Docetaxel

Base Information

• Chemical Name: Docetaxel
• CAS No.: 114977-28-5
• Deprecated CAS: 129522-72-1,216252-50-5,216252-50-5
• Molecular Formula: C₄₃H₅₃NO₁₄
• Molecular Weight: 807.892
• Hs Code.: 2932999099
• European Community (EC) Number: 601-339-2
• NSC Number: 628503
• UNII: 699121PHCA
• DSSTox Substance ID: DTXSID0040464
• Nikkaji Number: J314.049K
• Wikipedia: Docetaxel
• Wikidata: Q420436
• NCI Thesaurus Code: C61734
• RXCUI: 1299922
• Pharos Ligand ID: UHFR3MZHPXJJ
• Metabolomics Workbench ID: 43456
• ChEMBL ID: CHEMBL92
• Mol file: 114977-28-5.mol

Synonyms:docetaxel;docetaxel anhydrous;docetaxel hydrate;docetaxel trihydrate;docetaxol;N Debenzoyl N tert butoxycarbonyl 10 deacetyltaxol;N-debenzoyl-N-tert-butoxycarbonyl-10-deacetyltaxol;NSC 628503;RP 56976;RP-56976;RP56976;Taxoltere metro;Taxotere

Chemical Property of Docetaxel

Chemical Property:

• Appearance/Colour: Off-white Cryst
• Melting Point: 232 °C
• Refractive Index: 1.618
• Boiling Point: 900.5 °C at 760 mmHg
• Flash Point: 498.4 °C
• PSA: 224.45000
• Density: 1.37 g/cm³
• LogP: 3.65050
• XLogP3: 1.6
• Hydrogen Bond Donor Count: 5
• Hydrogen Bond Acceptor Count: 14
• Rotatable Bond Count: 13
• Exact Mass: 807.34660536
• Heavy Atom Count: 58
• Complexity: 1660

Purity/Quality:

98.0~102.0% ^*data from raw suppliers

Safty Information:

• Pictogram(s): Xi
• Hazard Codes: Xi

MSDS Files:

SDS file from LookChem

Useful:

• Drug Classes: Antineoplastic Agents
• Canonical SMILES: CC1=C2C(C(=O)C3(C(CC4C(C3C(C(C2(C)C)(CC1OC(=O)C(C(C5=CC=CC=C5)NC(=O)OC(C)(C)C)O)O)OC(=O)C6=CC=CC=C6)(CO4)OC(=O)C)O)C)O
• Isomeric SMILES: CC1=C2[C@H](C(=O)[C@@]3([C@H](C[C@@H]4[C@]([C@H]3[C@@H]([C@@](C2(C)C)(C[C@@H]1OC(=O)[C@@H]([C@H](C5=CC=CC=C5)NC(=O)OC(C)(C)C)O)O)OC(=O)C6=CC=CC=C6)(CO4)OC(=O)C)O)C)O
• Recent ClinicalTrials: Study in Participants With Early-Stage or Locally Advanced Human Epidermal Growth Factor Receptor (HER) 2-Positive Breast Cancer to Evaluate Treatment With Trastuzumab Plus (+) Pertuzumab + Docetaxel Compared With Trastuzumab + Placebo + Docetaxel
• Recent EU Clinical Trials: NeoAdjuvant Dynamic marker - Adjusted Personalized Therapy comparing trastuzumab-deruxtecan versus pacli-/docetaxel+carboplatin+trastuzumab+pertuzumab in HER2+ early breast cancer
• Recent NIPH Clinical Trials: Phase II trial of docetaxel/pembrolizumab in head and neck squamous cell carcinoma
• Chemical Properties and Classification: Docetaxel is a taxane derivative used as a chemotherapeutic drug. Its chemical formula is C43H53NO14, and it belongs to the class of plant alkaloids. It is found crystalline and is commonly prescribed for various malignancies.
• Therapeutic Uses: Docetaxel has been utilized in the treatment of several cancers, including non-small lung cancer, ovarian cancer, triple-negative breast cancer, and metastatic prostate cancer. It acts as a microtubule inhibitor, leading to cell cycle arrest at the G2/M phase and induction of apoptosis.
• Challenges in Drug Delivery: Docetaxel exhibits poor permeability and aqueous solubility, resulting in low oral absorption and bioavailability. It is a substrate for the drug efflux pump P-glycoprotein (P-gp), leading to rapid clearance and drug resistance.
• Enhancing Solubility and Delivery: Common solubility agents like Cremophor EL and Tween80 are employed to enhance the solubility of poorly water-soluble anticancer agents. The development of drug delivery systems is essential to enhance the uptake and accumulation of docetaxel, thereby improving therapeutic efficacy at lower doses.
• Metabolism and Transport: Docetaxel is susceptible to metabolism by enzymes belonging to the cytochrome P450 family. It interacts with transport proteins, with P-glycoprotein being responsible for the majority of its transportation across cellular membranes.
• Recent Developments: The addition of darolutamide, an androgen receptor signaling inhibitor, to therapy with docetaxel has been approved for treating metastatic prostate cancer. Clinical trials are ongoing to investigate the efficacy of darolutamide combined with androgen deprivation therapy (ADT) and docetaxel or cabazitaxel in metastatic castration-resistant prostate cancer patients.

Technology Process of Docetaxel

There total 133 articles about Docetaxel which guide to synthetic route it. The literature collected by LookChem mainly comes from the sharing of users and the free literature resources found by Internet computing technology. We keep the original model of the professional version of literature to make it easier and faster for users to retrieve and use. At the same time, we analyze and calculate the most feasible synthesis route with the highest yield for your reference as below:

synthetic route:

Reference yield: 100.0%

di-tert-butyl dicarbonate (24424-99-5) + (2aR,4S,4aS,6R,9S,11S,12S,12aR,12bS)-12b-acetoxy-9-(((2R,3S)-3-amino-2-hydroxy-3-phenylpropanoyl)oxy)-4,6,11-trihydroxy-4a,8,13,13-tetramethyl-5-oxo-2a,3,4,4a,5,6,9,10,11,12,12a,12b-dodecahydro-1H-7,11-methanocyclodeca[3,4]benzo[1,2-b]oxet-12-yl benzoate (133524-69-3,133577-36-3,133577-37-4) → Docetaxel (114915-20-7,114977-28-5,114977-29-6,133577-32-9,133577-33-0)

Guidance literature:

Reference yield: 92.8%

2'-acetyldocetaxel (151509-27-2) → Docetaxel (114915-20-7,114977-28-5,114977-29-6,133577-32-9,133577-33-0)

Guidance literature:

With dihydrogen peroxide; sodium hydrogencarbonate; In tetrahydrofuran; water; at 20 ℃;

DOI:10.1002/cjoc.201201142

Reference yield: 90.0%

7,10-bis-O-(2,2,2-trichloroethoxycarbonyl)docetaxel (114915-14-9) → Docetaxel (114915-20-7,114977-28-5,114977-29-6,133577-32-9,133577-33-0)

Guidance literature:

With acetic acid; zinc; In methanol; at 60 ℃; for 2h;

DOI:10.1016/S0040-4020(01)81313-2

upstream raw materials:

di-tert-butyl dicarbonate

C₃₈H₄₅NO₁₂

7,10-di(2,2,2-trichloroethyloxy-carbonyl)-13-cinnamoyl-10-deacetyl baccatin III

(2aR,4S,4aS,6R,9S,11S,12S,12aR,12bS)-12b-acetoxy-9-(((2R,3S)-3-amino-2-hydroxy-3-phenylpropanoyl)oxy)-4,6,11-trihydroxy-4a,8,13,13-tetramethyl-5-oxo-2a,3,4,4a,5,6,9,10,11,12,12a,12b-dodecahydro-1H-7,11-methanocyclodeca[3,4]benzo[1,2-b]oxet-12-yl benzoate

Downstream raw materials:

2',10-bis-O-(2,2,2-trichloroethoxycarbonyl)docetaxel

docetaxel/mono propylene glycol clathrate

C₄₇H₆₃NO₁₄Si

C₅₃H₇₅NO₁₄Si

Refernces

• 1、 Xue, Baoyu,Zhao, Junhong,Fan, Yange,Chen, Shipeng,Li, Wenfeng,Chen, Jin,Li, Zheng,Wang, Hongxing,Kong, Hongjun. "Synthesis of Taxol and Docetaxel by Using 10-Deacetyl-7-xylosyltaxanes". . . Retrieved 2020/02/05.
• 2、 -. "Method for synthesizing cabazitaxel from 10-deacetylbaccatin III". . . Retrieved 2019/09/17.