Methyl 5-acetamido-4,7,8,9-tetra-O-acetyl-2,6-anhydro-3,5-Dideoxy-D-glycero-d-galacto-non-2-enonate

• CAS: 73960-72-2
• Catalog Number: ACM73960722
• Category: Main Products
• Molecular Weight: 473.43
• Molecular Formula: C₂₀H₂₇NO₁₂
• Synonyms: 5-(Acetylamino)-3,5-dideoxy-D-glycero-|A-D-galacto-2-nonulopyranosonic AcidMethyl Ester; methyl 5-acetamido-4,7,8,9-tetra-O-acetyl-2,3,5-trideoxy-D-glycero-D-galacto-non-2-enopyranosonate; methyl 5-acetamido-4,7,8,9-tetra-O-acetyl-3,5-dideoxy-2,6-anhydro-D-glycero-D-galacto-non-2-enonate; methyl 5-acetamido-4,7,8,9-tetra-O-acetyl-2,6-anhydro-3,5-dideoxy-D-glycero-D-galacto-non-2-enoate; P906; methyl 5-acetamido-3,5-dideoxy-D-glycero-D-galacto-2-nonulopyranosonate; N-Acetylneuraminic acid methyl ester; methyl 5-acetdmino-4,7,8,9-tetra-O-acetyl-2,6-anhydro-3,5-dideoxy-D-glycero-D-galacto-non-2-enolate; (2S,4S,5R,6R)-methyl 5-acetamido-2,4-dihydroxy-6-((1R,2R)-1,2,3-trihydroxypropyl)tetrahydro-2H-pyran-2-carboxylate; methyl 5-acetamido-4,7,8,9-tetra-O-acetyl-2,6-anhydro-3,5,9-trideoxy-D-glycero-D-galacto-non-2-enoate
• IUPAC Name: methyl(2R,3R,4S)-3-acetamido-4-acetyloxy-2-[(1S,2R)-1,2,3-triacetyloxypropyl]-3,4-dihydro-2H-pyran-6-carboxylate
• SMILES: CC(=O)NC1C(C=C(OC1C(C(COC(=O)C)OC(=O)C)OC(=O)C)C(=O)OC)OC(=O)C
• InChI Key: UZTLYEOULACYKZ-AIHBUXEESA-N
• Boiling Point: 571.8ºC at 760 mmHg
• Melting Point: 126-127ºC
• Density: 1.31g/cm³
• Appearance: Pale Yellow Solid
• Exact Mass: 473.15300

Case Study

Methyl 5-Acetamido-4,7,8,9-tetra-O-acetyl-2,6-anhydro-3,5-dideoxy-D-glycero-D-galacto-non-2-enonate as a Key Intermediate for 4-Azido Sialic Acid Synthesis

Gray, Taylor E., et al. RSC Chemical Biology 6.6 (2025): 869-881.

This peracetylated sialic acid derivative is a crucial precursor for introducing an azide group at the C4 position of N-acetylneuraminic acid (Neu5Ac). It enables the preparation of 4-azido sialic acid for metabolic oligosaccharide engineering and glycan-binding protein studies.
Synthesis: Treatment of the title compound (1) with TMSOTf in ethyl acetate at 50 °C gave the oxazoline derivative (2) in 75 % yield. The oxazoline was then opened with TMSN3 in refluxing tBuOH to install the azide stereoselectively at C4, affording the 4-azido unsaturated derivative (3) in 83 % yield. This compound was further elaborated via bromohydroxylation and radical debromination to the fully protected 4-azido Neu5Ac (6).
Performance Evaluation: The key intermediate (2) was characterized by ¹H and ¹³C NMR and HRMS. The overall route provided access to peracetylated 4-azido Neu5Ac (6) with good efficiency, overcoming previous difficulties with direct azide substitution. The final deprotected 4-azido sialic acid (11) was obtained by a thio-glycoside protection strategy to avoid alkaline degradation. Metabolic incorporation studies in U937 cells showed that peracetylated 4-azido Neu5Ac (6) was incorporated into cell surface glycans nearly as efficiently as the standard Neu5Az, with only a 21 % lower signal at the highest dose.
Conclusion: This sialic acid derivative serves as a versatile building block for synthesizing C4-modified sialosides, enabling alternative bioorthogonal labeling and the study of sialic acid-binding proteins such as Siglec-7.