2,3,4,6-Tetra-O-benzyl-D-galactose
[CAS# 53081-25-7]

Identification

• Classification: Biochemical >> Carbohydrate >> Monosaccharide
• Name: 2,3,4,6-Tetra-O-benzyl-D-galactose
• Synonyms: 2,3,4,6-Tetra-O-benzyl-D-galactopyranose
• Molecular Formula: C₃₄H₃₆O₆
• Molecular Weight: 540.65
• CAS Registry Number: 53081-25-7
• SMILES: C1=CC=C(C=C1)COC[C@H]([C@@H]([C@@H]([C@H](C=O)OCC2=CC=CC=C2)OCC3=CC=CC=C3)OCC4=CC=CC=C4)O

Properties

• Solubility: Insoluble (6.5E^-4 g/L) (25 ºC), Calc.^*
• Density: 1.179±0.06 g/cm³ (20 ºC 760 Torr), Calc.^*
• Melting point: 64 - 69 ºC (Expl.)
• Boiling point: 672.4±55.0 ºC 760 mmHg (Calc.)^*
• Flash point: 360.4±31.5 ºC (Calc.)^*
• Index of refraction: 1.619 (Calc.)^*

^* Calculated using Advanced Chemistry Development (ACD/Labs) Software.

Safety Data

• Hazard Symbols: GHS07 Warning
• Hazard Statements: H302-H315-H319-H335
• Precautionary Statements: P261-P305+P351+P338

Discovory and Applicatios

2,3,4,6-Tetra-O-benzyl-D-galactose is a selectively protected derivative of D-galactose in which the hydroxyl groups at positions 2, 3, 4, and 6 are converted into benzyl ethers, while the anomeric hydroxyl group at position 1 remains free. D-galactose was identified in the nineteenth century as a component of lactose and was recognized as an aldohexose closely related to D-glucose, differing in configuration at the C-4 position. Its cyclic pyranose structure and stereochemistry were established through classical chemical methods, including mutarotation studies and derivative formation. As carbohydrate chemistry developed in the twentieth century, methods for selective protection of hydroxyl groups became essential for controlled synthetic transformations.

The use of benzyl groups as protecting groups for alcohols was introduced into carbohydrate chemistry as part of broader advances in organic synthesis. Benzylation of hydroxyl groups is typically achieved by reaction with benzyl halides in the presence of a base, forming stable benzyl ether linkages. These ethers are resistant to a wide range of reaction conditions but can be removed by catalytic hydrogenolysis under relatively mild conditions. This combination of stability and removability made benzyl protection particularly valuable in multistep carbohydrate synthesis.

In 2,3,4,6-tetra-O-benzyl-D-galactose, four of the five hydroxyl groups of D-galactose are protected, leaving the anomeric hydroxyl group available for further reaction. The selective protection strategy is based on experimentally established procedures that control reaction conditions to achieve substitution at specific positions. By masking the secondary and primary hydroxyl groups at C-2, C-3, C-4, and C-6, chemists can direct transformations to the anomeric center, facilitating the formation of glycosidic bonds. This approach reflects a central principle of glycochemistry: the need to differentiate between multiple hydroxyl functions within a single sugar molecule.

The compound has been used as an intermediate in the synthesis of galactosides and more complex oligosaccharides. Activation of the anomeric hydroxyl group, often through conversion to a suitable leaving group, allows coupling with alcohols or other nucleophiles to form defined glycosidic linkages. After construction of the desired structure, the benzyl protecting groups can be removed by hydrogenation, regenerating the free hydroxyl groups without affecting many other functional groups. The reliability of benzyl ether cleavage under catalytic hydrogenation conditions has been well documented in the literature.

Beyond its role in glycoside synthesis, tetra-O-benzylated galactose derivatives have contributed to mechanistic studies of carbohydrate reactions. Because benzyl ethers are electronically neutral compared with acyl protecting groups, they influence reaction pathways differently. Experimental comparisons between benzylated and acetylated substrates have helped clarify how protecting groups affect stereochemical outcomes in glycosylation reactions and the stability of reaction intermediates.

The broader development of benzyl-protected sugars marked a significant advance in carbohydrate chemistry. The ability to combine orthogonal protecting groups, such as benzyl ethers and acyl esters, enabled increasingly sophisticated synthetic routes to complex glycoconjugates. Compounds like 2,3,4,6-tetra-O-benzyl-D-galactose illustrate the practical application of these strategies, grounded in reproducible experimental procedures and well-established deprotection methods.

Although 2,3,4,6-tetra-O-benzyl-D-galactose is primarily a research intermediate rather than a commercial end product, its documented preparation and use reflect the maturation of selective protection techniques in glycochemistry. Through its role in enabling controlled formation of glycosidic bonds and systematic functional group manipulation, it represents an important example of how protecting group methodology has advanced the synthesis and study of carbohydrate molecules.

References

2007. A potent bicyclic inhibitor of a family 27 alpha-galactosidase. Organic & Biomolecular Chemistry.
DOI: 10.1039/b704509c