Methyl (R)-(-)-3-hydroxybutyrate
[CAS# 3976-69-0]

Identification

• Classification: Chemical reagent >> Organic reagent >> Fatty acid
• Name: Methyl (R)-(-)-3-hydroxybutyrate
• Synonyms: methyl (3R)-3-hydroxybutanoate
• Molecular Formula: C₅H₁₀O₃
• Molecular Weight: 118.13
• CAS Registry Number: 3976-69-0
• EC Number: 223-610-0
• SMILES: C[C@H](CC(=O)OC)O

Properties

• Density: 1.1±0.1 g/cm³ Calc.^*, 1.055 g/mL (Expl.)
• Boiling point: 161.9 °C 760 mmHg (Calc.)^*, 188.3 - 191.1 °C (Expl.)
• Flash point: 71.7 °C (Calc.)^*, 73 °C (Expl.)
• Index of refraction: 1.42 (Calc.)^*, 1.422 (Expl.)
• Alpha: -21.5 ° (neat) (Expl.)

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

Safety Data

• Hazard Symbols: GHS05;GHS07 Danger
• Risk Statements: H315-H318-H319-H335
• Safety Statements: P261-P264-P264+P265-P271-P280-P302+P352-P304+P340-P305+P351+P338-P305+P354+P338-P317-P319-P321-P332+P317-P337+P317-P362+P364-P403+P233-P405-P501

Hazard Classification

Hazard	Class	Category Code	Hazard Statement
Skin irritation	Skin Irrit.	2	H315
Specific target organ toxicity - single exposure	STOT SE	3	H335
Eye irritation	Eye Irrit.	2	H319
Serious eye damage	Eye Dam.	1	H318
Eye irritation	Eye Irrit.	2A	H319

Discovery and Applications

Methyl (R)-(-)-3-hydroxybutyrate, also known as (R)-methyl-3-hydroxybutyrate, is the methyl ester of (R)-3-hydroxybutyric acid, a chiral compound that is naturally occurring in the human body. It plays an essential role in energy metabolism, particularly as part of the ketone body system. In normal physiology, the liver produces (R)-3-hydroxybutyrate during the breakdown of fatty acids, especially during periods of fasting, prolonged exercise, or carbohydrate restriction. The compound serves as an alternative energy source for organs such as the brain, heart, and skeletal muscles, which can utilize ketone bodies when glucose availability is low. Its methyl ester, methyl (R)-3-hydroxybutyrate, is often employed in research studies and clinical applications to better understand the metabolism of ketone bodies and their potential therapeutic effects.

The discovery of methyl (R)-3-hydroxybutyrate is closely linked to studies of polyhydroxyalkanoates, a class of biopolymers produced by microorganisms as energy storage compounds. Early research in the 20th century focused on isolating 3-hydroxybutyric acid and its esters from bacterial polyesters, such as polyhydroxybutyrate. These investigations demonstrated the chiral specificity of naturally occurring hydroxybutyrate and highlighted its potential utility as a building block for biodegradable polymers and fine chemicals. Subsequent work explored synthetic methods for producing the methyl ester from the acid form, often via esterification using methanol in the presence of acid or base catalysts. These methods allowed researchers to obtain high-purity enantiomerically enriched methyl (R)-3-hydroxybutyrate suitable for biochemical and pharmacological studies.

Applications of methyl (R)-3-hydroxybutyrate extend beyond its role as a metabolic substrate. In biochemical research, it is used to study the kinetics and regulation of enzymes involved in ketone body metabolism, such as 3-hydroxybutyrate dehydrogenase. The compound is also useful in investigations of energy metabolism under physiological and pathological conditions, including diabetes, obesity, and ketogenic diets. Because it can be administered exogenously, methyl (R)-3-hydroxybutyrate serves as a tool to elevate plasma levels of ketone bodies in animal models or in vitro systems, allowing researchers to evaluate cellular responses to ketone-based energy sources.

In addition to its research applications, methyl (R)-3-hydroxybutyrate has potential in nutritional and therapeutic contexts. The compound may be explored as a supplement to support energy metabolism in situations where glucose utilization is impaired or insufficient. For example, in endurance sports, exogenous ketone esters, including methyl (R)-3-hydroxybutyrate, have been studied for their ability to provide a readily available energy substrate, potentially enhancing performance and reducing reliance on glycogen stores. Clinical investigations have also examined the use of ketone esters in neurological conditions, as the brain can efficiently utilize ketone bodies as an alternative fuel. These studies suggest that methyl (R)-3-hydroxybutyrate could have a role in supporting cognitive function or in the management of metabolic disorders.

From a chemical perspective, methyl (R)-3-hydroxybutyrate is valued for its stability, water solubility, and chiral purity. Its ester functionality facilitates incorporation into more complex molecules or polymers, while the hydroxyl group allows for derivatization or enzymatic reactions. Industrially, the compound is produced either through chemical synthesis from the acid or through enzymatic processes that leverage microbial polyhydroxybutyrate as a precursor. These methods enable the production of high-quality material for both research and potential therapeutic use.

Overall, methyl (R)-(-)-3-hydroxybutyrate represents a biologically and chemically important compound with diverse applications in metabolism research, nutritional supplementation, and potential therapeutic strategies. Its chiral nature, metabolic significance, and utility as a ketone ester highlight its value in scientific studies and its potential for translational applications in human health.

References

2016. Spirocyclic Orthoesters, Orthothioesters and Orthoaminals in the Synthesis and Structural Modification of Natural Products. Synthesis.
DOI: 10.1055/s-0036-1588339

2020. Biocatalytic Reduction of Keto Esters and Heterocyclic Ketones in Continuous Flow. Synfacts.
DOI: 10.1055/s-0040-1706773

2014. Biocatalytic anti-Prelog reduction of prochiral ketones with whole cells of Acetobacter pasteurianus GIM1.158. Microbial Cell Factories.
DOI: 10.1186/1475-2859-13-84