73-03-0 Usage
Uses
Used in Pharmaceutical Industry:
Cordycepin is used as an immunomodulatory agent for improving immune function and as an anti-aging agent due to its ability to inhibit cell senescence via the activation of AMPK.
Used in Cancer Therapy:
Cordycepin is used as an anti-cancer agent for inducing apoptosis in various cancer cell lines and for its potential synergistic effects when combined with conventional chemotherapeutic drugs.
Used in Antiviral Applications:
Cordycepin is used as an anti-viral agent for its ability to inhibit viral replication and reduce viral load.
Used in Anti-inflammatory Applications:
Cordycepin is used as an anti-inflammatory agent for its ability to reduce inflammation and modulate inflammatory signaling pathways.
Used in Neuroprotection:
Cordycepin is used as a neuroprotective agent for its ability to inhibit Aβ-induced apoptosis in hippocampal neurons and protect against neurodegenerative diseases.
Used in Anti-obesity Applications:
Cordycepin is used as an anti-obesity agent for its ability to reduce body weight and improve metabolic parameters.
Used in Anti-fatigue Applications:
Cordycepin is used as an anti-fatigue agent for its ability to enhance physical endurance and reduce fatigue.
Used in Diabetes Management:
Cordycepin is used as a hypoglycemic agent for its ability to lower blood glucose levels and improve insulin sensitivity.
Used in Lipid-lowering Applications:
Cordycepin is used as a lipid-lowering agent for its ability to reduce blood lipid levels and improve cardiovascular health.
Used in Male Hormone Regulation:
Cordycepin is used as a male hormone regulator for its ability to modulate testosterone levels and improve male reproductive health.
Plant extracts
In 1951, German scientist Cunningham had purified a crystal from the Cordyceps militaris and named it cordycepin. From then on, the crordycepin reported in published literature abroad regarding to its antitumor, antiviral efficacy as well as extraction and purification had been all obtained from Cordyceps instead of being from Cordyceps sinensis which contains only trace amount of Cordycepin.
Cordyceps is the major active ingredient contained in Cordyceps (especially nucleoside). It belongs to a kind of nucleoside drugs, purine alkaloids and is also the first kind of nuclear glycosides antibiotics isolated from fungus. Owing to its special efficacy in repairing cells and protection of the genetic code of life, it has become one of the leaders in modern biomedicine. Cordycepin is a drug of natural source with various kinds of pharmacological effects such as anti-tumor, antibacterial and antiviral, immunomodulatory as well as free radical-scavenging, etc., and has good prospects for clinical application. At present time, the research on cordycepin present study is becoming an extremely active area in the field of pharmaceutical chemistry.
As a structural analogue of adenosine, cordycepin can inhibit Bacillus subtilis, Mycobacterium tuberculosis of birds and Ehrlich ascites tumor cells with inhibitory effect on the RNA and DNA synthesis inhibition of cancer cells, therefore having very strong inhibitory effect on the human nose and pharynx cancer (KD) cells. The clinically applied cordycepin is mostly used for adjuvant treatment of malignant tumors with the cases of improved clinical symptoms accounting for more than 91.7%; it is mainly used for the treatment of patients of nasal cancer, throat cancer, lung cancer, leukemia, brain cancer and other malignant tumor.
Cordycepin is extracted from the Cordyceps and is the mostly nutritious active substance inside Cordyceps. Its major composition is Cordyceps polysaccharide, Cordyceps acid as well as Cordyceps SOD and is a kind of natural nutrients of high health function. It can activate dormant cells, repair diseased cells, propagate the new living cells, clean up dead cells and is of great value in improving immunity, anti-fatigue as well as improving the body's energy.
Pharmacological effects
Most currently known Cordyceps fungus contains Cordycepin, which obviously plays an important role in the anti-tumor effect. Jagger believes the cordycepin contained in Cordyceps fungus can inhibit tumorigenesis through three possible mechanisms:
1. The free alcoholic group contained in cordycepin can be incorporated into the DNA of cancer cells and takes effect.
2. Cordycepin can inhibit the phosphorylation of nucleoside or nucleotide to generate the derivatives of diphosphate and triphosphate, thereby inhibiting the synthesis of nucleic acids in tumor cell.
3. Cordycepin can block the amination of xanthylic acid into guanylate.
In 1977, Müller et al found that cordycepin had strong inhibitory effect against the proliferation of L5718Y cell with the ED50 being 0.27μg; this inhibitory effect can be eliminated by adenosine but not 2'-deoxy-nucleosides; The tritium marked Cordyceps trial have showed that cordycepin can be incorporated into RNA rather than DNA. The cordycepin, inside the cell, can be phosphorylated to 3'-ATP; 3'-ATP has no effect on the activity of the DNA-dependent DNA polymerase α and β in L5718Y cells, but has strong inhibitory effect on the nuclear Poly (a) polysaccharide which will inevitably lead to a maturation defect of mRNA, further negatively affecting the formation of mRNA and protein synthesis. The anti-tumor effects of Cordyceps may be related to this mechanism. In 1997, the United States has applied cordycepin to third-period clinical trials for the treatment of pre-B and pre-T acute lymphocytic leukemia, while cordycepin also exhibit strong anti-fungal, anti-HIV viral and selective inhibition activity on the activity of Clostridium genus.
In 1985, with in vitro experiments, Jiang ping et al observed the cytotoxicity of Cordyceps sinensis and cultured mycelium (Qinghai) on ECA cells. For the treatment of in vitro cell culture ECA, the result showed that when they two were at the lowest effective concentration 0.405mg/ml and 25mg/ml, the total infection rate was 100%, 80%, respectively, indicating that the drug has different strengths of ECA cytotoxicity. Comprehensive in vivo tests speculated that the anti-tumor effect is correlated with the certain amount of 3'-deoxy-nucleosides contained in the drug and Cordyceps polysaccharides as well as the relative balance between the overall immune regulatory function of the drugs and its effect of maintaining body immunity. Cordyceps sinensis has certain cytotoxic effect, which is consistent with the report regarding to the strong cytotoxicity of cordycepin-resistant L1210.
The above information is edited by the lookchem of Dai Xiongfeng.
Biological Activity
Nucleoside analog that acts as an anticancer and antifungal agent. Can be converted to 3'-deoxyadenosine triphosphate (3'-dATP), which inhibits ATP-dependent DNA synthesis. Inhibits growth of various tumor cells in vitro .
Biochem/physiol Actions
Cordycepin is an adenosine analogue that is readily converted to cordycepin 5′-triphosphate; can be used for 3′-end labeling of RNA.
Purification Methods
3'-Deoxyadenosine forms needles from EtOH, n-BuOH and n-PrOH, and a monohydrate from H2O. It has max 260nm ( 14,600) in EtOH. The picrate has m 195o(dec, yellow crystals from H2O). [Kaczka et al. Biochim Biophys Acta 14 456 1964, Todd & Ulbricht J Chem Soc 3275 1960, Lee et al. J Am Chem Soc 83 1906 1961, Walton et al. J Am Chem Soc 86 2952 1964, Beilstein 26 III/IV 3594.]
References
1) Kim?et al. (2011),?Cordycepin blocks lung injury-associated inflammation and promotes BRCA1-deficient breast cancer cell killing by effectively inhibiting PARP; Mol. Med.?17?893
2) Kondrashov?et al.?(2012),?Inhibition of polyadenylation reduces inflammatory gene induction; RNA?18?2236
3)Yang?et al.?(2017),?Cordycepin inhibits LPS-induced inflammatory response by modulating NOD-Like Receptor Protein 3 inflammasome activation; Biomed. Pharmacother.?95?1777
4) Song?et al.?(2018),?Neuroprotective effects of cordycepin inhibit Aβ-induced apoptosis in hippocampal neurons; Neurotoxicology?68?73
5) Zhang?et al.?(2018),?Cordycepin induces apoptosis in human pancreatic cancer cells via the mitochondrial-mediated intrinsic pathway and suppresses tumor growth in vivo; OncoTargets Ther.?11?4479
6) Li?et al.?(2018),?Cordycepin modulates body weight by reducing prolactin via an adenosine A1 receptor; Curr. Pharm. Des.,?24?3240
7) Wang?et al?(2019)?Cordycepin prevents radiation ulcer by inhibiting cell senescence via NRF2 and SMPK in rodents;?Nat. Commun.?10?2538
8) Wang?et al.?(2020)?The novel application of cordycepin in maintaining stem cell pluripotency and increasing iPS cell generation efficiency; Sci. Rep.?10?2187
Check Digit Verification of cas no
The CAS Registry Mumber 73-03-0 includes 5 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 2 digits, 7 and 3 respectively; the second part has 2 digits, 0 and 3 respectively.
Calculate Digit Verification of CAS Registry Number 73-03:
(4*7)+(3*3)+(2*0)+(1*3)=40
40 % 10 = 0
So 73-03-0 is a valid CAS Registry Number.
73-03-0Relevant articles and documents
From adenosine to 3′-deoxyadenosine: Development and scale up
Aman, Sayed,Anderson, D. Jason,Connolly, Terrence J.,Crittall, Andrew J.,Ji, Guijun
, p. 601 - 605 (2000)
A manufacturing process has been developed suitable for the production of 3′-deoxyadenosine (cordycepin, 3′-dA) in 20% yield from adenosine. The chemistry involves conversion of adenosine to isomeric 2′,3′-bromoacetates with isolation of the desired isomer in high purity. Acidic hydrolysis followed by hydrogenolysis afforded product with a purity of ≥99%. Unlike routes reported in the literature, intermediates are isolated as solids, thus avoiding the use of chromatography for isomer separation and final product purification.
A NUCLEOSIDE DERIVATIVE FROM EMERICELLA NIDULANS
Kawahara, Nobuo,Sekita, Setsuko,Satake, Motoyoshi,Udagawa, Shun-Ichi
, p. 1409 - 1410 (1992)
5'-Acetyl-3'-deoxyadenosine, a new nucleoside derivative, has been isolated from Emericella nidulans var. lata, together with 3'-deoxyadenosine (cordycepin). Key Word Index: Emericella nidulans; Ascomycotina; fungus; nucleoside; 5'-acetyl-3'-deoxyadenosine; 3'-deoxyadenosine.
REGIOSPECIFIC AND STEREOSELECTIVE CONVERSION OF RIBONUCLEOSIDES TO 3-DEOXYNUCLEOSIDES. A HIGH YIELD THREE-STAGE SYNTHESIS OF CORDYCEPIN FROM ADENOSINE.
Hansske, Fritz,Robins, Morris J.
, p. 4295 - 4298 (1985)
Treatment of 2',3'-anhydroadenosine (obtained in 92percent yield from adenosine) with lithium triethylborohydride (or deuteride) gave cordycepin (or its 3'(R)-deuterio derivative) in 90percent overall yields with no 2'-deoxy isomer detected.
Synthesis method of cordycepin
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Paragraph 0022; 0023; 0033-0037, (2020/07/13)
The invention discloses a synthetic method for cordycepin. The method comprises the following steps: with adenosine as a starting material, subjecting adenosine and Mattock's bromide to bromination in a reaction solvent of acetonitrile and/or ethyl acetate during implementation of hydroxyl protection so as to obtain two products, i.e., 5'-[2,5,5-trimethyl-1,3-dioxolane-4-one-2-yl]-3'-bromo-3'-deoxy-2'-O-acetyl adenosine and 5'-[2,5,5-trimethyl-1,3-dioxolane-4-one-2-yl]-2'-bromo-2'-deoxy-3'-O-acetyl adenosine; then removing protective groups so as to obtain 3'-bromo-3'-deoxy-adenosine hydrochloride; and subjecting 3'-bromo-3'-deoxy-adenosine hydrochloride to debromination so as to obtain 3'-deoxyadenosine, i.e., cordycepin. The synthetic method provided by the invention is simple to operate, has short reaction steps and does not need purification in the process of reaction; and the purity and each index of the obtained cordycepin product are better than a currently commercially available cordycepin product.
ADENOSINE ANALOG AND ITS USE IN REGULATING THE CIRCADIAN CLOCK
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Paragraph 0113; 0126; 0127, (2018/08/12)
Provided are a kind of nucleoside analogue compounds, and compositions comprising these compounds and pentostatin, their use for modulating circadian rhythm, preferably, for shifting circadian phase, and methods for modulating circadian rhythm, preferably, for shifting circadian phase via these compounds or the compositions.
Preparation method of cordycepin
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Paragraph 0074-0078, (2018/11/03)
The invention discloses a preparation method of cordycepin. The preparation method comprises the following steps: a formula is shown in the description, wherein X is Cl or Br; R1 is one of the following groups: formulas are shown in the description; R2 is one of the following groups: formulas are shown in the description. The preparation method disclosed by the invention takes easy-to-obtain adenosine as a starting raw material and is simple to operate and convenient for purification and industrial large-scale production is easy to realize.
Phosphorus pentachloride promoted gem-dichlorination of 2′- and 3′-deoxynucleosides
Da Paixao Soares, Fabio,Groaz, Elisabetta,Herdewijn, Piet
, (2018/06/29)
Halogen substitution at various positions of canonical nucleosides has generated a number of bioactive structural variants. Herein, the synthesis of two unique series of sugar modified nucleosides bearing a gem-dichloro group is presented. The synthetic plan entails the controlled addition of phosphorus pentachloride to suitably protected 2′- or 3′-ketodeoxynucleoside intermediates as the key step, facilitating the rapid construction of such functionalized molecules. Under the same reaction conditions, the highest chemoselectivity was observed for the formation of 2′,2′-dichloro-2′,3′-dideoxynucleosides, while a competing 2′,3′-elimination process occurred in the case of the 3′,3′-dichloro counterparts.
An effective and convenient synthesis of cordycepin from adenosine
Huang, Shen,Liu, Hui,Sun, Yanhua,Chen, Jian,Li, Xiufang,Xu, Jiangfeng,Hu, Yuwei,Li, Yuqing,Deng, Zhiwei,Zhong, Shian
, p. 149 - 160 (2018/01/17)
Cordycepin is a purine nucleoside analog with potent and diverse biological activities. Herein, we designed two methods to synthesize cordycepin. One method mainly converted the 3′-OH group into an iodide group and further dehalogenation to yield the final product. Although this method presented a short synthetic procedure, the synthesis had a low overall yield, resulting in only 13.5% overall yield. To improve the overall yield of cordycepin, another synthetic route was studied, which consisted of four individual steps: (1) 5′-OH protection (2) esterification (3) -O-tosyl (-OTs) group removal (4) deprotection. The key step in the synthetic method involved the conversion of 5′-O-triphenylmethyladenosine to 3′-O-tosyl-5′-O-triphenylmethyladenosine, using LiAlH4 as reducing agent. The main advantages of this route were an acceptable total product yield and the commercial availability of all starting materials. The optimal reaction conditions for each step of the route were identified. The overall yield of cordycepin obtained from adenosine as the starting material was 36%.
Modified nucleosides for the treatment of viral infections and abnormal cellular proliferation
-
, (2018/11/10)
The disclosed invention is a composition for and a method of seating a Flaviviridae (including BVDV and HCV), Orthomyxoviridae (including Influenza A and B) or Paramyxoviridae (including RSV) infection, or conditions related to abnormal cellular proliferation, in a host, including animals, and especially humans, using a nucleoside of general formula (I)-(XXIII) or its pharmaceutically acceptable salt or prodrug. This invention also provides an effective process to quantify the viral load, and in particular BVDV, HCV or West Nile Virus load, in a host, using real-time polymerase chain reaction (“RT-PCR”). Additionally, the invention discloses probe molecules that can fluoresce proportionally to the amount of virus present in a sample.
Synthetic method for 3-deoxyadenosine and product thereof, and application of product
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Paragraph 0019, (2017/05/27)
The invention relates to a synthetic method for compound, especially to a synthetic method for 3-deoxyadenosine and a product thereof, and application of the product. The synthetic method comprises the following steps: (1) halogenation of adenosine: with tetraacetoxysilane as a halogenation catalyst, synthesizing 3(2)-deoxy-3(2)-halogeno-2(3),5-di(O-acetyl)adenosine from a system consisting of phosphorus trichloride and tetraacetoxysilane; (2) recrystallization and purification: carrying out purification and separation by using absolute ethyl alcohol so as to obtain a pure 3(2)-deoxy-3(2)-halogeno-2(3),5-di(O-acetyl)adenosine crystal; and (3) catalytic hydrogenation: carrying out catalytic hydrogenation so as to obtain 3-deoxyadenosine. According to the invention, 3(2)-deoxy-3(2)-halogeno-2(3),5-di(O-acetyl)adenosine is obtained through selection of an appropriate halogenation reagent, and cyclization and ring-opening reactions are avoided, so procedures are reduced and cost is lowered; and 3-deoxyadenosine with high purity is prepared.
