98% Purity (S)-(-)-Tetrahydro-2-furoic acid CAS 87392-07-2

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.

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.