ICARITIN

Icaritin;  118525-40-9; AC1NSXIV; UNII-UFE666UELY;

3,5,7-trihydroxy-2-(4-methoxyphenyl)-8-(3-methylbut-2-enyl)chromen-4-one

3,5,7-trihydroxy-2-(4-methoxyphenyl)-8-(3-methylbut-2-enyl)chromen-4-one

C21H20O6
Molecular Weight:	368.3799 g/mol

The roots of Epimedium brevicornu Maxim

  

Beijing Shenogen Granted Fast Track Status for Novel Cancer Drug 

Written by Richard Daverman, PhD, Executive Editor, Greg B. Scott.

Beijing Shenogen Biomedical announced that Icaritin, a China Class I cancer drug, was granted Fast Track Review status after the company filed its New Drug Approval submission to the Beijing Food & Drug Administration. Icaritin is an oral traditional Chinese medicine, derived from barrenwort, which targets the estrogen receptor α36. Shenogen has conducted clinical trials of Icaritin in patients with liver cancer, though it expects the drug will also prove effective in breast cancer and other estrogen-related cancers as well. More details.... http://www.chinabiotoday.com/articles/20150917

Antiproliferative agent (IC₅₀ values are 8,13 and 18 μM for K562, CML-CP and CML-BC cells respectively). Inhibits H/R-induced PTK activation. Induces G(2)/M cell cycle arrest and mitochondrial transmembrane potential drop. Modulates MAPK/ERK/JNK and JAK2/STAT3 /AKT signaling. Inhibits PPAR-g. Modulates differentiation. Inhibits cytochrome P450 in vivo. Orally active.

Cardiovascular function improvement, hormone regulation and antitumor activity.
2. The anti-MM activity of Icaritin was mainly mediated by inhibiting IL-6/JAK2/STAT3 signaling.
3. The inhibitory activity of Icariside II on pre-osteoclast RAW264.7 growth was synergized by Icaritin, which maybe contribute to the efficiency of Herba Epimedii extract on curing bone-related diseases, such as osteoporosis.
4. The Icaritin at low concentration (4 or 8 μmol/L) can promote rat chondrocyte proliferation and inhibit cell apoptosis, while the effect of Icaritin on rat chondrocyte at high concentration was reversed.
5. Icaritin might be a new potent inhibitor by inducing S phase arrest and apoptosis in human lung carcinoma A549 cells.
6. Icaritin dose-dependently inhibits ENKL cell proliferation and induces apoptosis and cell cycle arrest at G2/M phase. Additionally, Icaritin upregulates Bax, downregulates Bcl-2 and pBad, and activates caspase-3 and caspase-9.

What is Epimedium ?

Herba epimedii (Epimedium, also called bishop's hat, horny goat weed or yin yang huo), a traditional Chinese medicine, has been widely used as a kidney tonic and antirheumatic medicine for thousands of years. It is a genus of about 60 flowering herbs, cultivated as a ground cover plant and an aphrodisiac. The bioactive components in herba epimedii are mainly prenylated flavonol glycosides, end-products of the flavonoid pathway. Epimedium species are also used as garden plants due to the colorful flowers and leaves. Most of them bloom in the early spring, and the leaves of some species change colors in the fall, while other species retain their leaves year round.

Figure 1 Epimedium

Epimedium Raw Material

The herbs we used to extract icariin is one species of Epimedium, which name is Epimedium brevicornum Maxim. This kind of epimedium only can be abundantly found in Gansu province of China. And because of the growth habit of this kind of herb, which only grows under trees, it can’t to be planted, only can harvest the wild one.

This wild epimedium contains quite a bit of active components, depending on its long growth time and rich nutrient. Usually the content of the icariin is not lower than 1%.

Below photo is the herb specimen which we use. Picking in the epimedium full-bloom stage. And the medicinal value of the herb is the best at this time. The herb we select contains roots, stems, leaves and flowers. And we extract with the whole herb.

 

Figure 2 Epimedium for extract

Epimedium Extract

Epimedium extract is a herbal supplement claimed to be beneficial for the treatment of sexual problems such as impotence. It is believed to contain a number of active components, including plant compounds that may have antioxidant activity and estrogen-like compounds. The major components of Epimedium brevicornum are icariin, epimedium B and epimedium C. It is reported to have anti-inflammatory, anti-proliferative, and anti-tumor effects. It is also reported to have potential effects on the management of erectile dysfunction.

 

Figure 3 HPLC spectrum of icariin

Our specification available is Icariin HPLC 50%- 98%. Below please see the the information for reference:

 

      Figure 4 Epimedium Extract(Icariin)

Derivatives

The plant extracts of epimedium traditionally used for male impotence, and the individual compounds is icariin, were screened against phosphodiesterase-5A1 (PDE5A1) activity. Human recombinant PDE5A1 was used as the enzyme source. The E. brevicornum extract and its active principle icariin were active. To improve its inhibitory activity, some derivatives ware subjected to various structural modifications, which include icaritin, icariside II and 3,7-bis(2-hydroxyethyl) icaritin. There have some scientific papers report that the improved pharmacodynamic profile and lack of cytotoxicity on human fibroblasts make such compounds a promising candidate for further development. We hope that our new products can help you to find more commercial opportunity.

In this way, we can introduce those products as below, and we can also provide more details about the products according to your demand. The 1H-NMR of icaritin and 3,7-bis(2-hydroxyethyl) icaritin is as below.

Product Name	Specification	CAS No.
Icariin	HPLC 50%-98%	489-32-7
icaritin	HPLC 98%	118525-40-9
icariside II	HPLC 98%	113558-15-9
3,7-bis(2-hydroxyethyl) icaritin	HPLC 98%	1067198-74-6

Figure 4 1H-NMR of icaritin and 3,7-bis(2-hydroxyethyl) icaritin

Main Function of Epimedium Extract 

horny goat weed; epimedium; Icariin; penis medicine;epimedium p.e;epimedium brevicornum; shorthorned epimedium herb; Icariins; Icaritin; 3,7-Bis(2-Hydroxyethyl)Icaritin; icariin 60%; icariin 98%; epimedium graepimedium; icarisides II;epimedium sagittatum;epimedium leaf; barrenwort.powder extract

Epimedium has been used to treat male erectile dysfunction in Traditional Chinese Medicine for many centuries. The main functions of Epimedium brevicornum in ancient Chinese books focused on the nourishment of kidney viscera and reinforcement of ‘yang’, resulting in the restoration of erectile function in males.

Epimedium contains chemicals which might help increase blood flow and improve sexual function. It also contains phytoestrogens, chemicals that act somewhat like the female hormone estrogen that might reduce bone loss in postmenopausal women.

Figure 5 some products from epimedium extract

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PAPER

The novel total synthesis of icaritin (1), naturally occurring with important bioactive 8-prenylflavonoid, was performed via a reaction sequence of 8 steps including Baker-Venkataraman reaction, chemoselective benzyl or methoxymethyl protection, dimethyldioxirane (DMDO) oxidation, O-prenylation, Claisen rearrangement and deprotection, starting from 2,4,6-trihydroxyacetophenone and 4-hydroxybenzoic acid in overall yields of 23%. The key step was Claisen rearrangement under microwave irradiation. MS, ¹H and ¹³C NMR techniques have been used to confirm the structures of all synthetic compounds. - See more at: http://www.eurekaselect.com/124334/article

.......

PAPER

Figure 1: Structures of icariin (1), icariside I (2) and icaritin (3).

Synthesis of icariin from kaempferol through regioselective methylation and para-Claisen–Cope rearrangement

Qinggang Mei^1,2, Chun Wang¹, Zhigang Zhao³, Weicheng Yuan² and Guolin Zhang¹

¹Chengdu Institute of Biology, Chinese Academy of Sciences, Chengdu 610041, China
²Chengdu Institute of Organic Chemistry, Chinese Academy of Sciences, Chengdu 610041, China
³College of Chemistry and Environmental Protection Engineering, Southwest University for Nationalities, Chengdu 610041, China...http://www.beilstein-journals.org/bjoc/single/articleFullText.htm?publicId=1860-5397-11-135

http://www.beilstein-journals.org/bjoc/content/supplementary/1860-5397-11-135-S1.pdf

Scheme 1: Reagents and conditions: (a) Ac₂O, pyridine, 94%; (b) BnBr, KI, K₂CO₃, acetone, 85%; (c) Me₂SO₄, K₂CO₃, acetone, MeOH, 82%; (d) MOMCl, N,N-diisopropylethylamine (DIPEA), CH₂Cl₂, 93%; (e) 3,3-dimethylallyl bromide, 18-crown-6, K₂CO₃, acetone, 86%; (f) Eu(fod)₃, NaHCO₃, PhCl, 85 °C, 61%; (g) MeOH, 3 M HCl (aq), reflux, 95%; (h) Pd/C, 1,4-cyclohexadiene, MeOH, 84%.

Scheme 2: Decomposition of 8.

Scheme 3: Claisen rearrangement of flavonol 8.

Scheme 4: Reagents and conditions: (a) 15, DMF/CHCl₃, Ag₂CO₃, molecular sieves (4 Å, powder); (b) 16, CH₂Cl₂, Ag₂O, molecular sieves (4 Å powder), 31% for 2 steps; (c) NH₃ (g), MeOH, 94%; (d) NH₃ (g), MeOH, 63% for 2 steps.

3 Nguyen, V.-S.; Shi, L.; Li, Y.; Wang, Q.-A. Lett. Org. Chem. 2014, 11, 677–681.

4. Dell’Agli, M.; Galli, G. V.; Dal Cero, E.; Belluti, F.; Matera, R.; Zironi, E.; Pagliuca, G.; Bosisio, E. J. Nat. Prod. 2008, 71, 1513–1517.

 1H NMR

13C NMR

HMBC

NOESY

• Liang DL & Zheng SL Effects of icaritin on cytochrome P450 enzymes in rats. Pharmazie 69:301-5 (2014).Read more (PubMed: 24791596) »
• Guo Y  et al. An anticancer agent icaritin induces sustained activation of the extracellular signal-regulated kinase (ERK) pathway and inhibits growth of breast cancer cells. Eur J Pharmacol 658:114-22 (2011). Read more (PubMed: 21376032) »
• Zhu Jf  et al. Icaritin shows potent anti-leukemia activity on chronic myeloid leukemia in vitro and in vivo by regulating MAPK/ERK/JNK and JAK2/STAT3 /AKT signalings. PLoS One 6:e23720 (2011). Read more (PubMed: 21887305) »
• The roots of Epimedium brevicornu Maxim

Patent	Submitted	Granted
Compositions comprising icariside I and anhydroicaritin and methods for making the same [US6399579]		2002-06-04
COSMETIC COMPOSITION CONTAINING HYDROLYSATES OF ICARIIN [US2009170787]	2009-07-02
COMPOUNDS AND METHODS FOR TREATING ESTROGEN RECEPTOR-RELATED DISEASES [US8252835]	2008-06-19	2012-08-28

/////////Beijing Shenogen,  Granted Fast Track Status,  Novel Cancer Drug, Icaritin, New Drug Approval submission,  Beijing Food & Drug Administration, oral traditional Chinese medicine, barrenwort

PHENYL 2-HYDROXYBENZOATE......COCK WILL TEACH YOU NMR

PHENYL 2-HYDROXYBENZOATE, PHENYL SALICYLATE

 COCK WILL TEACH YOU NMR

Formula: C₁₃H₁₀O₃

C₁₃H₁₀O₃
Rule 2, omit O, gives C₁₃H₁₀
13 - 10/2 + 1 = 9 degrees of unsaturation.
Look for 2 aromatic rings plus another pi bond or aliphatic ring.

Show IR answer

The band at 1682 indicates a carbonyl, probably an ester. The band at 3192 indicates C-H aromatic stretch; aromatics also show bands in the regions 1600-1585 and 1500-1400 (C-C in-ring stretch), and 900-675 (C-H out-of-plane). The wide band just to the left of the 3192 band indicates O-H stretch (alcohols and phenols).

This is the structure. See if you can assign the peaks on your own.

 
 
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4-OCTYNE......COCK WILL REACH YOU NMR

 
4-OCTYNE
Formula: C₈H₁₄

 COCK WILL REACH YOU NMR

C₈H₁₄
8 - 14/2 + 1 = 2 degrees of unsaturation.
Look for any 2 of pi bonds or aliphatic rings.

The bands at 3000-2850 indicate C-H alkane stretches. There really aren't many other bands in the spectrum to indicate functional groups. The compound is an alkyne; we would expect to see a carbon-carbon triple bond stretch at 2260-2100, however, this is a weak band at best and often does not show up on IR.

This is the structure. See if you can assign the peaks on your own.

Show NMR answer

The integral values for A, B, and C need to be multiplied by 2 to get a total of 14 protons in the molecule. By convention, integral values on an NMR spectrum are reported as the lowest common multiple.

 
 


 
 


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INTERACTIVE SPECTROSCOPY

SEE



http://www.chem.ucalgary.ca/courses/351/WebContent/spectroscopy/spectroscopy.html

Background:

This organic chemistry learning object allows you to work through a set of spectroscopy problems using an interactive drawing tool. After each attempt, your structure is assessed and you are given feedback to help you work towards the solution. Hints are available in many cases and worked solutions are provided.

The spectrocopy problems:

Each problem contains spectral data (mass spectrum, infra-red, ¹³C NMR and H NMR) for an unknown compound.
You are required to deduce the structure of the unknown compound that is consistent with all the data provided.
Some "general" hints are available to encourage you to look for the right information and to try to get you going. In addition, an online "tutor" will give you feedback on any wrong answers you submit. In general terms, the problems start easy and gradually get harder as you go, but similar or related problems are grouped together to help the learning process.

We are working on adding more problems when time allows....

Last problem update : As of June 18th 2015 there are 56 problems (22 easy, 21 medium, 11 difficult, 2 extreme).

• Use the buttons to show the spectra
• Draw your answer in the window in the left and submit it.
• Review the feedback in the middle column.
• Hints are available after you have made 3 attempts.
  
• A worked solution is available after 8 attempts.
• The score per question is given when you get the answer, it is based on the number of attempts and how many hints you use. When you exit, you will be given your overall total.
  
• The difficulty level is indicated on the downhill skiing scale...



green easy	blue moderate	black difficult	double black extreme

A screen shot is shown below, the drawing area on the left and your answer and feedback on the right
Acknowledgements:

• MS, IR and NMR spectra are adapted from SDBS (National Institute of Advanced Industrial Science and Technology, Japan)
• As of 2015, most of the H-NMR and C-NMR are being converted to simulations created using MestReNova.

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