1,2-O-Isopropylidene-alpha-D-xylofuranose
[CAS# 20031-21-4]

Identification

• Classification: Biochemical >> Carbohydrate >> Monosaccharide
• Name: 1,2-O-Isopropylidene-alpha-D-xylofuranose
• Molecular Formula: C₈H₁₄O₅
• Molecular Weight: 190.19
• CAS Registry Number: 20031-21-4
• EC Number: 606-426-9
• SMILES: CC1(O[C@@H]2[C@H]([C@H](O[C@@H]2O1)CO)O)C

Properties

• Density: 1.3±0.1 g/cm³ Calc.^*
• Melting point: 69 - 71 ºC (Expl.)
• Boiling point: 333.0±37.0 ºC 760 mmHg (Calc.)^*, 443.5 - 447.1 ºC (Expl.)
• Flash point: 155.2±26.5 ºC (Calc.)^*
• Index of refraction: 1.486 (Calc.)^*
• Alpha: -19.2 º (c=1 in H2O) (Expl.)

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

Safety Data

• Hazard Symbols: GHS07 Warning
• Hazard Statements: H302-H315-H319-H335
• Precautionary Statements: P261-P264-P264+P265-P270-P271-P280-P301+P317-P302+P352-P304+P340-P305+P351+P338-P319-P321-P330-P332+P317-P337+P317-P362+P364-P403+P233-P405-P501

Hazard Classification

Hazard	Class	Category Code	Hazard Statement
Eye irritation	Eye Irrit.	2A	H319
Skin irritation	Skin Irrit.	2	H315
Specific target organ toxicity - single exposure	STOT SE	3	H335

Discovory and Applicatios

1,2-O-Isopropylidene-α-D-xylofuranose is a protected derivative of D-xylose in which the hydroxyl groups at the 1- and 2-positions are linked through an isopropylidene acetal. The compound is formed by treatment of D-xylose with acetone in the presence of an acid catalyst, resulting in ketal formation between acetone and the vicinal diol at C-1 and C-2. This reaction stabilizes the five-membered furanose form of the sugar and produces a crystalline intermediate widely used in carbohydrate synthesis.

The development of acetonide protection arose from early 20th-century efforts to control the reactivity of polyhydroxy compounds. Once the stereochemistry of aldopentoses such as D-xylose had been established, chemists recognized that selective functionalization required temporary masking of specific hydroxyl groups. Formation of cyclic acetals with acetone proved to be an effective method for protecting adjacent hydroxyls while leaving other positions available for reaction. The 1,2-O-isopropylidene derivative became a standard intermediate because it blocks both the anomeric hydroxyl group and the neighboring secondary hydroxyl group in a single transformation.

Structural characterization of 1,2-O-isopropylidene-α-D-xylofuranose has been achieved through established analytical methods. Optical rotation measurements confirm retention of the D-configuration and the alpha orientation at the anomeric center. Infrared spectroscopy shows characteristic absorptions corresponding to acetal linkages, while nuclear magnetic resonance spectroscopy provides detailed information about substitution patterns and ring conformation. These experimental techniques collectively verify the presence of the isopropylidene group and the furanose ring structure.

The compound has been widely used as a synthetic intermediate because protection at the 1,2-positions allows selective modification of the remaining hydroxyl groups at C-3 and C-5. Transformations such as esterification, etherification, oxidation, or substitution can be performed at these unprotected positions with improved regioselectivity. After completion of the desired reactions, the isopropylidene group can be removed under controlled acidic conditions, regenerating the original diol without altering other functionalities introduced during synthesis.

In nucleoside and carbohydrate chemistry, protected pentose derivatives like 1,2-O-isopropylidene-α-D-xylofuranose have served as building blocks for the preparation of glycosides and related compounds. By stabilizing the furanose form and controlling the reactivity of the anomeric center, chemists can carry out stepwise synthesis of more complex structures. Such methods have been documented in studies aimed at preparing modified sugars and biologically relevant analogues.

The isopropylidene group also influences the conformational properties of the sugar ring. Investigations of related acetonide-protected pentoses using crystallographic and spectroscopic techniques have demonstrated that cyclic acetal formation imposes defined torsion angles and affects ring puckering. These structural constraints can alter reactivity and selectivity in subsequent reactions, providing insight into structure–reactivity relationships in carbohydrate chemistry.

The introduction of isopropylidene protection marked an important advance because it offers a balance between stability and reversibility. The acetal linkage withstands neutral and mildly basic conditions but can be cleaved under aqueous acidic conditions without disrupting the carbon framework of the sugar. This property has made 1,2-O-isopropylidene-α-D-xylofuranose a reliable intermediate in multistep synthetic sequences.

Through its preparation, structural verification, and practical application in regioselective transformations, 1,2-O-Isopropylidene-α-D-xylofuranose exemplifies the established methodology of protecting group chemistry in pentose sugar research. Its use is supported by well-documented experimental studies in organic and carbohydrate chemistry.

References

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2021. Synthesis of a Key Subunit of HIV-1 Protease Inhibitor Darunavir. Synfacts.
DOI: 10.1055/s-0040-1719792

2019. Synthesis of a cGAMP Analogue. Synfacts.
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2016. Synthesis, characterization and antimicrobial activity of novel Schiff base tethered boronate esters of 1,2-O-isopropylidene-a-d-xylofuranose. Bioorganic & Medicinal Chemistry Letters.
DOI: 10.1016/j.bmcl.2016.06.049

2011. Efficient synthesis, structural characterization and anti-microbial activity of chiral aryl boronate esters of 1,2-O-isopropylidene-a-d-xylofuranose. Bioorganic & Medicinal Chemistry Letters.
DOI: 10.1016/j.bmcl.2011.05.036

2011. Metal-Free Deprotection of Terminal Acetonides by Using tert-Butyl Hydroperoxide in Aqueous Medium. Synlett.
DOI: 10.1055/s-0030-1259917