Kwas szikimowy AHA 20g

Shikimic Acid

Other Names: Shikimate, (3R,4S,5R)-3,4,5-Trihydroxycyclohex-1-ene-1-carboxylic acid, 3,4,5-Trihydroxy-1-cyclohexene-1-carboxylic acid
Chemical Formula: C₇H₁₀O₅
Molar Mass: 174.15 g/mol
CAS Number: 138-59-0
SMILES: C1C(C(C(C=C1C(=O)O)O)O)O
Appearance: White to off-white crystalline powder
Odor: Practically odorless

Shikimic acid is a naturally occurring hydroaromatic carboxylic acid containing three hydroxyl groups and three stereogenic centers. Structurally, it consists of a cyclohexene ring bearing a carboxylic acid group and three adjacent hydroxyl substituents. This highly functionalized and stereochemically defined structure makes shikimic acid a valuable chiral building block in synthetic organic chemistry. In biological systems, shikimic acid is a central intermediate of the shikimate pathway, a metabolic sequence occurring primarily in plants, bacteria, fungi and other microorganisms. The pathway connects carbohydrate metabolism with the biosynthesis of numerous aromatic compounds and proceeds through shikimate toward chorismate, an important metabolic branching intermediate.

Chemical and physical properties

Shikimic acid is a polar crystalline organic compound with a molar mass of approximately 174.15 g/mol. It is generally obtained as a white to off-white crystalline powder. Reported thermal data place its melting point at approximately 185–187 °C, with decomposition possible under sufficiently strong heating.

The molecule contains three hydroxyl groups and one carboxylic acid functionality, giving it extensive hydrogen-bonding capability. These functional groups strongly influence its crystal structure, aqueous behavior and interactions with polar solvents.

Shikimic acid is soluble in water and other strongly polar media, whereas its solubility is substantially lower in many nonpolar organic solvents. In aqueous solution, the carboxylic acid group undergoes acid-base dissociation to form the corresponding shikimate anion.

The three stereogenic centers of naturally occurring shikimic acid give the compound a well-defined three-dimensional configuration. This stereochemical complexity is particularly important in synthetic chemistry because the existing stereocenters can be exploited in the preparation of structurally complex chiral molecules.

Shikimic acid is an intermediate of the seven-step shikimate pathway. In microorganisms, phosphoenolpyruvate and erythrose-4-phosphate are ultimately converted through several enzymatic reactions into 3-dehydroshikimate, which is reduced by shikimate dehydrogenase to shikimic acid. Shikimate is subsequently phosphorylated and transformed through further enzymatic steps toward chorismate.

Applications

Shikimic acid is an important chiral starting material in synthetic organic and medicinal chemistry. Its combination of a carboxylic acid group, an alkene and three stereochemically defined hydroxyl groups provides multiple sites for selective chemical modification. Numerous synthetic methodologies have therefore been developed to transform shikimic acid into structurally diverse intermediates and biologically active molecules.

One of its best-known applications is as a starting material in the multistep chemical synthesis of oseltamivir, an antiviral neuraminidase inhibitor. The pre-existing stereochemistry of shikimic acid is particularly valuable in this synthesis because it provides a suitable chiral framework from which the stereochemically complex target molecule can be constructed.

Shikimic acid is also used as a platform compound for the synthesis of other functionalized cyclohexene derivatives, aromatic compounds and heterocyclic structures. Chemical modification of its hydroxyl, carboxyl and alkene functionalities allows access to numerous derivatives for investigations in organic synthesis and medicinal chemistry.

In biochemical research, shikimic acid is used to investigate the enzymes and regulation of the shikimate pathway. Because this metabolic pathway is present in many microorganisms and plants but differs substantially from mammalian metabolic pathways, its individual enzymes are extensively studied in enzymology, structural biology and inhibitor-development research.

Shikimic acid is also an important compound in metabolic engineering. Recombinant microorganisms, particularly engineered strains of Escherichia coli and Corynebacterium glutamicum, have been developed to accumulate shikimic acid by redirecting carbon flux through the shikimate pathway. Such research involves modification of pathway enzymes, precursor availability, cofactor balance and competing metabolic reactions.

In analytical chemistry, shikimic acid can serve as a reference compound for chromatographic and spectroscopic investigations of plant extracts, microbial fermentation products and reaction mixtures. High-performance liquid chromatography and related analytical methods are commonly employed for its identification and quantitative determination.

Scientific references

Ghosh, S.; Chisti, Y.; Banerjee, U. C. Production of shikimic acid. Biotechnology Advances, 2012, 30(6), 1425–1431. DOI: 10.1016/j.biotechadv.2012.03.001.

Sheng, Q.; Yi, L.; Zhong, B.; Wu, X.; Liu, L.; Zhang, B. Shikimic acid biosynthesis in microorganisms: Current status and future direction. Biotechnology Advances, 2023, 62, 108073. DOI: 10.1016/j.biotechadv.2022.108073.

Herrmann, K. M.; Weaver, L. M. The Shikimate Pathway. Annual Review of Plant Physiology and Plant Molecular Biology, 1999, 50, 473–503. DOI: 10.1146/annurev.arplant.50.1.473.

Draths, K. M.; Knop, D. R.; Frost, J. W. Shikimic acid and quinic acid: replacing isolation from plant sources with recombinant microbial biocatalysis. Journal of the American Chemical Society, 1999, 121(7), 1603–1604. DOI: 10.1021/ja9831753.

Krämer, M.; Bongaerts, J.; Bovenberg, R.; Kremer, S.; Müller, U.; Orf, S.; Wubbolts, M.; Raeven, L. Metabolic engineering for microbial production of shikimic acid. Metabolic Engineering, 2003, 5(4), 277–283. DOI: 10.1016/j.ymben.2003.09.001.

Safety
Signal Word: Danger

Hazard Statements:
H319: Causes serious eye irritation.

Precautionary Statements:
P101: If medical advice is needed, have product container or label at hand.
P102: Keep out of reach of children.
P280: Wear eye protection.
P305+P351+P338: IF IN EYES: Rinse cautiously with water for several minutes. Remove contact lenses, if present and easy to do. Continue rinsing.
P310: Immediately call a POISON CENTER/doctor.

First Aid Measures
General: Ensure your own safety. If symptoms occur or in case of doubt, seek medical advice and provide information from the safety data sheet. If unconscious, place the victim in the recovery position with the head slightly tilted and airways open. Never induce vomiting. If the victim vomits, prevent aspiration. In life-threatening situations, perform resuscitation and ensure medical assistance. Perform artificial respiration in case of apnea. For cardiac arrest, perform chest compressions immediately.

Inhalation: Move to fresh air immediately.

Skin Contact: Remove contaminated clothing. Rinse skin with plenty of lukewarm water. If the skin is uninjured, soap or shampoo may be used. Seek medical advice if irritation persists.

Eye Contact: Do not rub eyes. Rinse immediately with a stream of water. Force eyelids open if necessary. Remove contact lenses if present. Do not neutralize. Rinse for 10–30 minutes from the inner to the outer corner of the eye. Call emergency services or seek medical help immediately. Every case of contamination should be examined by a medical professional.

Ingestion: Rinse mouth with clean water. Seek medical advice in case of discomfort.