CAS number 949023-16-9
EINECS number 1592732-453-0
Chemical formula C₂₄H₂₁NO₅
molecular weight 403.43
InChIKey RDVJYGYJBUIIOE-ZOAFEQKISA-N
Density 1.291 g/cm³
Boiling Point 642.3±55.0 °C at 760 mmHg (Predicted)
Flash Point 342.2±31.5 °C
Water Solubility: Slightly soluble in water; soluble in organic solvents such as methanol, ethanol, DMSO, and dichloromethane
Vapor Pressure 0.0±2.0 mmHg at 25°C
Refractive Index 1.624
Storage Conditions: Sealed in dry, room temperature; recommended protection from light and inert gases.
Sensitivity: Sensitive to humidity and air; requires protection from moisture and light.
Appearance: White to off-white solid
Specific Gravity 1.291
Color: White to off-white
MDL Number MFCD11617943
Hazard Symbol No specific GHS pictogram (based on available data)
Risk term H302 (Harmful if ingested)
Safety term P280 (Wear protective gloves/eye protection/face protection); P305+P351+P338 (If in eyes: Rinse carefully with water for several minutes)
Customs code 29349990 (Other heterocyclic compounds, refer to classification)
II. Properties
Paclitaxel side chain (CAS: 949023-16-9) is a chiral compound containing a five-membered ring structure of oxazolidine, with two chiral centers (4S, 5R configuration). This compound belongs to the key chiral intermediates of taxane antitumor drugs, and its structure contains multiple aromatic substituents such as benzoyl, p-methoxyphenyl, and phenyl, as well as a carboxylic acid functional group.
Physical properties: Appearance: White to off-white crystalline solid, odorless. Density: Approximately 1.291 g/cm³, classifying it as a medium-density organic compound. Predicted boiling point: High as 642.3°C (760 mmHg), indicating excellent thermal stability. Flash point: 342.2°C, not classified as a flammable hazardous material. Vapor pressure at 25°C: Extremely low (0.0 ± 2.0). (mmHg), almost non-volatile; refractive index 1.624, exhibiting high optical density; chemical properties: contains a carboxylic acid group (-COOH), exhibiting acidity, with a predicted pKa of 2.85±0.60; contains an amide bond (-N-CO-), which can undergo hydrolysis under strong acid or strong base conditions; the oxazolidine ring can open under acidic conditions, a key reaction site in the semi-synthesis of paclitaxel; relatively stable to light, heat, and oxidants, but prolonged exposure to humid environments may lead to degradation; can undergo esterification, amidation, and other conventional carboxylic acid derivative reactions.
III. Uses: The paclitaxel side chain is a core chiral intermediate in the synthesis of paclitaxel (trade name Taxol) and its derivatives (such as docetaxel/docetaxel). Paclitaxel is widely used as a first-line antitumor drug in the treatment of various malignant tumors, including ovarian cancer, breast cancer, non-small cell lung cancer, head and neck cancer, gastric cancer, and melanoma. Main Application Areas: Semi-synthetic Paclitaxel API Production: Linked with the 10-deacetylated baccatin III (10-DAB) or baccatin III core via esterification to form the complete paclitaxel molecule. The (4S,5R) absolute configuration of the side chain directly determines the final drug’s bioactivity and safety. Docetaxel Synthesis: Used as a precursor or analog of docetaxel side chain for the synthesis of docetaxel and its derivatives. Docetaxel is a second-generation semi-synthetic analog of paclitaxel, offering superior efficacy and a different toxicity spectrum. Paclitaxel Drug Development: Used for the synthesis of novel paclitaxel derivatives, prodrugs, and targeted formulations. Supports the development of high-end formulations such as nano-formulations, albumin-bound paclitaxel (Abraxane), and liposomal formulations. Used for the synthesis of polymeric conjugates (such as dextran-paclitaxel conjugates) to improve water solubility and targeting. Drug Analysis and Quality Control: Used as a standard and impurity reference. 68) Used for quality research of paclitaxel raw materials and formulations
Used for the development of analytical methods such as HPLC and LC-MS
Scientific research and biotechnology
Used for research on the biosynthetic pathway of paclitaxel
Supporting research on synthetic biology and metabolic engineering
IV. Preparation Method The synthesis of paclitaxel side chains belongs to high-value-added fine organic synthesis, involving multiple steps and strict chiral control. Currently, the following synthetic strategies are mainly used industrially:
4.1 Chemical Synthesis (Mainstream Process)
Route 1: Starting from (2R,3S)-3-phenylisoserine
Esterification: Using (2R,3S)-3-phenylisoserine hydrochloride as a starting material, esterification occurs in a methanol/thionyl chloride system to generate (2R,3S)-phenylisoserine methyl ester.
Benzoylation: Reaction with benzoyl chloride under alkaline conditions introduces an N-benzoyl protecting group, yielding (2R,3S)-N-benzoyl-phenylisoserine methyl ester.
Cycloprotection: Condensation cyclization occurs with p-methoxybenzaldehyde under acidic conditions to construct an oxazolidine five-membered ring skeleton, generating (4S,5R)-5-methoxycarbonyl-2-(4-methoxyphenyl)-4-phenyl-3-benzoyl-1,3-oxazolidine.
Hydrolysis : Hydrolyze the methyl ester group under mild alkaline conditions to obtain crude paclitaxel side chain.
Purification: Purify by recrystallization (e.g., ethyl acetate/n-hexane system) or column chromatography to obtain a high-purity (≥98%) product.
Route Two: Asymmetric Catalytic Synthesis
Construct chiral centers using Sharpless asymmetric bihydroxylation, asymmetric hydroxylation, or asymmetric Mannich reaction.
Use chiral catalysts (e.g., DHQ-PHAL, Mn-salen complexes, chiral phosphate/rhodium acetate system) to control stereoselectivity.
Obtain chiral intermediates with high ee values (>99%) through kinetic resolution or substrate-controlled strategies.
Route Three: β-Lactam Method (Ojima-Holton Method)
Use β-lactam synthons (β-Lactam…) Direct coupling of paclitaxel with the bacardine III nucleus.
Developed by Ojima et al., this method is a classic industrial method for the semi-synthetic synthesis of paclitaxel.
4.2 Biosynthetic Method (Emerging Technology)
Side chain precursors are synthesized using Taxus cell culture or microbial heterologous expression systems (such as E. coli and Saccharomyces cerevisiae).
α-phenylalanine is converted to β-phenylalanine via PAM (phenylalanine aminotransferase), followed by side chain linkage catalyzed by enzymes such as BAPT (bacardine III-phenylalanine aminotransferase).
Synthetic biology strategy: Reconstructing the paclitaxel biosynthetic pathway, optimizing precursor supply, and engineering the rate-limiting enzyme.
4.3 Key Process Control Points
Chiral Purity Control: EE value is monitored using chiral HPLC to ensure (4S, 5R) configuration uniformity.
Moisture Control: Anhydrous operation throughout the process to prevent oxazolidine ring opening and feedstock hydrolysis.
Temperature Control: Cyclization reactions are typically carried out at 0°C to room temperature to avoid side reactions.
Heavy Metal Residues: Catalysts (such as Pd/C, rhodium complexes) must be strictly removed, complying with ICH Q3D standards.
V. Safety Information
5.1 Hazard Overview
Based on existing GHS classification data, the main hazards of paclitaxel side chains are:
Health Hazards: H3O2 (harmful if ingested), may cause irritation to the digestive system.
Physical Hazards: Not a flammable liquid (flash point > 300°C), non-explosive.
Environmental Hazards: No specific aquatic toxicity data available; disposal according to organic chemical regulations is recommended.
5.2 First Aid Measures
Inhalation: Move the patient to fresh air, keep the airway open, and seek medical attention if necessary.
Skin Contact: Immediately remove contaminated clothing and wash with plenty of water and soap for at least 15 minutes.
Eye Contact: Immediately lift eyelids and flush with running water or saline solution for at least 15 minutes (P305+P351+P338).
Ingestion: Do not induce vomiting. Rinse mouth immediately and drink plenty of warm water. Carry the product label and seek medical attention.
5.3 Firefighting Measures
Applicable Extinguishing Agents: Dry powder, carbon dioxide, foam, or sand.
Contraindicated Extinguishing Agents: No specific contraindications.
Firefighter Protection: Wear self-contained breathing apparatus and full protective clothing.
Combustion Products: May produce toxic fumes such as nitrogen oxides and carbon oxides.
5.4 Leakage Emergency Handling
Personal Protection: Wear protective gloves, goggles, and a dust mask (P280)
Environmental Protection: Prevent leaked material from entering sewers, surface water, and groundwater.
Cleanup Methods: Collect with inert absorbent materials (such as sand or vermiculite) and transfer to a sealed container for hazardous waste disposal.
Large Leaks: Construct dikes or dig pits to contain the spill; contact a professional hazardous waste disposal organization.
5.5 Handling and Storage
Handling Precautions: Operate in a well-ventilated area to avoid dust generation; operators must be specially trained.
Storage Conditions: Store in a sealed, dry place at room temperature; nitrogen purging is recommended; store in a cool, dark place.
Incompatible Materials: Strong oxidizers, strong alkalis, strong acids
Shelf Life: Under recommended storage conditions, the shelf life is typically 2-3 years.
5.6 Exposure Controls/Personal Protection
Engineering Controls: Local exhaust ventilation or general ventilation system
Respiratory Protection: N95/KN95 dust mask or half-face respirator
Eye Protection: Chemical safety goggles or face shield
Body Protection: Impermeable work clothes and chemical-resistant gloves
Other: Eating and smoking are prohibited at the work site; thorough washing is required after work.
5.7 Toxicological Information
Acute Toxicity: No publicly available LD50 data; classified as low acute toxicity according to H3O2.
Irritation: May cause mild irritation to eyes, skin, and respiratory tract.
Sensitization: No known sensitization reports.
Carcinogenicity: No carcinogenicity data for this compound are available from IARC, NTP, or OSHA.
5.8 Ecological Information
Ecotoxicity: May be harmful to aquatic organisms; avoid direct release into the environment.
Biodegradability: Expected to be poorly biodegradable; moderately persistent.
Bioaccumulation: LogP = 3.59; moderately lipid-soluble; may have some bioaccumulation potential.
5.9 Waste Disposal
Waste Type: Hazardous waste (HW02 pharmaceutical waste or HW06 organic solvent waste)
Disposal Method: Incinerated by a qualified hazardous waste treatment facility
Packaging Disposal: Cleaned or incinerated according to hazardous waste packaging management requirements
5.10 Transportation Information
UN Number: No specific UN number (non-hazardous)
Packaging Category: Packaged as general chemicals or pharmaceutical intermediates
Transportation Precautions: Avoid mixing with food and feed; prevent exposure to sunlight, rain, and packaging damage
VI. Our Company’s Production Advantages and Capacity
6.1 Core Competitive Advantages
1. Advanced Synthesis Technology
Our independently developed multi-step continuous flow synthesis technology boasts high reaction selectivity and few byproducts.
Our proprietary cyclization-protection-hydrolysis integrated process increases the overall yield by 15-20% compared to the industry average.
2. Strict Quality System
We are ISO 9001 quality management system certified and comply with ICH standards. Q7 GMP Guidelines for Active Pharmaceutical Ingredients: COA (Certificate of Assessment) for each batch of product, including full testing items such as chiral purity, chemical purity, residual solvents, heavy metals, and moisture. Supports customer and third-party audits; data integrity complies with ALCOA+ principles.
3. Comprehensive Registration Support:Available DMF/CEP/ASMF and other registration application support documents.Complete Process Validation and Cleaning Validation data packages.Detailed Impurity Profile and Genotoxic Impurity (GTI) Assessment Reports. Complies with major pharmaceutical regulations such as FDA, EMA, and NMPA.
4. Flexible Customization Services:Supports customized production from gram to ton scale.Products with different crystal forms and particle size distributions can be provided according to customer needs.Custom synthesis of stable isotope markers (such as ¹³C and ²H markers) and impurity reference standards.Professional technical team provides full technical support from route design to scale-up production.
5. Supply Chain Security: Long-term agreements have been signed with strategic suppliers for key starting materials (such as (2R,3S)-3-phenylisoserine) to ensure supply chain stability. A dual-supplier system has been established to reduce the risk of relying on a single source.
Post time: May-19-2026
