4- (Hydroxymethyl) phenylacetic acid (CAS: 73401-74-8): A multifunctional PAM linker in peptide synthesis and drug development
In the fields of medicinal chemistry and peptide science, the selection of appropriate linkers or intermediates often determines the success or failure and efficiency of synthesis. 4- (Hydroxymethyl) phenylacetic acid (CAS: 73401-74-8) is a star molecule that combines dual functional reactivity and wide application value. As a classic PAM (phenylacetamidomethyl) linker, it plays an irreplaceable role in solid-phase peptide synthesis (SPPS), small molecule drug preparation, and chemical biology research.
1. Product Overview: Key Parameters and Structural Features
English name: 4- (Hydroxymethyl) phenylacetic acid
Molecular formula: C ₉ H ₁ O ∝
Molecular weight: 166.17
CAS number: 73401-74-8
Appearance: White to off white crystalline powder
Melting point: 127-134 ° C
Purity specification: ≥ 98% (HPLC) to ≥ 99% (GC)
Solubility: up to 100 mg/mL (~601 mM) in DMSO
Structural formula:
The two key functional groups on the molecular structure – carboxyl (- COOH) and hydroxymethyl (- CH ₂ OH) – enable selective coupling with solid-phase carriers (resins) and peptide chains or drug fragments to be synthesized, achieving precise and controllable chemical connections.
2. Core application one: PAM linker in solid-phase peptide synthesis (SPPS)
In the solid-phase peptide synthesis of Boc strategy, 4- (hydroxymethyl) phenylacetic acid is known as the PAM linker. It is anchored to the resin through carboxyl groups, and then forms stable ester bonds with the carboxyl group of the first amino acid using hydroxymethyl groups. This design has significant advantages:
Enhanced tolerance to acid unstable peptide chains and reduced shedding during synthesis;
Suitable for synthesizing long-chain peptides or difficult sequences with strong hydrophobicity;
Ultimately, the target peptide can be cleanly cleaved under anhydrous HF or strong acid conditions with minimal side reactions.
Therefore, this compound is widely used in the development of customized peptides, peptide drug analogues, and peptide drug conjugates (PDCs).
3. Core application 2: Construction of drug intermediates and active molecules
In addition to the peptide field, 4- (hydroxymethyl) phenylacetic acid is also a key intermediate for various small molecule drugs. The synthesis process has been scaled up to the kilogram level, and literature reports indicate that using 4-bromomethylphenylacetic acid as the raw material, a total yield of 71.9% and HPLC purity of 97.8% can be achieved through hydrolysis. This compound is used for the synthesis of:
Non steroidal anti-inflammatory drugs (NSAIDs) and novel analgesic molecules;
Tyrosine kinase inhibitors and other anti-tumor drugs;
A cosmetic additive with antioxidant activity.
In addition, due to its unique dual functional group structure, it can also be used as a polymer monomer for the preparation of special polyesters or polyamides, improving the mechanical properties and thermal stability of the materials.
4. Unique value in biochemical research: selective inhibition of 6-mercaptopurine oxidation
As a naturally occurring aromatic acid in gut microbiota metabolites, 4- (hydroxymethyl) phenylacetic acid has shown interesting selective inhibitory effects in enzymatic studies. Research has shown that it can selectively inhibit the oxidative metabolism of 6-mercaptopurine (6-MP) without affecting the conventional activity of xanthine oxidase. This characteristic is:
Study the metabolic pathways of purine drugs;
Exploring the drug microbe interaction mechanism in inflammatory bowel disease;
Developing a combination therapy strategy to improve the efficacy of 6-MP
Provided reliable molecular tools.
5. Safety and Storage Guidelines
Storage conditions: It is recommended to store in a dry, sealed, and dark place at 0-8 ° C for good long-term stability.
Precautions for operation: Avoid inhaling dust, wear goggles, gloves, and laboratory protective clothing during operation. Avoid contact with strong oxidants.
Waste disposal: Dispose of organic halide or aromatic acid waste in compliance with local regulations.
6. Summary
4- (Hydroxymethyl) phenylacetic acid (CAS: 73401-74-8) is a high-purity chemical with multifunctional linking ability and pharmaceutical intermediate value. Whether developing next-generation peptide drugs or exploring highly selective enzyme inhibitors, it is a reliable choice worth including in the research toolbox. With the continuous rise of peptide therapy and targeted drug conjugates, this classic PAM linker is unleashing new application potential.
