The Orthogonally Protected Chiral Pyroglutamate Building Block for Peptide Synthesis, Kinase Inhibitor Development, and Asymmetric Drug Discovery: BOC-D-Pyroglutamic Acid Ethyl Ester (CAS# 144978-35-8)

BOC-D-Pyroglutamic acid ethyl ester (CAS# 144978-35-8), also known as Boc-D-Pyr-Oet, ethyl N-(tert-butoxycarbonyl)-D-pyroglutamate, (R)-1-tert-butyl 2-ethyl 5-oxopyrrolidine-1,2-dicarboxylate, or N-Boc-D-pyroglutamic acid ethyl ester, is an orthogonally protected chiral pyroglutamate derivative with the molecular formula C₁₂H₁₉NO₅ and a molecular weight of 257.28–257.29 g/mol. Its molecular structure features a (2R)-configured pyrrolidinone ring bearing a tert-butoxycarbonyl (Boc) protecting group on the lactam nitrogen and an ethyl ester at the C2 position, creating a doubly protected chiral building block with defined stereochemistry.

As a white to off-white crystalline powder with a melting point of 54.0–58.0°C, a specific optical rotation of +44.0° to +47.0° (c=1, MeOH), and a density of 1.182 g/cm³, the compound is soluble in organic solvents and should be stored in a dark, sealed container at room temperature (2–8°C recommended for long-term storage). It is typically supplied at ≥95% to ≥98% purity (GC/HPLC), with enantiomeric excess ≥99% ee available for demanding applications. The compound is classified with the signal word “Warning” (H315, H319, H335) under GHS and requires standard laboratory safety precautions during handling.

BOC-D-Pyroglutamic acid ethyl ester is a strategically important chiral building block that serves as the definitive orthogonally protected D-pyroglutamate intermediate for solid-phase peptide synthesis (SPPS), the synthesis of pharmacologically active peptides, and the development of kinase inhibitors including PF-06651600 (ritlecitinib). Its unique combination of a (2R)-configured stereocenter, orthogonal Boc and ethyl ester protection, and the pyroglutamate lactam scaffold positions it as an indispensable tool in modern medicinal chemistry and pharmaceutical development. Based on its chemical characteristics and industrial significance, this article systematically analyzes the key properties, core application areas, global market structure, regulatory landscape, and future outlook of this strategically important chiral building block.

Core Application Fields and Demand

Market demand for BOC-D-Pyroglutamic acid ethyl ester (CAS# 144978-35-8) is concentrated in four primary sectors: peptide synthesis and peptidomimetics (approximately 40–45% of global consumption), pharmaceutical development and drug discovery (approximately 30–35%), biochemical assay reagents and research applications (approximately 15–20%), and asymmetric synthesis and chiral building blocks (approximately 10–15%). Its orthogonally protected chiral scaffold and the unique properties of the pyroglutamate ring serve as the core drivers of sustained demand growth.

In peptide synthesis and peptidomimetics, BOC-D-Pyroglutamic acid ethyl ester is a crucial building block for the construction of peptides containing D-pyroglutamic acid residues. The compound is extensively utilized in solid-phase peptide synthesis (SPPS) with orthogonal Boc/Fmoc strategies, enabling the precise formation of peptide bonds through coupling reactions with other amino acid derivatives. The Boc group at the lactam nitrogen is removed cleanly with TFA or HCl in dioxane, making it orthogonal to Fmoc, Cbz, and Alloc protecting groups—a critical feature for the stepwise assembly of complex peptide therapeutics. The ethyl ester at the C2 position serves as a temporary carboxylate mask that can be selectively hydrolyzed, enabling sequential deprotection strategies. It is also used as a substrate for the synthesis of various peptides and peptidomimetics, including anticancer peptides and antimicrobial peptides. The pyroglutamate ring is a privileged structural motif in peptide chemistry, contributing to conformational rigidity and metabolic stability in the resulting peptides.

In pharmaceutical development and drug discovery, BOC-D-Pyroglutamic acid ethyl ester is a key chiral intermediate for the synthesis of biologically active molecules, including protease inhibitors and other therapeutic agents. The compound has been specifically cited in the synthesis of PF-06651600 (ritlecitinib)—a JAK3 inhibitor being developed for autoimmune diseases including alopecia areata and rheumatoid arthritis—demonstrating its importance in the development of next-generation kinase inhibitors. The (2R) configuration of the compound is not a trivial structural detail—it defines the absolute stereochemistry of every downstream chiral center generated from this building block, making it essential for the production of single-enantiomer drugs. The compound is also used as a precursor for the synthesis of various pharmacologically active peptides and as a biochemical assay reagent for studying enzymatic activities and protein interactions.

In biochemical assay reagents and research applications, BOC-D-Pyroglutamic acid ethyl ester serves as a valuable biochemical assay reagent for studying enzymatic activities and protein interactions. Its defined stereochemistry and orthogonal protection make it a reliable tool for researchers investigating enzyme-substrate interactions, protein-ligand binding, and metabolic pathways. The compound is also used in the development of biochemical assays requiring chiral discrimination and enantioselective analysis.

In asymmetric synthesis and chiral building block applications, BOC-D-Pyroglutamic acid ethyl ester provides a defined stereochemical platform for the construction of complex chiral molecules. The (2R)-configured stereocenter ensures downstream chirality with ≥99% ee, preventing diastereomer contamination in multi-step synthesis. The compound is classified as a chiral pyrrolidinone-based amino acid derivative primarily utilized as a protected chiral building block in stereoselective organic synthesis.

Major Market Participants

The global supply system for BOC-D-Pyroglutamic acid ethyl ester (CAS# 144978-35-8) features a pattern of “specialized chiral building block manufacturers, multinational research chemical distributors, and Chinese producers serving distinct market segments.” As a specialized chiral intermediate rather than a bulk commodity, the market is characterized by a moderate number of suppliers catering to pharmaceutical R&D, peptide synthesis, and academic research. According to the global market report on 1-Boc-D-Pyroglutamic Acid Ethyl Ester Reagent, comprehensive data is available on manufacturers, regions, types, and applications with forecasts extending through 2028.

In the global research and high-purity segment, key international suppliers include Tokyo Chemical Industry (TCI), offering the compound at >95.0% purity (GC) under product code E0940, with specifications including a melting point of 54.0–58.0°C and specific rotation of +44.0 to +47.0° (c=1, MeOH). MedChemExpress offers the compound as Boc-D-Pyr-Oet (HY-W003605) with a batch-specific purity of 99.97% (LCMS) and water content of 0.10%, suitable for biochemical assay applications. ChemContract Research supplies the compound at ≥95% purity from its Huntington Beach, California facility under cGMP compliance, with custom grades and full batch documentation including Certificates of Analysis (CoA) and Safety Data Sheets. AK Scientific (AKSci) offers the compound at 97% purity under product code 56216, with pricing from $19 for 1 g to $79 for 25 g. Nordmann (Germany) offers the compound as N-Boc-D-Pyroglutamic acid Ethyl Ester for pharmaceutical compound synthesis, frequently serving as a protecting group for amines. These suppliers serve the pharmaceutical, biotechnology, and academic research communities with products that meet rigorous quality specifications.

In the industrial and large-scale production segment, Chinese manufacturers have emerged as significant players in the global supply chain. XinChem is a reliable manufacturer and supplier of high-purity BOC-D-Pyroglutamic acid ethyl ester from China, offering the compound with stringent quality standards for use in peptide synthesis, pharmaceutical development, and asymmetric synthesis applications. XinChem provides the compound with comprehensive quality documentation, batch-specific Certificates of Analysis (COA), customizable packaging, and globally compliant REACH, ISO 9001, and GMP-aligned manufacturing. Chinese suppliers offer the compound at various purity grades (typically 97–99%) and packaging options—from grams to multi-kilogram quantities—serving both domestic and export markets. Production scale capabilities include up to 500 kg quantities from industrial suppliers, with 25 kg packaging options available. The compound is available at prices ranging from approximately RMB 14–20 per gram for laboratory quantities to competitive bulk pricing for industrial volumes.

Regional Market Dynamics

The global BOC-D-Pyroglutamic acid ethyl ester market exhibits distinct regional characteristics, with production concentrated in Asia-Pacific (particularly China) and consumption distributed across North America, Europe, and the Asia-Pacific region, aligned with the pharmaceutical, peptide synthesis, and biotechnology industries in these regions. The global market report on Butoxycarbonyl-D-pyroglutamic acid ethyl ester (CAS 144978-35-8) covers comprehensive data on markets globally and regionally (Europe, Asia, North America, etc.), including producers, suppliers, prices, and consumers.

The Asia-Pacific region is a significant production and consumption hub for BOC-D-Pyroglutamic acid ethyl ester, with China hosting numerous manufacturers and suppliers including XinChem. The region’s competitive advantages include lower production costs, established chemical infrastructure, and proximity to rapidly growing pharmaceutical and peptide synthesis industries. Chinese suppliers offer the compound at various purity grades (typically 97–99%) and packaging options, serving both domestic and export markets. The growing pharmaceutical R&D, peptide therapeutics, and API manufacturing sectors in China, Japan, South Korea, and India continue to drive regional consumption growth. TCI Chemicals maintains inventory in Japan and China, with the ability to ship from regional warehouses.

North America remains a key market for high-purity and research-grade BOC-D-Pyroglutamic acid ethyl ester, driven by demand from the pharmaceutical industry, biotechnology companies, and academic research institutions. The United States hosts numerous research organizations, pharmaceutical companies, and contract research organizations that require high-quality chiral building blocks for drug discovery and development. ChemContract Research, MedChemExpress, and AK Scientific serve the North American market with extensive distribution networks. The region’s well-established regulatory framework and emphasis on product quality support demand for high-grade research chemicals and pharmaceutical intermediates.

Europe is characterized by stringent regulatory requirements, including REACH registration, and a strong focus on quality and sustainability in pharmaceutical and chemical research. European pharmaceutical companies, peptide synthesis laboratories, and research institutions demand high-purity chiral building blocks with comprehensive documentation. Nordmann (Germany) and other distributors serve the European market with in-stock availability.

Japan represents a specialized market where BOC-D-Pyroglutamic acid ethyl ester is supplied by Tokyo Chemical Industry (TCI) and other distributors for pharmaceutical research, peptide synthesis, and fine chemical applications.

Regulatory and Safety Considerations

As a research chemical, pharmaceutical intermediate, and chiral building block, BOC-D-Pyroglutamic acid ethyl ester (CAS# 144978-35-8) is subject to regulatory oversight in major global economies. Compliance with relevant regulations is essential for market access and trade.

GHS classification and handling: BOC-D-Pyroglutamic acid ethyl ester is classified with the signal word “Warning”. Hazard statements include H315 (Causes skin irritation), H319 (Causes serious eye irritation), and H335 (May cause respiratory irritation). Precautionary statements include P261 (Avoid breathing dust/fume/gas/mist/vapours/spray), P264 (Wash skin thoroughly after handling), P271 (Use only outdoors or in a well-ventilated area), P280 (Wear protective gloves/protective clothing/eye protection/face protection), P302+P352 (IF ON SKIN: Wash with plenty of soap and water), P304+P340 (IF INHALED: Remove person to fresh air and keep comfortable for breathing), P305+P351+P338 (IF IN EYES: Rinse cautiously with water for several minutes; remove contact lenses if present and easy to do; continue rinsing), and P405 (Store locked up). The compound should be stored in a dark place, sealed in dry conditions at room temperature (2–8°C recommended for long-term storage). Personal protective equipment including lab gloves, safety glasses, and a lab coat should be worn during handling, and operations should be conducted in a well-ventilated environment.

Storage and stability: BOC-D-Pyroglutamic acid ethyl ester should be stored in a cool, dark place (recommended <15°C) in a tightly sealed container protected from moisture. For long-term storage, conditions of 2–8°C are recommended. The compound has a shelf life of two years when properly stored.

Regulatory compliance: In the European Union, the compound must comply with REACH registration requirements for import and use. Manufacturers and suppliers must provide comprehensive Safety Data Sheets (SDS) and maintain appropriate documentation. In the United States, BOC-D-Pyroglutamic acid ethyl ester is intended for research and development use only and is not intended for therapeutic, food, cosmetic, or consumer applications unless explicitly stated otherwise. For pharmaceutical intermediate applications, manufacturers must comply with relevant FDA regulations and quality standards. The compound is not a controlled substance.

Transport information: BOC-D-Pyroglutamic acid ethyl ester is not classified as hazardous material for DOT/IATA transport purposes. Proper packaging, labeling, and documentation are nevertheless required for international shipping. The HS code for the compound is 2933.79.8500 (heterocyclic compounds with nitrogen hetero-atoms only).

Future Outlook

The market outlook for BOC-D-Pyroglutamic acid ethyl ester is positive, supported by several key growth drivers across its major application segments. While the compound remains a relatively specialized chiral building block, its orthogonally protected D-pyroglutamate scaffold and essential role in peptide synthesis and kinase inhibitor development position it for steady growth in the coming years. The global 1-Boc-D-Pyroglutamic Acid Ethyl Ester Reagent Market is forecast to maintain steady growth through 2028, driven by sustained demand from pharmaceutical, peptide synthesis, and fine chemical sectors.

Key growth drivers include:

1. Expansion of the peptide therapeutics market: The rapidly growing global market for peptide drugs—including GLP-1 receptor agonists, peptide antibiotics, and peptide-drug conjugates—drives demand for high-quality orthogonally protected chiral building blocks. BOC-D-Pyroglutamic acid ethyl ester is particularly valuable for introducing D-pyroglutamic acid residues into peptide sequences, which can enhance metabolic stability and biological activity.
2. Growth in kinase inhibitor development: The compound’s documented use in the synthesis of PF-06651600 (ritlecitinib) and other kinase inhibitors positions it at the forefront of targeted cancer and autoimmune disease therapy development. The growing pipeline of JAK inhibitors and other kinase-targeted therapeutics supports sustained demand for this key chiral intermediate.
3. Increasing focus on asymmetric synthesis and chiral drug development: The growing emphasis on stereochemically pure pharmaceutical compounds drives demand for enantiopure chiral building blocks. The compound’s ≥99% ee and defined (2R) stereochemistry make it an ideal platform for constructing complex chiral molecules with precise control over absolute configuration.
4. Expansion of pharmaceutical R&D in Asia: The growth of pharmaceutical R&D and API manufacturing in China and India—driven by increasing investment in generic drug production and innovative drug discovery—supports demand for high-quality chiral building blocks and pharmaceutical intermediates.
5. Growth in biochemical assay reagent applications: The compound’s utility as a biochemical assay reagent for studying enzymatic activities and protein interactions supports demand from academic and industrial research laboratories.

Challenges and considerations:

• Regulatory compliance: Increasingly stringent pharmaceutical and chemical regulations may require ongoing investment in quality systems and documentation.
• Stereochemical purity requirements: The specific requirement for the D-enantiomer (not the L-enantiomer or racemate) necessitates rigorous quality control and enantiomeric purity assurance.
• Limited scale: As a specialized chiral building block, the market for BOC-D-Pyroglutamic acid ethyl ester is smaller than that of commodity chemicals.
• Competition from alternative protecting groups: The market faces competition from Fmoc-protected pyroglutamate derivatives for certain peptide synthesis applications.
• Storage requirements: The compound requires storage at 2–8°C for long-term stability, which may increase handling and logistics costs.

To succeed in this evolving market landscape, suppliers must focus on product quality (particularly enantiomeric purity and batch-to-batch consistency), supply chain reliability, regulatory compliance, and responsive customer service. Companies that can offer high-purity products with comprehensive Certificates of Analysis (COA) documenting enantiomeric purity, flexible packaging options, and technical support for peptide synthesis, pharmaceutical development, and asymmetric synthesis applications will be well-positioned to capture growing demand.

Shanghai XinChem Co., Ltd. (XinChem)

As a world-leading supplier of organic chemicals and chiral building blocks, Shanghai XinChem Co., Ltd. (XinChem) is dedicated to meeting the innovative needs of the pharmaceutical, biotechnology, peptide synthesis, and fine chemical industries. Leveraging extensive experience and advanced manufacturing capabilities, XinChem provides high-quality BOC-D-Pyroglutamic Acid Ethyl Ester (CAS# 144978-35-8) 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 pharmaceutical companies, peptide synthesis laboratories, and research institutions seeking this versatile orthogonally protected chiral building block.

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 BOC-D-Pyroglutamic acid ethyl ester products. The production process incorporates established synthetic routes—including the Boc-protection of D-pyroglutamic acid ethyl ester using di-tert-butyl dicarbonate (Boc₂O) in the presence of 4-dimethylaminopyridine (DMAP) in acetonitrile, followed by purification via flash chromatography. This enables the delivery of products with purity ≥98% (HPLC) and ≥99% available to meet diverse application requirements. Strict process control ensures consistent enantiomeric purity ((2R)-configuration, ≥99% ee), minimal impurities, and batch-to-batch reproducibility, providing customers with reliable performance in peptide synthesis, pharmaceutical development, and asymmetric synthesis applications.

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 (HPLC/GC), specific optical rotation (+41.0°±2.0° in ethanol), water content (Karl Fischer ≤0.50%), melting point (54.0–58.0°C), and impurity profiles. XinChem offers batch-specific COA, customizable packaging, and globally compliant REACH, ISO 9001, and GMP-aligned manufacturing.

2. Product Advantages

High Purity and Consistent Quality
XinChem offers BOC-D-Pyroglutamic acid ethyl ester with purity ≥98% (HPLC) and ≥99% available, ensuring optimal performance in peptide synthesis, pharmaceutical development, and asymmetric synthesis. The product’s high purity and consistent enantiomeric configuration (≥99% ee) minimize the risk of unwanted side reactions and diastereomer contamination, making it suitable for demanding applications in drug discovery and peptide therapeutics. The product is available as a white to off-white crystalline powder with consistent appearance and defined melting point specifications.

Comprehensive Specifications
Key specifications include:

• Molecular Formula: C₁₂H₁₉NO₅
• Molecular Weight: 257.28–257.29 g/mol
• CAS Number: 144978-35-8
• Synonyms: Boc-D-Pyr-Oet; Ethyl N-(tert-Butoxycarbonyl)-D-pyroglutamate; (R)-1-tert-Butyl 2-ethyl 5-oxopyrrolidine-1,2-dicarboxylate; N-Boc-D-Pyroglutamic Acid Ethyl Ester
• MDL Number: MFCD09261329
• Appearance: White to off-white crystalline powder
• Purity: ≥98% (HPLC) / ≥99% available
• Enantiomeric Excess: ≥99% ee available
• Melting Point: 54.0–58.0°C
• Specific Optical Rotation: +44.0 to +47.0° (c=1, MeOH)
• Density: 1.182±0.06 g/cm³
• Boiling Point: 375.0±35.0°C at 760 mmHg
• Storage: 2–8°C, protect from light and moisture, sealed dry container
• GHS Classification: Warning; H315, H319, H335
• HS Code: 2933.79.8500

Flexible Packaging Solutions
XinChem provides a range of packaging options to accommodate diverse customer needs, from laboratory-scale quantities (1 g, 5 g, 10 g, 25 g) to industrial-scale packaging (100 g, 500 g, 1 kg, 25 kg drums) and bulk shipments. Customized packaging solutions are available upon request, ensuring safe handling, storage, and transportation with appropriate protection from light and moisture.

3. Application Fields

As a versatile orthogonally protected chiral building block, BOC-D-Pyroglutamic Acid Ethyl Ester (CAS# 144978-35-8) exhibits wide application value across multiple industries:

Peptide Synthesis and Peptidomimetics:

• Key building block for solid-phase peptide synthesis (SPPS) with orthogonal Boc/Fmoc strategies
• Enables precise formation of peptide bonds through EDC/HOBt or HATU coupling
• Substrate for the synthesis of various peptides and peptidomimetics
• Precursor for anticancer peptides and antimicrobial peptides
• Building block for peptides containing D-pyroglutamic acid residues with enhanced metabolic stability

Pharmaceutical Development and Drug Discovery:

• Key chiral intermediate for the synthesis of kinase inhibitors including PF-06651600 (ritlecitinib)
• Precursor for protease inhibitors and other therapeutic agents
• Building block for single-enantiomer drug development
• Intermediate for multi-step pharmaceutical synthesis requiring selective amine deprotection
• Precursor for prodrug development to mask carboxylic acids and improve membrane permeability

Biochemical Assay Reagents:

• Biochemical assay reagent for studying enzymatic activities and protein interactions
• Tool for investigating enzyme-substrate interactions and protein-ligand binding
• Reagent for chiral discrimination and enantioselective analysis

Asymmetric Synthesis and Chiral Building Blocks:

• Defined (2R)-configured chiral building block for stereoselective organic synthesis
• Platform for constructing complex chiral molecules with precise control over absolute configuration
• Orthogonal Boc/ethyl ester protection enables sequential deprotection in multi-step synthesis

4. Service Support

Technical Expertise and Customized Solutions
XinChem’s team of experienced chemists and pharmaceutical scientists provides full technical support throughout the customer journey—from product selection and specification development to application guidance and troubleshooting. Whether customers require optimization of peptide coupling conditions, guidance on orthogonal deprotection strategies, or assistance with regulatory documentation, XinChem’s technical experts are ready to help. Custom synthesis and contract manufacturing with flexible scaling from R&D to commercial quantities are available upon request.

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 appropriate temperature control (2–8°C) and moisture protection for product stability.

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, TSCA, and other regional regulations, helping customers navigate the complexities of global trade.

5. Reasons to Choose XinChem

• Professionalism: Extensive experience and deep expertise in chiral building block synthesis and supply.
• Quality: Rigorous quality control, high purity (≥98% to ≥99%), ≥99% ee, and adherence to international 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 including batch-specific COA.

Contact us today to start your partnership with XinChem!

Website: www.xinchem.com

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