Camptothecin

Base Information

• Chemical Name: Camptothecin
• CAS No.: 7689-03-4
• Deprecated CAS: 157405-40-8
• Molecular Formula: C20H16N2O4
• Molecular Weight: 348.358
• Hs Code.: 29399990
• European Community (EC) Number: 444-280-6,616-407-7
• NSC Number: 94600
• UNII: XT3Z54Z28A
• DSSTox Substance ID: DTXSID0030956
• Nikkaji Number: J2.266G
• Wikipedia: Camptothecin
• Wikidata: Q419964
• NCI Thesaurus Code: C338
• Pharos Ligand ID: QLD741VZ26ZW
• Metabolomics Workbench ID: 51406
• ChEMBL ID: CHEMBL65
• Mol file: 7689-03-4.mol

Synonyms:Camptothecin;Camptothecine

Chemical Property of Camptothecin

Chemical Property:

• Appearance/Colour: light yellow crystal powder
• Vapor Pressure: 3.74E-19mmHg at 25°C
• Melting Point: 260 °C (dec.)(lit.)
• Refractive Index: 1.787
• Boiling Point: 757.01 °C at 760 mmHg
• PKA: pKa 10.83 (Uncertain)
• Flash Point: 411.625 °C
• PSA: 81.42000
• Density: 1.513 g/cm³
• LogP: 2.07960
• Storage Temp.: 2-8°C
• Solubility.: chloroform/methanol (4:1): 4 mg/mL
• Water Solubility.: insoluble
• XLogP3: 1
• Hydrogen Bond Donor Count: 1
• Hydrogen Bond Acceptor Count: 5
• Rotatable Bond Count: 1
• Exact Mass: 348.11100700
• Heavy Atom Count: 26
• Complexity: 742

Purity/Quality:

98%, 99% ^*data from raw suppliers

Camptothecin ^*data from reagent suppliers

Safty Information:

• Pictogram(s): T, Xn, Xi
• Hazard Codes: T,Xi,Xn
• Statements: 36/37/38-25-20/21/22
• Safety Statements: 45-36/37/39-26-36

MSDS Files:

SDS file from LookChem

Useful:

• Canonical SMILES: CCC1(C2=C(COC1=O)C(=O)N3CC4=CC5=CC=CC=C5N=C4C3=C2)O
• Isomeric SMILES: CC[C@@]1(C2=C(COC1=O)C(=O)N3CC4=CC5=CC=CC=C5N=C4C3=C2)O
• Description: Camptothecin is an alkaloid derived from Xi Shu (Camptotheca acuminata), which belongs to Nyssaceae. The traditional Chinese medicine Camptotheca acuminata (Xi Shu) has been collected in the Compilation of Chinese Herbal Medicine, Chinese Materia Medica, and Great Dictionary of Chinese Medicine. Camptotheca acuminata (Xi Shu) is widely distributed in the basin of Yangtze river and the southwestern provinces. The main medicinal parts of Camptotheca acuminata (Xi Shu) are root bark and fruit, which get rid of heat and toxic materials and eliminate the disease. DNA topoisomerases relax DNA torsional strain created during replication, transcription, recombination, repair, and chromosome condensation. The relaxation of DNA supercoiling by topoisomerase I at single-strand breaks enables anticancer agents to reversibly trap the complex by intercalating between DNA base pairs at the cleavage site, thus inhibiting religa Camptothecin is a cytotoxic, quinoline alkaloid, discovered as the active principle of extracts from the Chinese tree C. acuminate, that inhibits the DNA enzyme topoisomerase I (Top1). It binds the Top1-DNA cleavage complex, inducing DNA-strand breaks. Camptothecin has strong anti-tumor activity against a wide range of experimental tumors and inhibits both DNA and RNA synthesis in mammalian cells. It displays cytotoxity in HT-29 cells with an IC50 value of 10 nM and induces DNA damage at concentrations as low as 51 nM in whole cells and 12 nM in isolated nuclei in in vitro assays.
• Physical properties: Appearance: pale yellow needlelike crystal. Solubility: slightly soluble in ethanol and chloroform; poorly soluble in water; camptothecin fails to generate stable salt with acid, whereas it can produce sodium salt which is soluble in water by reacting with heated sodium hydroxide solution. Melting point: 264–267?°C. Camptothecin derivatives
• Uses: antineoplastic Antitumor agent;Topoisomerase I inhibitor 10-hydroxycamptothecine precursor, topoisomerase inhibitor, binds irreversibly to DNA-topoisomerase I complex
• Indications: It is mainly used in digestive tract tumors and has a good effect on gastric cancer, rectal cancer, and colon cancer. Besides, it can improve the surgical resection of advanced gastric cancer and also has some therapeutic effect on bladder cancer and lung adenocarcinoma. Moreover, camptothecin can be used for treatment of psoriasis, warts, acute and chronic leukemia, and hepatosplenomegaly caused by schistosomiasis.
• Clinical Use: Because of the toxicity and side effects of camptothecin, the currently used agents in clinical applications are camptothecin derivatives like topotecan, irinotecan, and hydroxycamptothecin. Topotecan, a water-soluble camptothecin derivative developed by SmithKline Beecham, was approved by FDA in 1996 for the treatment of ovarian cancer. As another water-soluble camptothecin derivative approved by FDA in 1996, irinotecan was mainly used in the treatment of advanced colorectal cancer. In addition, it was also shown to have obvious inhibitory effect on small cell lung cancer and leukemia. Hydroxycamptothecin possesses a broad-spectrum antitumor activity and was clinically used for intravesical therapy of bladder cancer. In addition, it has remarkable curative effect on colon cancer, breast cancer, gastric cancer, and leukemia.

Technology Process of Camptothecin

There total 250 articles about Camptothecin 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: 84.4%

(E)-N-(2-aminobenzylidene)-4-methylaniline (55857-35-7) + (4S)-4-ethyl-7,8-dihydro-4-hydroxy-1H-pyrano[3,4-f]indolizine-3,6,10(4H)-trione (110351-94-5) → camptothecin (7689-03-4,91926-09-9)

Guidance literature:

With toluene-4-sulfonic acid; In toluene; Heating; 1) 30 min, 2) 3 h;

Reference yield: 83.0%

4-ethyl-1,12-dihydro-14H-pyrano[3',4':6,7indolizino[1,2-b]]quinolin-14-one (841276-70-8) → camptothecin (7689-03-4,91926-09-9)

Guidance literature:

4-ethyl-1,12-dihydro-14H-pyrano[3',4':6,7indolizino[1,2-b]]quinolin-14-one; With potassium osmate; hydroquinindine-2,5-diphenyl-4,6-pyrimidinediyl diether; methanesulfonamide; potassium carbonate; potassium hexacyanoferrate(III); In water; tert-butyl alcohol; at 0 ℃;

With iodine; calcium carbonate; In methanol; water; at 40 ℃;

DOI:10.1002/asia.201403190

Reference yield: 80.0%

formaldehyd (50-00-0,30525-89-4,61233-19-0) + 7-((2R,4S)-2-tert-butyl-4-ethyl-5-oxo-1,3-dioxolan-4-yl)indolizino[1,2-b]quinolin-9(11H)-one → camptothecin (7689-03-4,91926-09-9)

Guidance literature:

With hydrogenchloride; acetic acid; In 1,4-dioxane; water; at 90 ℃; for 19h;

DOI:10.1016/j.tet.2019.03.028

upstream raw materials:

camtothecin-20-O-methyl carbonate

(E)-N-(2-aminobenzylidene)-4-methylaniline

(4S)-4-ethyl-7,8-dihydro-4-hydroxy-1H-pyrano[3,4-f]indolizine-3,6,10(4H)-trione

9-amino-20(S)-camptothecin

Downstream raw materials:

7-Benzylcamptothecin

7-ethylcamptothecin

(S)-10-hydroxycamptothecin

(S)-9-acetoxy-4-ethyl-4-hydroxy-1,12-dihydro-4H-pyrano[3',4':6,7]indolizino[1,2-b]quinoline-3,14-dione

Refernces

• 1、 Comins, Daniel L.,Nolan, Jason M.. "A practical six-step synthesis of (S)-camptothecin". . p. 4255 - 4257. Retrieved 2001.
• 2、 Zheng, Chao,Li, Ming-Zong,You, Tian-Pa,Tang, Wei-Ping,Lou, Li-Guang. "Synthesis and antitumor activity of a series of lactone-opened camptothecin derivatives". . p. 51 - 61. Retrieved 2019.
• 3、 Song, Lin,Bevins, Robert,Anderson, Bradley D.. "Kinetics and mechanisms of activation of α-amino acid ester prodrugs of camptothecins". . p. 4344 - 4355. Retrieved 2006.
• 4、 Aiyama, Ritsuo,Nagai, Hisako,Nokata, Kenichiro,Shinohara, Chigiru,Sawada, Seigo. "A CAMPTOTHECIN DERIVATIVE FROM NOTHAPODYTES FOETIDA". . p. 3663 - 3664. Retrieved 1988.
• 5、 Liu, Jun,Wang, Jinhua,Si, Shuang,Xu, Jinyi,Xue, Peng. "Hydrogean Peroxide Inducible Acid-Activatable Prodrug for Targeted Cancer Treatment". . p. 3231 - 3235. Retrieved 2021.