trisubstituted chlorosilane R (b) selectively acylating the 4-OH position of the resulting 6-O-silylated derivative with an (R)-3-alkanoyloxyalkanoic acid or a hydroxy-protected (R)-3-hydroxyalkanoic acid in the presence of a carbodiimide reagent and catalytic 4-dimethylaminopyridine or 4-pyrrolidinopyridine to give a 4-O-acylated derivative; (c) selectively deprotecting the nitrogen protecting groups, sequentially or simultaneously, and N,N-diacylating the resulting diamine with an (R)-3-alkanoyloxyalkanoic acid or a hydroxy-protected (R)-3-hydroxyalkanoic acid in the presence of a peptide coupling reagent; (d) introducing a protected phosphate group at the 4-position with a chlorophosphate or phosphoramidite reagent to give a phosphotriester; and (e) simultaneously or sequentially deprotecting the phosphate, silyl, and remaining protecting groups.