Description:
Artemisinin content from wikipedia: artesunate (artemisine)traditional Chinese medicine extracted from artemisia annua hadArtemisinin content from wikipedia: artesunate (artemisine)traditional Chinese medicine extracted from artemisia annua had theoxygen of the groups have been half as within the anti-malaria drugethynylation were. Artesunate is China''s first found internationalrecognized natural drugs, on the basis of synthetic derivatives,such as dihydroartemisinin, artemether, artesunate and so on.Artesunate drugs, a low toxicity of strong sex abuse, was approvedas a WTO worldwide in the treatment of malignant malaria malariabrain type and the first choice of drugs.
Introduction: (chemical name 3 R, aS 5, 6 R, aS 8, 9 R, 12 S, 12aR)-eight hydrogen-3, 6, 9-three methyl-3, 12-oxygen bridge-12H-pyranoid and [4, 3-j]-1, 2-benzene and two plug flat-10 (3H)-ketone
Artesunate crystal Chinese alias: artemisia annua had HuangHaoelement, element
English name: Artemisinin
English alias: Arteannuin, Artemisinine, Qinghaosu
CasNo: 63968-64-9
Patent: C15H22O5
Molecular weight: 282.33
Physical properties: colorless needle crystal, taste bitter. Inacetone, acetic acid ethyl ester, chloroform, benzene and glacialacetic acid easily dissolved in ethanol and methanol, ethersoluble, slightly soluble in cold petroleum ether, almost don''tdissolve in water. Melting point of 156-157 °C, the opticalrotations 69 (c = 0.5, CHCl3).
Chemical properties: can be ferrous sulfate reduction, easy tothree benzene phosphorus reaction. Conventional state more stable,but it soon in alkali solution, it''s happening at the same timeopen ester ring rearrangement and decomposition.
Function and purpose: pharmacology study shows that artesunateplasmodium falciparum within a period of red exterminate actiondirectly, to the organization period is invalid, of theexperimental animal is very low in the body in absorption fast,wide distribution, drain faster. Mainly used for JianRi anopheles,malignant anopheles symptoms under control, and resistance tochloroquine insect strains of the treatment, can also be used as atreatment for type unleashed vicious anopheles, such as brain type,icteric model, etc. Can be used to treat systemic lupuserythematosus (sle) and the disk lupus erythematosus.
Study history in 1969 China began to antimalarial medicineresearch. After more than 380 times the rat anopheles screening, inOctober 1971, traditional Chinese medicine has artesunate screeningof success. 1972 from Chinese traditional medicine have beenisolated artesunate anti-malaria effective monomer, namedartemisinin, to rat anopheles, monkey anopheles inhibition rate tothe 100% human.
In 1973, the clinical research has achieved and laboratoryconsistent results, antimalarial drug artesunate was born.
In October 1981 at a conference in Beijing, the world healthorganization of the "artesunate" international conference, China''sthe artemisinin chemical research "the speech, cause the delegatesof great interest, and believe that" this new discovery moreimportant significance for further design is in new drug synthesisdirection ".
In 1986, to get the new kind of new drug artesunate certificate,dihydroartemisinin also obtained a certificate of new drugs. Theseresults were obtained the country and national invention 10 greatscientific and technological achievement award.
On September 23, 2011, the researchers YouYou artesunateslaughter for the New York lasker award, this is the first time aChinese scientists for this international medical award.
November 15, 2011, China''s traditional Chinese medicine academyof sciences is held in Beijing "2011 science and technology workcongress". Meeting the carcasses of traditional Chinese medicineacademy of sciences awarded YouYou China outstanding contributionaward, awards artesunate research team is 1 million yuan RMB.
The main source of artesunate source is mainly from artemisiaannua had extracted directly get; Or extraction of artemisia annuahad high levels of conventional acid, and then get halfsynthesis.
Now in addition to artemisia annua had artemisia annua hadoutside, has not been found to contain artesunate natural plantresources of the other. Artemisia annua had although is the world svariety, but the conventional view with different producing areascontaining vary enormously. According to the results of the study,so far, in addition to chongqing, China Eastern, fujian, guangxi,hainan the parts, most of the world of artemisia annua had producedin areas of artemisinin content are very low, no use value.According to the relevant state department investigation in theglobal scope, at present, only China chongqing Yang stepped in thegrowth of wu agree mountains artesunate just have industrialrefining value. For this particular drug resources, the nationalrelated ministries from 80 s clearly stipulates the original plantof artesunate (only), seeds, dry fresh grass and all artesunateapis will be prohibited from exports.
Extraction process extracted from artemisia artesunate methodbased on the principle of extraction based, basically have etherleaching solvent naphtha leaching formulation and formulation. Theessential oil was mainly by steam distillation extraction, vacuumdistillation separation, the process for: feed-addingwater-distilling-cooling-water-oil separation-essential oil;Non-volatile components in the main USES organic solventextraction, column chromatography and heavy crystallizationseparation, basic process for: dry-broken-soak, extraction(repeatedly)-concentrated extract-crude products-refined.
Synthesis methods
Half a synthetic route
Conventional acid as raw material from the start, after fivestep reaction get artemisinin, must rate is about 35 to 50%.
The first step: conventional acid in heavy nitrogenmethane/iodine methane/acid catalytic reaction with methanol, againin nickel chloride existence condition, be selective reductionsodium borohydride under two hydrogen fengxian acid methylester;
The second step: two hydrogen fengxian acid methyl ester in THFor ethyl ether solution with aluminum reduction between lithiumhydrogenated into alcohol;
Step 3: only alcohol in methanol/methylenechloride/chloroform/carbon tetrachloride solution by ozoneoxidation get peroxide, dry in again after using xylene p-toluenesulfonic acid treatment get ring ene ether;
Step 4: circular ene ether dissolved in solvent, inphotosensitizer rosy/methylene blue/bamboo red meat are bacteriaunder light oxidation connate into two oxygen sihuan intermediates,garnish with acid treatment get decarboxylation artesunate;
Step 5: decarboxylation artesunate in four oxidation rutheniumoxidation system or chromium acid oxidizer under the function ofoxidation get artesunate.
The synthetic route: but by a variety of route for the synthesisof artesunate. If Schmil reported in 1983, a key propylene alcoholethers application compounds in the light of the low temperatureoxidation reaction bringing in oxygen radicals of all syntheticroute, reaction to ()-2-different mint alcohol as raw materials,keep in the material the six-member ring, ring three side chainalkylation, form intermediates, finally ring synthesis includingcrosses oxygen bridge and a half times the broad lactone.XuXingXiang equal to 1986 reported artesunate
