Synthesis of 6-azido-6-deoxy-2-n-acetyl-hexosamine-nucleoside diphosphate

A method for preparing a 6-azido-6-deoxy-1-monophosphate monosaccharide compound having structure (Va) according to the scheme:

• comprising:
• (f) converting a 6-azido-6-deoxy monosaccharide having structure (VI) in the presence of one or more Lewis acids to form an oxazoline compound having structure (VII);
• (g) reacting the oxazoline compound having structure (VII) with phosphoric acid to form the 6-azido-6-deoxy-1-monophosphate monosaccharide compound having structure (Va) or a salt thereof,
• wherein R1 and R2 are independently selected from optionally substituted C(O)-alkyl, optionally substituted C(O)-aryl and optionally substituted C(O)-arylalkyl.

A compound selected from the group consisting of:

• (i) a 6-azido-6-deoxy monosaccharide compound having structure (I):
• wherein R1 is independently selected from optionally substituted C(O)-alkyl, optionally substituted C(O)-aryl and optionally substituted C(O)-arylalkyl;
• (ii) a cyclic sulfate monosaccharide compound having structure (III):
• wherein R1 is independently selected from optionally substituted C(O)-alkyl, optionally substituted C(O)-aryl and optionally substituted C(O)-arylalkyl;
• (iii) a nucleoside diphosphate having structure (VIII):
• wherein:
• B is a nucleobase;
• R1 is independently selected from optionally substituted C(O)-alkyl, optionally substituted C(O)-aryl and optionally substituted C(O)-arylalkyl;
• R2 is selected from optionally substituted C(O)-alkyl, optionally substituted C(O)-aryl and optionally substituted C(O)-arylalkyl;
• R4 are both hydrogen or both occurrences of R4 are joined together via a carbonyl moiety;
• (iv) a 1-hydroxy-monosaccharide compound having structure (XI):
• wherein:
• R1 is selected from optionally substituted C(O)-alkyl, optionally substituted C(O)-aryl and optionally substituted C(O)-arylalkyl;
• R2 is selected from optionally substituted C(O)-alkyl, optionally substituted C(O)-aryl and optionally substituted C(O)-arylalkyl;
• (v) a phosphite having structure (XII):
• wherein:
• R1 is selected from optionally substituted C(O)-alkyl, optionally substituted C(O)-aryl and optionally substituted C(O)-arylalkyl;
• R2 is selected from optionally substituted C(O)-alkyl, optionally substituted C(O)-aryl and optionally substituted C(O)-arylalkyl;
• R3 is selected from C1-6 alkyl, allyl, 2-cyanoethyl, 2-alkylsulfonylethyl, 2-arylsulfonylethyl, 2,2,2-trichloroethyl, CH2OC(O) alkyl, fluorenylmethyl, 2-pyridylethyl, and phenyl-C1-2-alkyl, wherein the phenyl group of phenyl-C1-2-alkyl or the phenyl group of 2-arylsulfonylethyl, when 2-arylsulfonylethyl is 2-phenylsulfonylethyl, is optionally substituted with one or more halides or a nitro or methoxy group;
• (vi) a phosphate diester having structure (XIII):
• wherein:
• R1 is selected from optionally substituted C(O)-alkyl, optionally substituted C(O)-aryl and optionally substituted C(O)-arylalkyl;
• R2 is selected from optionally substituted C(O)-alkyl, optionally substituted C(O)-aryl and optionally substituted C(O)-arylalkyl;
• R3 is selected from C1-6 alkyl, allyl, 2-cyanoethyl, 2-alkylsulfonylethyl, 2-arylsulfonylethyl, 2,2,2-trichloroethyl, CH2OC(O) alkyl, fluorenylmethyl, 2-pyridylethyl, and phenyl-C1-2-alkyl, wherein the phenyl group of phenyl-C1-2-alkyl or the phenyl group of 2-arylsulfonylethyl, when 2-arylsulfonylethyl is 2-phenylsulfonylethyl, is optionally substituted with one or more halides or a nitro or methoxy group;
• (vii) an oxazoline compound having structure (VII):
• wherein R1 and R2 is independently selected from H, optionally substituted C(O)-alkyl, optionally substituted C(O)-aryl and optionally substituted C(O)-arylalkyl;
• and
• (viii) a mixture comprising the α-anomeric form and the β-anomeric form of the 6-azido-6-deoxy-1-monophosphate monosaccharide compound having structure (Va):
• wherein the molar ratio between the α-and β-anomeric form is in the range of 3/1 to 10/1, wherein both anomeric forms of compound (Va) may be in salt form, wherein R1 and R2 are independently selected from optionally substituted C(O)-alkyl, optionally substituted C(O)-aryl and optionally substituted C(O)-arylalkyl.