2,3,4,6-Tetrakis-O-(phenylmethyl)-D-galactopyranose
[CAS# 6386-24-9]

Identification

• Classification: Pharmaceutical intermediate >> Heterocyclic compound intermediate >> Pyran compound
• Name: 2,3,4,6-Tetrakis-O-(phenylmethyl)-D-galactopyranose
• Synonyms: (3R,4S,5S,6R)-3,4,5-tris(phenylmethoxy)-6-(phenylmethoxymethyl)oxan-2-ol
• Molecular Formula: C₃₄H₃₆O₆
• Molecular Weight: 540.65
• CAS Registry Number: 6386-24-9
• EC Number: 826-705-0
• SMILES: C1=CC=C(C=C1)COC[C@@H]2[C@@H]([C@@H]([C@H](C(O2)O)OCC3=CC=CC=C3)OCC4=CC=CC=C4)OCC5=CC=CC=C5

Properties

• Solubility: Insoluble (2.6E^-3 g/L) (25 ºC), Calc.^*
• Density: 1.22±0.1 g/cm³ (20 ºC 760 Torr), Calc.^*
• 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: H315-H319-H335
• Precautionary Statements: P261-P264-P264+P265-P271-P280-P302+P352-P304+P340-P305+P351+P338-P319-P321-P332+P317-P337+P317-P362+P364-P403+P233-P405-P501

Discovory and Applicatios

2,3,4,6-Tetrakis-O-(phenylmethyl)-D-galactopyranose is a benzyl-protected derivative of D-galactose that has been widely used as an intermediate in carbohydrate chemistry. The compound is formed by substitution of the hydroxyl groups at the 2, 3, 4, and 6 positions of D-galactopyranose with phenylmethyl, commonly referred to as benzyl, protecting groups. The anomeric hydroxyl group at the 1 position remains free unless further derivatized. Benzyl protection of hydroxyl groups became an established strategy in the mid-twentieth century as synthetic carbohydrate chemistry developed reliable methods for selective protection and deprotection of polyhydroxylated sugars.

The introduction of benzyl groups onto D-galactose is typically achieved through treatment with benzyl halides in the presence of a base, producing ether linkages that are stable under a variety of reaction conditions. The stability of benzyl ethers toward acids and bases, combined with their ability to be removed under relatively mild hydrogenolysis conditions using catalytic hydrogenation, made them especially valuable in multistep syntheses. As carbohydrate research expanded in the 1950s and 1960s, benzyl-protected monosaccharides such as 2,3,4,6-tetrakis-O-(phenylmethyl)-D-galactopyranose became standard building blocks for the preparation of more complex oligosaccharides.

One of the principal applications of this compound has been in the stepwise construction of glycosidic linkages. In oligosaccharide synthesis, selective activation of the anomeric center allows the formation of glycosidic bonds with controlled stereochemistry. The presence of benzyl protecting groups at the secondary hydroxyl positions prevents undesired side reactions and enables chemists to direct reactivity to specific positions. Because the benzyl ether groups can be removed simultaneously by catalytic hydrogenation, they provide a practical means of global deprotection at the end of a synthetic sequence. This strategy has been used extensively in the synthesis of naturally occurring glycoconjugates, including glycoprotein fragments and glycolipids.

The compound has also played a role in methodological studies of protecting group chemistry. Comparative investigations of different protecting groups for carbohydrates have consistently evaluated benzyl ethers because of their chemical robustness and compatibility with a wide range of reagents. 2,3,4,6-Tetrakis-O-(phenylmethyl)-D-galactopyranose serves as a representative substrate for examining regioselective reactions at the anomeric hydroxyl group and for testing conditions for selective deprotection. The benzyl groups shield the secondary hydroxyls while leaving the hemiacetal functionality accessible for conversion into glycosyl donors such as halides, trichloroacetimidates, or thioglycosides, which are well-established intermediates in glycosylation chemistry.

In addition to its use in synthetic assembly, the compound has been employed in structural and conformational studies of protected sugars. Spectroscopic analyses, including nuclear magnetic resonance measurements, have been carried out on benzylated galactopyranose derivatives to understand conformational preferences of the pyranose ring and the influence of protecting groups on stereochemical outcomes. Such studies have contributed to the broader understanding of carbohydrate reactivity and stereocontrol in glycoside formation.

The historical development of protected monosaccharide intermediates, including 2,3,4,6-tetrakis-O-(phenylmethyl)-D-galactopyranose, reflects the maturation of carbohydrate chemistry into a precise and predictable synthetic discipline. By enabling selective manipulation of individual hydroxyl groups, benzyl protection strategies have supported the preparation of defined oligosaccharides for biological research. These synthetic advances have facilitated investigations into cell-surface recognition, antigen structure, and carbohydrate-protein interactions, where well-defined galactose-containing structures are required. As a result, this benzylated galactose derivative remains a documented and practical intermediate in laboratory-scale carbohydrate synthesis.

References

2015. Divergent Synthesis of Aminocyclopentitol Analogues via Stereoselective Amination of Cyclic Polybenzyl Ether with Chlorosulfonyl Isocyanate. Synlett.
DOI: 10.1055/s-0034-1380227