(S)-(−)-Tetrahydro-2-furoic acid CAS 87392-07-2 is a chiral, non-proteinogenic carboxylic acid featuring a saturated furan ring (tetrahydrofuran, THF) with a carboxylic acid group at the 2-position. It is the single (S)-enantiomer of 2-tetrahydrofuroic acid, a valuable chiral building block in organic synthesis. This compound is a high-value, enantiomerically pure chiral building block that provides a ready-to-use, metabolically stable, and conformationally constrained tetrahydrofuran (THF) carboxylic acid scaffold in the (S)-configuration. Its primary value lies in enabling efficient, stereocontrolled synthesis of complex molecules for life sciences.
Nome :
(S)-(-)-Tetrahydro-2-furoic acidNº CAS. :
87392-07-2MF :
C₅H₈O₃MW :
116.12Pureza :
98%Aparência :
Typically a white to off-white crystalline powder or low-melting solid.Condição de armazenamento :
Store in a tightly sealed container in a cool, dry place. For long-term storage ( > 6 months), a refrigerator (2-8°C) is recommended.Chemical Properties
IUPAC Name: (S)-Tetrahydrofuran-2-carboxylic acid
Other Common Names: (S)-2-Carboxytetrahydrofuran; L-Tetrahydro-2-furoic acid (historical, non-standard)
Chemical Formula: C₅H₈O₃
Molecular Weight: 116.12 g/mol
Specific Rotation: [α]²⁰_D ≈ -15° to -20° (c=1 in H₂O or other solvent, exact value varies)
Structure: A five-membered tetrahydrofuran ring with an (S)-configured stereocenter at the carbon alpha to the carboxylic acid group (C2).
Appearance: Typically a white to off-white crystalline powder or low-melting solid.
Melting Point: ~ 35-40 °C (can vary based on purity and crystalline form)
Boiling Point: Decomposes upon distillation; typically used below 150°C.
Solubility: Soluble in water, lower alcohols (methanol, ethanol), and polar organic solvents (THF, ethyl acetate). Sparingly soluble in non-polar solvents like hexane.
Acidity: pKa ~3.5-4.0, typical for an aliphatic carboxylic acid.
Stability: Stable under normal storage conditions. The ester and amide derivatives are often more stable and commonly used in synthesis.
Reactivity: Exhibits standard carboxylic acid reactivity:
Esterification/Amidation: Can form esters and amides.
Reduction: Can be reduced to the corresponding alcohol, (S)-tetrahydrofurfuryl alcohol.
Decarboxylation: Under specific conditions, can undergo decarboxylation.
Chiral Pool Synthon: The chiral THF ring is retained and used to transfer chirality to more complex molecules.
Biological Activities
Natural Occurrence & Metabolism: Not a major natural metabolite but may occur as a minor component or degradation product. It is structurally related to furanoid fatty acid metabolites and may serve as a precursor or analog in certain biochemical pathways.
Biological Activity: No significant, well-characterized intrinsic pharmacological activity as a standalone compound. Its primary importance is as a metabolically stable isostere or conformationally constrained scaffold in medicinal chemistry.
Isostere: The THF ring can serve as a bioisostere for a cyclopentane or a saturated ribose moiety.
Toxicity: Expected to have low acute toxicity but may be irritating to eyes, skin, and mucous membranes. No specific severe hazards are widely reported, but it should be handled as a standard laboratory chemical.
Biosynthesis
Natural Biosynthesis: Not a primary natural product; no major dedicated biosynthetic pathway is known.
Industrial/Chemical Synthesis: Produced via asymmetric synthesis or chiral resolution.
1.Asymmetric Hydrogenation: A key industrial route involves the asymmetric hydrogenation of commercially available furan-2-carboxylic acid or its derivatives using chiral ruthenium or rhodium catalysts, directly yielding the enantiomerically enriched product.
2.Chiral Pool Starting Materials: Synthesis from other chiral natural products (e.g., sugars like ribose) is possible but less common for large-scale production.
3.Enzymatic Resolution: Kinetic resolution of racemic tetrahydro-2-furoic acid (or its esters) using lipases or esterases can yield the desired (S)-enantiomer.
Applications
Key Advantages & Benefits
1. Ready-to-Use Chiral Pool Synthon with High Stereochemical Integrity
Benefit: Provides immediate access to a defined (S)-configured stereocenter attached to a versatile carboxylic acid handle, eliminating the need for costly and inefficient chiral resolutions or asymmetric transformations later in a synthesis.
Application Scenario: In the late-stage diversification of a drug candidate library targeting a protease, medicinal chemists can directly couple this acid to various amine cores using standard amide coupling reagents. This rapidly generates a series of analogs with a conserved, chiral, rigid side chain, allowing for precise SAR studies around the lipophilic binding pocket without racemization risks.
2. Ideal Bioisostere and Conformationally Constrained Scaffold
Benefit: The saturated THF ring acts as a stable, non-planar bioisostere for other cyclic systems (like cyclopentane) or as a constrained analog of flexible butyric acid chains. It imposes specific three-dimensional geometry, improving target binding affinity and metabolic stability.
Application Scenario: When developing a novel GABAergic modulator, replacing a flexible alkyl chain in a lead compound with the (S)-THF scaffold locks the carboxylate group in a specific orientation. This dramatically increases potency and reduces off-target effects by preventing unproductive conformations, while the ether oxygen can provide subtle hydrogen-bonding interactions.
3. Dual Functional Group for Facile Diversification
Benefit: The carboxylic acid group is a universal linchpin for synthetic elaboration (amidation, esterification, reduction), while the THF ether offers additional sites for functionalization (e.g., C-H activation at adjacent positions) or influences physicochemical properties.
Application Scenario: In synthesizing a chiral ligand for asymmetric catalysis, the acid is first converted to an amide with a chiral amine. The THF ring's oxygen can then be used to tether additional coordinating groups (like phosphines), creating a privileged P,O-ligand class used in enantioselective hydrogenation reactions for pharmaceutical manufacturing.
4. Favorable Physicochemical Profile
Benefit: Contributes to an improved balance of lipophilicity and solubility. The THF ring increases lipophilicity (LogP) versus a linear chain, aiding membrane permeability, while the ether oxygen and acid group provide points for solvation and salt formation.
Application Scenario: In optimizing the oral bioavailability of a peptide mimetic, incorporating (S)-tetrahydro-2-furoic acid as a proline replacement at a critical position enhances cell permeability by masking polar character, without resorting to fully non-polar groups that would kill aqueous solubility necessary for formulation.
(S)-(−)-Tetrahydro-2-furoic Acid (CAS 87392-07-2) is a strategic, high-purity chiral building block that offers a unique combination of stereochemical definition, structural rigidity, and synthetic versatility. It is not a commodity chemical but a precision tool for drug discoverers and synthetic chemists. Its greatest strength is the ability to impart optimal three-dimensional shape and improved drug-like properties into a target molecule from the earliest stages of design. For projects requiring a metabolically stable, non-basic, and spatially defined carboxylic acid component, it provides a superior and often irreplaceable solution compared to more common chiral acids like proline or linear chains, accelerating the path to optimized leads and final active ingredients.
FAQs
Q1: What is the key value proposition of the (S)-enantiomer specifically?
A: The (S)-configuration is a specific, defined spatial arrangement required for the biological activity or stereochemical outcome in the final target molecule. Using the single enantiomer ensures:
Predictable pharmacology in drug candidates.
High enantioselectivity when used to make chiral catalysts or ligands.
Regulatory compliance for pharmaceutical development, where racemates are often undesirable.
Q2: What is the critical specification to confirm when ordering for chiral synthesis?
A: Enantiomeric Excess (e.e.) is paramount. For most synthetic applications, a minimum of >98% e.e. is required, with >99% e.e. being the standard for advanced intermediates. Always request a certificate of analysis (CoA) with the specific optical rotation and e.e. value (typically determined by chiral HPLC or GC).
Q3: How should it be stored to maintain stability and chiral purity?
A: Store in a tightly sealed container in a cool, dry place. For long-term storage ( > 6 months), a refrigerator (2-8°C) is recommended. While it is not particularly prone to racemization under standard conditions, protecting it from heat and moisture preserves both chemical and chiral purity.
Q4: What are the most common next-step transformations performed with this acid?
A: It is most frequently converted into more robust and versatile derivatives:
Activated Esters: Conversion to the acid chloride, or formation of pentafluorophenyl (PFP) or N-hydroxysuccinimide (NHS) esters for efficient amide coupling.
Direct Amide Coupling: Using peptide coupling reagents (e.g., HATU, EDC) with amines to form chiral amides.
Esterification: To form methyl or ethyl esters for use as intermediates or for chiral GC analysis.
Q5: Can it be used as a direct substitute for proline or other cyclic amino acids?
A: Not directly, but it is a valuable bioisostere. It lacks the amine group of proline but offers a metabolically stable, conformationally constrained carboxylic acid. It is used in drug design to replace other cyclic structures to modulate properties like polarity, metabolic stability, and 3D shape without basic nitrogen's pharmacology.
Q6: What are typical impurity profiles, and how do they affect synthesis?
A: Key impurities to monitor include:
The (R)-enantiomer: The primary concern. Even 1-2% can significantly impact the e.e. of downstream products.
Furan-2-carboxylic acid: A potential starting material.
Over-reduction products or dimers.
Impurities can lower yields, complicate purifications, and critically, compromise the stereochemical integrity of the final product.
Q7: What is the primary competitive advantage over the racemic mixture?
A: Using the enantiopure (S)-form eliminates the need for a costly and wasteful resolution step later in the synthesis. It provides immediate stereochemical control, streamlining the synthetic route, improving overall yield, and reducing waste—key principles of efficient and green chiral synthesis. It is a cost-saver in the total synthesis of complex chiral molecules.
Cloridrato de Procaína CAS 51-05-8 é o sal cloridrato de procaína solúvel em água. É a formulação específica usada na medicina clínica, comercializada sob a famosa marca Procaína.NovocaínaEmbora seu uso na prática clínica tenha diminuído, continua sendo um medicamento historicamente fundamental e ainda é empregado em contextos médicos e terapêuticos específicos.
Detalhes
L(+)-Choline bitartrate CAS 87-67-2 is an organic salt compound formed from one molecule of choline (a quaternary ammonium cation and essential nutrient) and one molecule of L(+)-tartaric acid (a natural dicarboxylic acid). It is a specific, enantiomerically pure form of choline salt where the counterion is derived from natural tartaric acid.It is a high-purity, stable, and highly bioavailable source of essential choline, combining the vital nutrient with a natural, food-grade organic acid. It offers a superior balance of safety, solubility, and cost-effectiveness for dietary supplementation and food fortification.
Detalhes
L-Carnitine CAS 541-15-1 is a naturally occurring, quaternary ammonium compound biosynthesized from the amino acids lysine and methionine. It is a chiral molecule, with the L-enantiomer being the biologically active form. Structurally, it functions as a carrier molecule for long-chain fatty acids. L-Carnitine is the essential biological shuttle required for transporting long-chain fatty acids into the mitochondria for energy production. It is a conditionally essential nutrient that optimizes cellular energy metabolism, making it fundamental for muscular, cardiovascular, and metabolic health.
Detalhes
L-Carnitine-L-tartrate CAS 36687-82-8 is a well-defined, crystalline salt formed through the ionic bonding of one molecule of L-carnitine (the biologically active enantiomer) and one molecule of L-tartaric acid (the naturally occurring enantiomer). It is specifically engineered as a superior solid form of carnitine for dietary supplements and functional foods. L-Carnitine-L-tartrate is a non-hygroscopic, highly stable salt form of L-carnitine, specifically engineered for superior manufacturing and performance. It delivers the essential metabolic benefits of L-carnitine with added advantages for physical recovery, excelling in solid-dose and powdered supplement formulations where stability and clinical validation are paramount.
Detalhes
Trimethylamine hydrochloride (TMA·HCl) CAS 593-81-7 is the hydrochloride salt of trimethylamine (TMA), a simple tertiary alkylamine. It is a solid, crystalline form of the normally gaseous and foul-smelling trimethylamine, which makes it much more convenient to handle, store, and weigh precisely.Trimethylamine Hydrochloride is the safe, stable, and precisely weighable solid equivalent of gaseous trimethylamine (TMA). It transforms a hazardous, malodorous gas into a controllable reagent, eliminating the major handling and safety challenges while enabling exact stoichiometry in critical synthetic steps.
Detalhes
(S)-4-Chloro-3-hydroxybutyronitrile CAS 127913-44-4 is a chiral, bifunctional organic molecule serving as a versatile building block in asymmetric synthesis. It features a nitrile group, a secondary alcohol with defined (S)-stereochemistry, and a terminal chloro substituent, allowing for multiple divergent chemical transformations from a single, enantiomerically pure scaffold.(S)-4-Chloro-3-hydroxybutyronitrile is a privileged, enantiomerically pure chiral building block that provides a compact, multifunctional scaffold with three differentiable reaction sites. Its core value lies in enabling the efficient, stereocontrolled synthesis of complex chiral molecules, particularly pharmacologically active intermediates, with high atom economy and strategic flexibility.
Detalhes
Ethyl (S)-4-chloro-3-hydroxybutyrate CAS 86728-85-0 is a chiral, bifunctional ester and a highly valuable building block in asymmetric synthesis. It features a terminal chloro group, a secondary alcohol with defined (S)-stereochemistry, and an ethyl ester, providing three distinct reactive handles for chemical transformation from a single enantiomerically pure scaffold. This compound is a chirally pure, trifunctional building block that integrates a reactive ethyl ester, a stereodefined secondary alcohol, and a terminal chloride into a compact C4 skeleton. It is the preferred industrial precursor for synthesizing the chiral side chain of blockbuster statin drugs due to its optimal balance of reactivity, stability, and efficient biocatalytic production.
Detalhes
Ethyl (R)-4-cyano-3-hydroxybutyrate CAS 141942-85-0 is a chiral, bifunctional building block of significant importance in asymmetric synthesis. It contains a stereogenic center with (R)-configuration, an ethyl ester group, and a terminal nitrile group, making it a versatile precursor for constructing complex chiral molecules, particularly in pharmaceutical applications. This compound is a stereodefined, multifunctional chiral building block where the (R)-configured alcohol and versatile cyano group provide unique synthetic leverage. It serves as a privileged precursor for high-value pharmaceutical intermediates, particularly statin side chains, by offering superior and orthogonal reactivity compared to its chloro analog.
Detalhes
CONTATE-NOS
1st Floor, No. 477, Huancheng West Road, Nanqiao Town, Fengxian District, Shanghai,China
sales@qxscientific.com
+86 -13701740203
IPv6 SUPORTADO POR REDE
|
Mapa do site
|
XML |
Blogue |
política de Privacidade
Deixe um recado
Scan to Wechat/Whatsapp :
Português
English
Español
Português
