D(-)-4-Hydroxyphenylglycine (CAS# 22818-40-2), also known as D-4-hydroxyphenylglycine, D-HPG, 4-hydroxy-D-phenylglycine, or (R)-2-amino-2-(4-hydroxyphenyl)acetic acid, is a non-proteinogenic chiral amino acid derivative with the molecular formula C₈H₉NO₃ and a molecular weight of 167.16 g/mol. Its molecular structure features a benzene ring bearing a hydroxyl group at the para position, an α-amino group, and a carboxyl group—conferring optical activity in the D-enantiomer configuration. As a white to off-white crystalline powder with a melting point of approximately 240°C (decomposition), D(-)-4-hydroxyphenylglycine is slightly soluble in water and methanol but readily dissolves in acidic or alkaline solutions to form salts. The compound exhibits a specific optical rotation of -155° to -161° (c=1, 1M HCl).
This chiral amino acid is the definitive side-chain precursor for some of the world’s most widely prescribed antibiotics—most notably amoxicillin and cefadroxil—and serves as a critical building block for vancomycin-class glycopeptide antibiotics. With combined annual sales of amoxicillin and related β-lactam antibiotics exceeding $5 billion globally, D-HPG occupies a strategically vital position in the pharmaceutical supply chain. Based on its chemical characteristics and industrial significance, this article systematically analyzes the key properties, core application areas, global market structure, regional dynamics, regulatory landscape, and future outlook of D(-)-4-hydroxyphenylglycine, providing strategic reference for industry participants.
Core Application Fields and Demand
Market demand for D(-)-4-hydroxyphenylglycine (CAS# 22818-40-2) is overwhelmingly concentrated in the pharmaceutical sector, where it serves as an indispensable chiral building block for semisynthetic β-lactam antibiotics. Over 90% of global consumption is attributable to antibiotic manufacturing, with the remainder used in research, chiral synthesis, and specialty pharmaceutical applications.
In the production of β-lactam antibiotics, D(-)-4-hydroxyphenylglycine functions as the essential side-chain precursor for a broad range of semisynthetic penicillins and cephalosporins. Its most significant application is in the synthesis of amoxicillin (CAS 26787-78-0), one of the most widely prescribed antibiotics globally, used to treat a vast array of bacterial infections including respiratory tract infections, urinary tract infections, skin infections, and Helicobacter pylori-associated peptic ulcer disease. In amoxicillin production, D-HPG is coupled with 6-aminopenicillanic acid (6-APA) to form the complete antibiotic molecule. The compound is also essential for the synthesis of cefadroxil (CAS 66592-87-8), a first-generation cephalosporin antibiotic, as well as cefoperazone, cefradine, ceftriaxone, and other cephalosporin-class drugs. The stereochemistry of the D-enantiomer is critical for drug efficacy, as the L-enantiomer does not possess the same antibiotic activity.
In pharmaceutical research and development, D(-)-4-hydroxyphenylglycine serves as a valuable chiral building block for the synthesis of complex organic molecules, including novel antibiotic agents, antiviral compounds, and artificial sweeteners. It is widely used in biochemical and microbiological assays for developing and studying antibiotic agents. In laboratory settings, it functions as a chiral building block in the synthesis of complex organic molecules.
In the production of D-HPG derivatives, the compound is used to prepare D-4-hydroxyphenylglycine Dane salt (M·K) and OH-EPCP, which are advanced intermediates in the antibiotic manufacturing chain. The methyl ester derivative of D-HPG is increasingly utilized in enzymatic biosynthesis processes for amoxicillin production.
Major Market Participants
The global supply system for D(-)-4-hydroxyphenylglycine (CAS# 22818-40-2) presents an oligopolistic structure, with production heavily concentrated in China. Chinese manufacturers play a dominant role in the global market, accounting for the vast majority of worldwide production capacity.
In the global high-end pharmaceutical segment, key international players include DSM (Netherlands), Kaneka Corporation (Japan), Deretil (Spain), and Daurala Organics (India). These companies supply GMP-compliant, high-purity D-HPG to regulated pharmaceutical markets in Europe, North America, and Japan, with full regulatory documentation and quality assurance.
In the industrial and large-scale production segment, Chinese manufacturers have established an overwhelmingly dominant position. Apeloa Pharmaceutical is the world’s largest manufacturer of D(-)-4-hydroxyphenylglycine, accounting for approximately 40% of the global market share in 2024. Other major Chinese producers include Henan Newland Pharmaceutical, Shanxi Xinbaoyuan Pharmaceutical, Zhejiang Yuntao Biotechnology, The United Laboratories, and Anhui Jingke Biotechnology. These manufacturers leverage China’s integrated pharmaceutical supply chain, cost advantages, and large-scale production capabilities to serve both domestic and export markets.
China not only meets its domestic production requirements but also exports substantial volumes to international markets, solidifying its position as the global production hub for this critical pharmaceutical intermediate.
Regional Market Dynamics
The global D(-)-4-hydroxyphenylglycine market exhibits distinct regional characteristics, with production concentrated in Asia-Pacific (particularly China) and consumption distributed across North America, Europe, and emerging pharmaceutical markets.
The global D-4-hydroxyphenylglycine market was valued at approximately US
239–255millionin2024–2025∗∗andisprojectedtoreach∗∗US 294–350 million by 2031, growing at a compound annual growth rate (CAGR) of 3.5–5.3% during the forecast period. Different research reports provide varying estimates based on methodology, with one projection indicating growth from US
239millionin2025toUS 294 million in 2031 at a CAGR of 3.5%, while another forecasts growth from US
255millionin2025toUS 346 million in 2031 at a CAGR of 5.3%.
The Asia-Pacific region is the dominant force in the global D-HPG market, accounting for the largest share of both production and consumption. China serves as the world’s manufacturing hub, with extensive production capacities and integrated supply chains spanning from raw materials to finished antibiotic APIs. The rapid growth of China’s pharmaceutical industry, combined with increasing domestic demand for antibiotics, continues to drive regional consumption. India has also emerged as an important consumer and producer of D-HPG and its derivatives, with manufacturers such as Daurala Organics serving both domestic and export markets.
North America remains a key market for high-purity, GMP-compliant D-HPG, driven by demand from the pharmaceutical industry and contract manufacturing organizations. The United States market is estimated to increase steadily through 2031. The region relies heavily on imports for this intermediate while maintaining stringent quality and regulatory standards.
Europe is characterized by strict regulatory requirements, including REACH compliance, and a strong focus on quality and sustainability in pharmaceutical manufacturing. European consumption is driven by finished drug manufacturing, but the region relies substantially on imports from Asia-Pacific for the D-HPG intermediate. European manufacturers such as DSM and Deretil serve high-end pharmaceutical applications with GMP-compliant products.
Japan represents a specialized market for high-purity D-HPG, with Kaneka Corporation serving domestic pharmaceutical manufacturing needs.
Regulatory and Safety Considerations
As a pharmaceutical intermediate used in the synthesis of active pharmaceutical ingredients (APIs), D(-)-4-hydroxyphenylglycine (CAS# 22818-40-2) is subject to regulatory oversight in major global economies. Compliance with relevant regulations is essential for market access and trade.
In the United States, D(-)-4-hydroxyphenylglycine is listed in the EPA Substance Registry System under Benzeneacetic acid, α-amino-4-hydroxy-, (αR)-. The compound has a Unique Ingredient Identifier (UNII) of PCM9OIX717. While no specific FDA drug approvals exist for the compound itself, it is regulated as a pharmaceutical intermediate and must meet relevant quality standards for use in API manufacturing. The compound is listed on the TSCA inventory.
In the European Union, D(-)-4-hydroxyphenylglycine has an EINECS number of 245-247-7 and must comply with REACH registration requirements for import and use. Manufacturers and suppliers must provide comprehensive Safety Data Sheets (SDS) and maintain appropriate documentation.
GHS classification and handling: D(-)-4-Hydroxyphenylglycine is classified as an irritant (Xi) with hazard statements H315 (causes skin irritation), H319 (causes serious eye irritation), and H335 (may cause respiratory irritation). The signal word is “Warning”. Precautionary statements include P261 (avoid breathing dust/fume/gas/mist/vapors/spray), P305+P351+P338 (IF IN EYES: Rinse cautiously with water for several minutes; remove contact lenses if present and easy to do; continue rinsing). Personal protective equipment should include dust mask type N95 (US), eyeshields, and gloves.
Transport information: D(-)-4-Hydroxyphenylglycine is not classified as hazardous material for DOT/IATA transport purposes. Proper packaging, labeling, and documentation are nevertheless required for international shipping in compliance with the International Maritime Dangerous Goods Code (IMDG Code) and other transport regulations.
Storage and stability: The compound should be stored long-term in a cool, dry place in tightly closed containers. It has a German WGK (water hazard class) classification of 3, indicating high hazard to water.
Future Outlook
The market outlook for D(-)-4-hydroxyphenylglycine is positive, supported by several key growth drivers across its primary application segments. The global market is expected to maintain steady growth through 2031, with a projected CAGR of 3.5–5.3%.
Key growth drivers include:
- Expanding global antibiotic market: The continued growth of the global antibiotics market, driven by rising bacterial infection rates, increasing resistance to older antibiotics, and expanding access to healthcare in developing countries, sustains demand for D-HPG as a critical intermediate.
- Sustained demand for amoxicillin: Amoxicillin remains one of the most widely prescribed antibiotics globally. Continued growth in amoxicillin API production—particularly in China and India—directly drives demand for D-HPG.
- Growth in cephalosporin antibiotics: Increasing market demand for cephalosporin antibiotics such as cefoperazone, cefadroxil, and cefprozil further boosts demand for D-HPG.
- Preference for green/enzymatic production: The biosynthesis method for amoxicillin API is gradually becoming mainstream due to its environmental advantages, which is expected to further boost demand for D-HPG methyl ester used in this process.
- Increasing market concentration: Leading enterprises in the industry are continuously expanding their scale and improving technology, leading to a gradual increase in market concentration. This consolidation enables economies of scale and more stable supply chains.
- Expansion of pharmaceutical manufacturing in emerging markets: The growth of pharmaceutical manufacturing capacity in China, India, and other emerging economies drives increasing demand for high-quality pharmaceutical intermediates.
Challenges and considerations:
- Raw material price volatility: Fluctuations in the prices of starting materials for D-HPG synthesis may impact production costs.
- Regulatory compliance: Increasingly stringent pharmaceutical and environmental regulations may require ongoing investment in quality systems and documentation.
- Antibiotic stewardship pressures: Global efforts to reduce unnecessary antibiotic use could potentially moderate long-term demand growth.
- Competition from alternative synthetic routes: The market faces potential competition from alternative manufacturing processes and intermediates.
- Supply chain concentration risk: The heavy concentration of production in China creates potential supply chain vulnerabilities that may concern international buyers seeking diversification.
To succeed in this evolving market landscape, suppliers must focus on product quality (particularly for pharmaceutical-grade applications requiring high purity and consistent stereochemical integrity), supply chain reliability, regulatory compliance, and the development of sustainable production methods. Companies that can offer high-purity products, flexible packaging options, and responsive technical support will be well-positioned to capture growing demand.
Shanghai XinChem Co., Ltd. (XinChem)
As a world-leading supplier of organic chemicals and pharmaceutical intermediates, Shanghai XinChem Co., Ltd. (XinChem) is dedicated to meeting the innovative needs of the pharmaceutical, biotechnology, and fine chemical industries. Leveraging extensive experience and advanced manufacturing capabilities, XinChem provides high-quality D(-)-4-Hydroxyphenylglycine (CAS# 22818-40-2) to customers worldwide. As a trusted manufacturer and supplier based in China, XinChem combines competitive pricing, reliable supply, and exceptional service to establish itself as a preferred partner for businesses seeking this essential chiral pharmaceutical intermediate.
1. Technical Advantages
Advanced Synthesis and Purification Processes
XinChem utilizes state-of-the-art manufacturing facilities and rigorous quality control measures to ensure the purity, consistency, and safety of its D(-)-4-hydroxyphenylglycine products. The production process incorporates advanced synthetic technologies, including chemoenzymatic and catalytic hydrogenation routes, enabling the delivery of pharmaceutical-grade products with purity ≥98.0% and ≥99.0% (HPLC/CHN) to meet diverse application requirements. Strict process control ensures consistent optical purity, with specific optical rotation maintained at -155° to -161° (c=1, 1M HCl), and batch-to-batch reproducibility, providing customers with reliable performance in their antibiotic synthesis processes.
Full-Chain Quality Control
The production process strictly adheres to international quality standards, with comprehensive quality control covering raw material sourcing, in-process monitoring, and finished product testing. Each batch is accompanied by a detailed Certificate of Analysis (COA) documenting physical and chemical properties, purity data, optical rotation, and impurity profiles. This commitment to quality ensures that XinChem’s D(-)-4-hydroxyphenylglycine meets the stringent requirements of pharmaceutical API manufacturing and research applications.
2. Product Advantages
High Purity and Consistent Quality
XinChem offers D(-)-4-hydroxyphenylglycine in multiple purity grades: Pharmaceutical Grade with purity ≥99.0% (HPLC) and Technical Grade with purity ≥98.0% (HPLC/CHN). The product’s high purity and consistent stereochemical integrity minimize the risk of unwanted side reactions and impurities in antibiotic synthesis, making it suitable for demanding pharmaceutical applications.
Comprehensive Specifications
Key specifications include:
- Appearance: White to off-white crystalline powder
- Molecular Formula: C₈H₉NO₃
- Molecular Weight: 167.16 g/mol
- Melting Point: ~240°C (decomposition)
- Specific Optical Rotation: -155° to -161° (20°C, 589 nm, c=1, 1M HCl)
- Assay (HClO₄ titration): ≥98.0%
- Purity (HPLC/CHN): ≥98.0% / ≥99.0%
- EINECS: 245-247-7
- MDL: MFCD00004262
Flexible Packaging Solutions
XinChem provides a range of packaging options to accommodate diverse customer needs, from laboratory-scale quantities (1g, 5g, 25g, 100g, 500g, 1kg) to industrial-scale drums (25kg, 200kg) and bulk shipments. Customized packaging solutions are available upon request, ensuring safe handling, storage, and transportation. Recommended storage conditions include storage in a cool, dry place in tightly closed containers, protected from moisture and light.
3. Application Fields
As a versatile chiral pharmaceutical intermediate, D(-)-4-Hydroxyphenylglycine (CAS# 22818-40-2) exhibits wide application value across multiple industries:
Antibiotic Manufacturing:
- Essential side-chain precursor for amoxicillin (CAS 26787-78-0), one of the world’s most prescribed antibiotics
- Key intermediate for cefadroxil (CAS 66592-87-8), a first-generation cephalosporin antibiotic
- Building block for cefoperazone, cefradine, ceftriaxone, and other cephalosporin-class antibiotics
- Critical component in the synthesis of vancomycin-class glycopeptide antibiotics
Pharmaceutical Intermediates:
- Production of D-4-hydroxyphenylglycine Dane salt (M·K)
- Synthesis of OH-EPCP and other advanced antibiotic intermediates
- Precursor for D-HPG methyl ester used in enzymatic biosynthesis processes
Pharmaceutical Research:
- Chiral building block for the synthesis of novel antibiotic agents and antiviral compounds
- Valuable reagent in biochemical and microbiological assays
- Key intermediate in the synthesis of complex organic molecules and artificial sweeteners
4. Service Support
Technical Expertise and Customized Solutions
XinChem’s team of experienced chemists and pharmaceutical engineers provides full technical support throughout the customer journey—from product selection and specification development to application guidance and troubleshooting. Whether customers require optimization of antibiotic synthesis parameters, guidance on handling and storage, or assistance with regulatory documentation, XinChem’s technical experts are ready to help.
Global Logistics and Reliable Supply
With established supply chains serving markets across Europe, North America, Asia-Pacific, and beyond, XinChem ensures timely delivery and consistent product availability. The company’s logistics team manages all aspects of international shipping, including customs clearance and documentation, with the compound classified as non-hazardous material for transport.
Regulatory Support
XinChem provides comprehensive documentation to support regulatory compliance, including Safety Data Sheets (SDS), Certificates of Analysis (COA), and other required certificates. The company stays current with evolving regulatory requirements in major markets, including REACH, FDA, TSCA, and other regional regulations, helping customers navigate the complexities of global pharmaceutical trade.
5. Reasons to Choose XinChem
- Professionalism: Extensive experience and deep expertise in pharmaceutical intermediate synthesis and supply.
- Quality: Rigorous quality control, consistent stereochemical purity, and adherence to international pharmaceutical standards.
- Reliability: Stable supply, competitive pricing, and timely delivery.
- Flexibility: Customized solutions to meet diverse customer needs, including custom synthesis and packaging.
- Service: Responsive technical support and comprehensive documentation.
Contact us today to start your partnership with XinChem!
Website: www.xinchem.com
Email: sales1@xinchem.com
WhatsApp: +86 18049800532
Post time: Aug-26-2026