PL212523B1 - Method for manufacture of 4'-hydroxyflavone - Google Patents
Method for manufacture of 4'-hydroxyflavoneInfo
- Publication number
- PL212523B1 PL212523B1 PL373686A PL37368605A PL212523B1 PL 212523 B1 PL212523 B1 PL 212523B1 PL 373686 A PL373686 A PL 373686A PL 37368605 A PL37368605 A PL 37368605A PL 212523 B1 PL212523 B1 PL 212523B1
- Authority
- PL
- Poland
- Prior art keywords
- flavone
- carried out
- hydroxylation
- hydroxyflavone
- manufacture
- Prior art date
Links
- SHGLJXBLXNNCTE-UHFFFAOYSA-N 2-(4-hydroxyphenyl)chromen-4-one Chemical compound C1=CC(O)=CC=C1C1=CC(=O)C2=CC=CC=C2O1 SHGLJXBLXNNCTE-UHFFFAOYSA-N 0.000 title claims description 16
- 238000000034 method Methods 0.000 title claims description 12
- 238000004519 manufacturing process Methods 0.000 title claims description 3
- 238000005805 hydroxylation reaction Methods 0.000 claims description 6
- GAMYVSCDDLXAQW-AOIWZFSPSA-N Thermopsosid Natural products O(C)c1c(O)ccc(C=2Oc3c(c(O)cc(O[C@H]4[C@H](O)[C@@H](O)[C@H](O)[C@H](CO)O4)c3)C(=O)C=2)c1 GAMYVSCDDLXAQW-AOIWZFSPSA-N 0.000 claims description 5
- 229930003944 flavone Natural products 0.000 claims description 5
- 150000002212 flavone derivatives Chemical class 0.000 claims description 5
- 235000011949 flavones Nutrition 0.000 claims description 5
- VHBFFQKBGNRLFZ-UHFFFAOYSA-N vitamin p Natural products O1C2=CC=CC=C2C(=O)C=C1C1=CC=CC=C1 VHBFFQKBGNRLFZ-UHFFFAOYSA-N 0.000 claims description 5
- 241000909534 Penicillium chermesinum Species 0.000 claims description 4
- 230000033444 hydroxylation Effects 0.000 claims description 4
- 230000008569 process Effects 0.000 claims description 4
- 102000004190 Enzymes Human genes 0.000 claims description 3
- 108090000790 Enzymes Proteins 0.000 claims description 3
- 230000009466 transformation Effects 0.000 claims description 3
- 230000000813 microbial effect Effects 0.000 claims description 2
- 239000000758 substrate Substances 0.000 claims 2
- 238000003756 stirring Methods 0.000 claims 1
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 6
- 239000000047 product Substances 0.000 description 4
- 150000001875 compounds Chemical class 0.000 description 3
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 2
- 230000003078 antioxidant effect Effects 0.000 description 2
- 150000002632 lipids Chemical class 0.000 description 2
- 238000002360 preparation method Methods 0.000 description 2
- 241000235389 Absidia Species 0.000 description 1
- 241000233866 Fungi Species 0.000 description 1
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 230000003217 anti-cancerogenic effect Effects 0.000 description 1
- 230000002790 anti-mutagenic effect Effects 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- 210000004027 cell Anatomy 0.000 description 1
- 210000000170 cell membrane Anatomy 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 239000007795 chemical reaction product Substances 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- 239000012043 crude product Substances 0.000 description 1
- WBKFWQBXFREOFH-UHFFFAOYSA-N dichloromethane;ethyl acetate Chemical compound ClCCl.CCOC(C)=O WBKFWQBXFREOFH-UHFFFAOYSA-N 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 239000003480 eluent Substances 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 229930003935 flavonoid Natural products 0.000 description 1
- 150000002215 flavonoids Chemical class 0.000 description 1
- 235000017173 flavonoids Nutrition 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 230000009931 harmful effect Effects 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- 244000005700 microbiome Species 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- 230000003472 neutralizing effect Effects 0.000 description 1
- 235000016709 nutrition Nutrition 0.000 description 1
- 230000035764 nutrition Effects 0.000 description 1
- 230000036542 oxidative stress Effects 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- 239000000376 reactant Substances 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 230000003595 spectral effect Effects 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
Landscapes
- Preparation Of Compounds By Using Micro-Organisms (AREA)
Description
Przedmiotem wynalazku jest sposób wytwarzania 4'-hydroksyflawonu, o wzorze 2 przedstawionym na rysunku.The present invention relates to a process for the preparation of a 4'-hydroxy flavone of formula II as shown in the drawing.
Związek ten może znaleźć zastosowanie w produkcji preparatów farmaceutycznych, np. niektórych leków o działaniu antymutagennym/antykancerogennym.This compound may find application in the production of pharmaceutical preparations, e.g. some drugs with antimutagenic / anti-carcinogenic activity.
Rosnące zapotrzebowanie przemysłu farmaceutycznego na związki chroniące organizm ludzki przed szkodliwymi skutkami stresu oksydacyjnego skłania do poszukiwania związków o podwyższonych właściwościach antyoksydacyjnych. Hydroksylacja pierścienia B flawonoidów ma istotny wpływ na zwiększenie ich właściwości przeciwutleniających.The growing demand of the pharmaceutical industry for compounds that protect the human body against the harmful effects of oxidative stress prompts the search for compounds with enhanced antioxidant properties. The B-ring hydroxylation of flavonoids has a significant effect on increasing their antioxidant properties.
Nie jest znane otrzymanie 4'-hydroksyflawonu przy użyciu metod chemicznych.It is not known to obtain 4'-hydroxy flavone by chemical methods.
Znany jest sposób otrzymywania 4'-hydroksyflawonu na drodze mikrobiologicznej hydroksylacji pozycji C-4' flawonu za pomocą Absidia blackesleeana (NRRL 1306). W metodzie tej obserwuje się niską (25%) wydajność pożądanego produktu (Abdel-Rahim S. Ibrahim, Yusuf J. Abul-Hajj; Xenobiotica, 1990, vol. 20, no. 4, ss. 363-373).There is a known method of obtaining 4'-hydroxy flavone by microbial hydroxylation of the C-4 'position of the flavone with Absidia blackesleeana (NRRL 1306). This method shows a low (25%) yield of the desired product (Abdel-Rahim S. Ibrahim, Yusuf J. Abul-Hajj; Xenobiotica, 1990, vol. 20, no. 4, pp. 363-373).
Istota wynalazku polega na tym, że reakcję hydroksylacji pozycji C-4' flawonu, o wzorze 1, prowadzi się za pomocą systemu enzymatycznego kultury szczepu grzyba z gatunku Penicillium chermesinum.The essence of the invention consists in the fact that the hydroxylation reaction of the C-4 'position of the flavone of the formula 1 is carried out with the enzyme system of the culture of a fungus strain of the genus Penicillium chermesinum.
Korzystne jest, gdy reakcja prowadzona jest wodną kulturą szczepu, przy ciągłym mieszaniu reagentów, w temperaturze 288-308 K.It is advantageous if the reaction is carried out in an aqueous culture of the strain, with continuous mixing of the reactants, at a temperature of 288-308 K.
Postępując zgodnie z wynalazkiem, w wyniku działania układu enzymatycznego zawartego w komórkach grzyba Penicillium chermesinum, następuje reakcja hydroksylacji pozycji C-4' flawonu. Uzyskany w ten sposób produkt wydziela się z wodnej kultury mikroorganizmu, znanym sposobem przez ekstrakcję octanem etylu.By following the invention, as a result of the action of the enzyme system contained in the cells of the fungus Penicillium chermesinum, a hydroxylation reaction takes place at the C-4 'position of the flavone. The product thus obtained is separated from the aqueous culture of the microorganism by extraction with ethyl acetate in a known manner.
Będący przedmiotem wynalazku 4'-hydroksyflawon, o wzorze 1, lokalizując się na powierzchni membran lipidowych, na granicy faz jest zdolny do neutralizowania rodników, nie dopuszczając do ich ataku na lipidy decydujące o prawidłowej strukturze i funkcji błon komórkowych (J. Terao, Μ. K. Piskula; Nutrition, 1999, vol. 15, 790).The 4'-hydroxy flavone of the formula 1, being the subject of the invention, by locating on the surface of lipid membranes, at the phase boundary, is capable of neutralizing radicals, preventing them from attacking the lipids that determine the proper structure and function of cell membranes (J. Terao, Μ. K. Piskula; Nutrition, 1999, vol. 15, 790).
Zasadniczą zaletą wynalazku jest otrzymanie 4'-hydroksyflawonu, o wzorze 2, jako jedynego produktu reakcji z wydajnością 95%, w temperaturze pokojowej i pH bliskim obojętnego.The main advantage of the invention is the preparation of the 4'-hydroxy flavone of formula 2 as the sole reaction product with a yield of 95%, at room temperature and near neutral pH.
Wynalazek jest bliżej objaśniony na przykładzie wykonania.The invention is explained in more detail using an exemplary embodiment.
P r z y k ł a dP r z k ł a d
Do kolby Erlenmajera o pojemności 250 cm3, w której znajduje się 100 cm3 sterylnej pożywki zawierającej 3 g glukozy i 1 g aminobaku zaszczepia się Penicillium chermesinum. Po dwóch dniach wzrostu dodaje się 10 mg flawonu, o wzorze 1, rozpuszczonego w 0,5 cm3 acetonu. Transformację prowadzi się przy ciągłym wstrząsaniu przez 20 dni. Następnie uzyskany roztwór transformacyjny ekstrahuje się trzykrotnie octanem etylu, osusza bezwodnym siarczanem magnezu i odparowuje rozpuszczalnik. Otrzymuje się 19 mg surowego produktu, który oczyszcza się chromatograficznie używając jako eluentu mieszaniny chlorek metylenu-octan etylu, w stosunku 1:1.To the Erlenmeyer flask with a capacity of 250 cm 3, which is 100 cm 3 of sterile medium containing 3 g of glucose and 1 g aminobaku inoculated with Penicillium chermesinum. After two days of growth, 10 mg of flavone 1, dissolved in 0.5 cm 3 of acetone, are added. The transformation is carried out under continuous shaking for 20 days. Then the resulting transformation solution was extracted three times with ethyl acetate, dried with anhydrous magnesium sulfate and the solvent was evaporated. 19 mg of crude product are obtained, which product is purified by chromatography using a 1: 1 mixture of methylene chloride-ethyl acetate as eluent.
Na tej drodze otrzymuje się 9,5 mg 4'-hydroksyflawonu (wydajność 95%), o wzorze 2.In this way 9.5 mg of 4'-hydroxy flavone (95% yield) of the formula 2 are obtained.
Uzyskany produkt charakteryzuje się następującymi danymi spektralnymi:The obtained product is characterized by the following spectral data:
1H NMR (CD3OD) δ (ppm), 1 H NMR (CD 3 OD) δ (ppm)
6,78 (s, 1H, H-3); 6,94 (d, 2H, J = 8,84 Hz, H-3', H-5'), 7,46 (t, 1H, H-6);6.78 (s, 1H, H-3); 6.94 (d, 2H, J = 8.84Hz, H-3 ', H-5'), 7.46 (t, 1H, H-6);
7,69 (d, 1H, J = 8,35 Hz, H-8); 7,78 (t, 1H, H-7);7.69 (d, 1H, J = 8.35Hz, H-8); 7.78 (t, 1H, H-7);
7,91 (d, 2H, J = 8,83 Hz, H-2', H-6'); 8,12 (d, 2H, J = 7,91 Hz, H-5).7.91 (d, 2H, J = 8.83Hz, H-2 ', H-6'); 8.12 (d, 2H, J = 7.91Hz, H-5).
Claims (3)
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| PL373686A PL212523B1 (en) | 2005-03-15 | 2005-03-15 | Method for manufacture of 4'-hydroxyflavone |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| PL373686A PL212523B1 (en) | 2005-03-15 | 2005-03-15 | Method for manufacture of 4'-hydroxyflavone |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| PL373686A1 PL373686A1 (en) | 2005-09-05 |
| PL212523B1 true PL212523B1 (en) | 2012-10-31 |
Family
ID=36241800
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| PL373686A PL212523B1 (en) | 2005-03-15 | 2005-03-15 | Method for manufacture of 4'-hydroxyflavone |
Country Status (1)
| Country | Link |
|---|---|
| PL (1) | PL212523B1 (en) |
-
2005
- 2005-03-15 PL PL373686A patent/PL212523B1/en not_active IP Right Cessation
Also Published As
| Publication number | Publication date |
|---|---|
| PL373686A1 (en) | 2005-09-05 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| KR20150055471A (en) | Novel compound, a preparing method thereof, and a use thereof as inhibitors of histone demethylase | |
| Pan et al. | Cladosins LO, new hybrid polyketides from the endophytic fungus Cladosporium sphaerospermum WBS017 | |
| CN109689877B (en) | Method for producing large amount of grape essence from cell culture of grape vine tissue by using stevioside | |
| US20180057524A1 (en) | Compounds from invasive salvinias and methods of using the same | |
| Kato et al. | In vitro and ex vivo free radical scavenging activities of carazostatin, carbazomycin B and their derivatives. | |
| US5021406A (en) | 2-pyranone derivative and process for production thereof | |
| EP0329361B1 (en) | 2-pyranone derivatives and process for production thereof | |
| ES2318053T3 (en) | ANTIHELMINTICA SUBSTANCE FKI-1033 AND PROCEDURE FOR THE PRODUCTION OF THE SAME. | |
| JP2011211921A (en) | Method for producing cyclic phosphatidic acid | |
| PL212522B1 (en) | Method for manufacture of 4',5,7-trihydroxyflavone | |
| EP2468879B1 (en) | A-87774 compound or salt thereof, method for producing the compound or salt thereof, and agrochemical containing the compound or salt thereof as active ingredient | |
| WO2007105280A9 (en) | Process for production of acylated derivative of epigallocatechin gallate | |
| JPH0613542B2 (en) | New compound No. 51262 substance, its production method, and herbicide and plant regulator containing it as an active ingredient | |
| PL212959B1 (en) | Method for the manufacture of 7,4'-dihydroxy flavone | |
| KR100646829B1 (en) | New adenosine derivatives and salts thereof, methods for their preparation, pharmaceutical compositions for antibiotics thereof, and their use as biological pesticides | |
| PL212521B1 (en) | Method for manufacture of 7-hydroxyflavone | |
| CN120574203A (en) | A curcumin analogue with a benzopyran structure, and its preparation method and application | |
| PL247265B1 (en) | Method for producing 4',5-dihydroxy-7-O-β-D-(4''-O-methylglucopyranosyl)-isoflavone | |
| Kato et al. | IV VITRO AND EX VIVO FREE RADICAL SCAVENGING ACTIVITIES OF CARAZOSTATIN, CARBAZOMYCIN B AND THEIR DERIVATIVES | |
| PL246798B1 (en) | Method for producing 2-methyl-4-O-β-D-(4'-O-methylglucopyranosyl)-benzoic acid | |
| KR100919368B1 (en) | Human platelet aggregation and preparation method of inhibitor of soybean lipoxygenase | |
| PL212960B1 (en) | Production method of 7,4'-dihydroxyflavanon | |
| PL212520B1 (en) | Method for manufacture of 3-hydroxyflavone | |
| EP3597647A1 (en) | Novel pochoniolide compound and use thereof | |
| PL212833B1 (en) | Method for the manufacture of 5,7-dihydroxy-6,4'-dimethoxy flavone |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| LICE | Declarations of willingness to grant licence |
Effective date: 20120625 |
|
| LAPS | Decisions on the lapse of the protection rights |
Effective date: 20080315 |