PL212520B1 - Method for manufacture of 3-hydroxyflavone - Google Patents
Method for manufacture of 3-hydroxyflavoneInfo
- Publication number
- PL212520B1 PL212520B1 PL373685A PL37368505A PL212520B1 PL 212520 B1 PL212520 B1 PL 212520B1 PL 373685 A PL373685 A PL 373685A PL 37368505 A PL37368505 A PL 37368505A PL 212520 B1 PL212520 B1 PL 212520B1
- Authority
- PL
- Poland
- Prior art keywords
- carried out
- substrate
- hydroxyflavone
- manufacture
- hydroxylation
- Prior art date
Links
- HVQAJTFOCKOKIN-UHFFFAOYSA-N flavonol Chemical compound O1C2=CC=CC=C2C(=O)C(O)=C1C1=CC=CC=C1 HVQAJTFOCKOKIN-UHFFFAOYSA-N 0.000 title claims description 16
- 238000000034 method Methods 0.000 title claims description 13
- 238000004519 manufacturing process Methods 0.000 title claims 2
- 241000909534 Penicillium chermesinum Species 0.000 claims description 4
- 125000004432 carbon atom Chemical group C* 0.000 claims description 4
- 230000033444 hydroxylation Effects 0.000 claims description 4
- 238000005805 hydroxylation reaction Methods 0.000 claims description 4
- ZONYXWQDUYMKFB-UHFFFAOYSA-N SJ000286395 Natural products O1C2=CC=CC=C2C(=O)CC1C1=CC=CC=C1 ZONYXWQDUYMKFB-UHFFFAOYSA-N 0.000 claims description 3
- 229930003949 flavanone Natural products 0.000 claims description 3
- 150000002207 flavanone derivatives Chemical class 0.000 claims description 3
- 235000011981 flavanones Nutrition 0.000 claims description 3
- 239000000758 substrate Substances 0.000 claims description 3
- 230000009466 transformation Effects 0.000 claims description 3
- 229910052799 carbon Inorganic materials 0.000 claims description 2
- 230000002255 enzymatic effect Effects 0.000 claims description 2
- 241000233866 Fungi Species 0.000 claims 1
- 230000000813 microbial effect Effects 0.000 claims 1
- 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 3
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 2
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 2
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 2
- 238000006356 dehydrogenation reaction Methods 0.000 description 2
- 229910021645 metal ion Inorganic materials 0.000 description 2
- 238000002360 preparation method Methods 0.000 description 2
- 241000228245 Aspergillus niger Species 0.000 description 1
- 201000001320 Atherosclerosis Diseases 0.000 description 1
- 208000024172 Cardiovascular disease Diseases 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- -1 Flavonoid Compounds Chemical class 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
- 239000003963 antioxidant agent Substances 0.000 description 1
- 235000006708 antioxidants Nutrition 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 230000001413 cellular effect Effects 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
- 150000001875 compounds Chemical class 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
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 229940079593 drug Drugs 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
- 235000017173 flavonoids Nutrition 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 229910052742 iron Inorganic materials 0.000 description 1
- 230000002906 microbiologic effect Effects 0.000 description 1
- 244000005700 microbiome Species 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 229930014626 natural product Natural products 0.000 description 1
- 230000001613 neoplastic effect Effects 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- 230000004792 oxidative damage Effects 0.000 description 1
- 230000008506 pathogenesis Effects 0.000 description 1
- 231100000915 pathological change Toxicity 0.000 description 1
- 230000036285 pathological change Effects 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 3-hydroksyflawonu, o wzorze 2 przedstawionym na rysunku.The present invention relates to a process for the preparation of a 3-hydroxy flavone of formula 2 shown in the drawing.
Związek ten może znaleźć zastosowanie jako składnik niektórych leków, np. zmniejszających ilość uszkodzeń oksydacyjnych na poziomie komórki.This compound may find use as a component of some drugs, e.g. to reduce the amount of oxidative damage at the cellular level.
Udowodnienie udziału wolnych rodników w patogenezie wielu chorób układu krążenia np. miażdżycy oraz chorób nowotworowych stwarza konieczność poszukiwania przeciwutleniaczy jako potencjalnych czynników ochrony przed tego typu zmianami patologicznymi.Proving the participation of free radicals in the pathogenesis of many cardiovascular diseases, e.g. atherosclerosis and neoplastic diseases, it is necessary to look for antioxidants as potential protection factors against this type of pathological changes.
Znane są sposoby otrzymywania 3-hydroksyflawonu przy użyciu metod chemicznych (Ib Thomsen and Kurt B. G. Torssell, Acta Chemica Scandinavica, Section B, 1988,vol. 42, ss. 303-308), (T. A. Geissman, The Chemistry of Flavonoid Compounds, Ed. Pergamon, London; Macmillan, New York, 1962, s. 156).There are known methods of obtaining 3-hydroxy flavone using chemical methods (Ib Thomsen and Kurt BG Torssell, Acta Chemica Scandinavica, Section B, 1988, vol. 42, pp. 303-308), (TA Geissman, The Chemistry of Flavonoid Compounds, Ed Pergamon, London; Macmillan, New York, 1962, p. 156).
Znany jest też sposób otrzymywania 3-hydroksyflawonu na drodze mikrobiologicznej, jednoczesnej dehydrogenacji przy 2 i 3 atomie węgla i hydroksylacji pozycji C-3 flawanonu za pomocą Aspergillus niger NRRL 599. W metodzie tej obserwuje się bardzo niską wydajność (około 6%) pożądanego produktu (Abdel-Rahim Ibrahim, Yusuf J. Abul-Hajj, Journal of Natural Products, 1990, vol. 53 (3), ss. 644-656).There is also a known method of obtaining 3-hydroxy flavone by microbiological simultaneous dehydrogenation at 2 and 3 carbon atoms and hydroxylation of the C-3 position of the flavanone with Aspergillus niger NRRL 599. In this method, a very low yield (about 6%) of the desired product is observed ( Abdel-Rahim Ibrahim, Yusuf J. Abul-Hajj, Journal of Natural Products, 1990, vol. 53 (3), pp. 644-656).
Istota wynalazku polega na tym, że substrat poddaje się dehydrogenacji przy 2 i 3 atomie węgla połączonej z hydroksylacją pozycji C-3 przy pomocy systemu enzymatycznego szczepu grzyba z gatunku Penicillium chermesinum.The essence of the invention consists in the fact that the substrate is dehydrogenated at 2 and 3 carbon atoms combined with hydroxylation of the C-3 position by means of the enzymatic system of the Penicillium chermesinum species.
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, nastę puje reakcja jednoczesnej dehydrogenacji przy 2 i 3 atomie w ę gla i hydroksylacji pozycji C-3. Uzyskany w ten sposób produkt wydziela si ę z wodnej kultury mikroorganizmu, znanym sposobem przez ekstrakcję octanem etylu.Following the invention, as a result of the action of the enzyme system contained in the cells of the fungus Penicillium chermesinum, there is a simultaneous dehydrogenation reaction at the 2nd and 3rd carbon atom and the hydroxylation of the C-3 position. 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 3-hydroksyflawon, dzięki obecności ugrupowań 3-hydroksy i 4-keto, jest zdolny do chelatowania jonów metali, np. ż elaza, przez co ograniczona staje się zdolność jonów metali do katalizowania tworzenia wolnych rodników (Pier-Giorgio Pietta; J. Nat. Prod., 2000, vol. 63, ss. 1035-1042).The inventive 3-hydroxy flavone, due to the presence of 3-hydroxy and 4-keto groups, is capable of chelating metal ions, e.g. iron, thus reducing the ability of metal ions to catalyze the formation of free radicals (Pier-Giorgio Pietta; J Nat. Prod., 2000, vol. 63, pp. 1035-1042).
Zasadniczą zaletą wynalazku jest otrzymanie 3-hydroksyflawonu jako jedynego produktu reakcji z wydajnością 91%, w temperaturze pokojowej i pH bliskim oboj ętnego.The main advantage of the invention is the preparation of 3-hydroxy flavone as the sole reaction product with a yield of 91%, at room temperature and near neutral pH.
Wynalazek jest bliżej objaśniony w przykładzie wykonania.The invention is explained in more detail in an embodiment.
P r z y k ł a d. Do kolby Erlenmajera o pojemno ś ci 250 cm3, w której znajduje się 100 cm3 sterylnej pożywki zawierającej 3 g glukozy i 1 g aminobaku wprowadza się Penicillium chermesinum. Po dwóch dniach wzrostu kultury, w temperaturze 293 K, dodaje się 10 mg flawanonu, o wzorze 1, rozpuszczonego w 0,5 cm3 acetonu. Transformację prowadzi się przy ciągłym wstrząsaniu przez 13 dni. Następnie uzyskany roztwór transformacyjny ekstrahuje się trzykrotnie octanem etylu, osusza bezwodnym siarczanem magnezu i odparowuje rozpuszczalnik.Example d. To the Erlenmeyer flask with a capacity of 250 cm COG 3, in which the 100 cm 3 of sterile medium containing 3 g of glucose and 1 g aminobaku introduced into Penicillium chermesinum. After two days of growth of the culture, at the temperature of 293 K, 10 mg of flavanone of the formula I dissolved in 0.5 cm 3 of acetone are added. The transformation is carried out under continuous shaking for 13 days. Then the resulting transformation solution was extracted three times with ethyl acetate, dried with anhydrous magnesium sulfate and the solvent was evaporated.
Otrzymuje się 16 mg surowego produktu, który oczyszcza się chromatograficznie używając jako eluentu mieszaniny chlorek metylenu-octan etylu, w stosunku 1:1. Na tej drodze otrzymuje się 9,1 mg 3-hydroksyflawonu (wydajność 91%).16 mg of crude product are obtained which are purified by chromatography using a 1: 1 mixture of methylene chloride-ethyl acetate as eluent. In this way, 9.1 mg of 3-hydroxy flavone are obtained (91% yield).
Uzyskany produkt charakteryzuje się następującymi danymi spektralnymi:The obtained product is characterized by the following spectral data:
1H NMR (CDCl3) δ (ppm) 7,02 (s, 1H, 3-OH); 1 H NMR (CDCl3) δ (ppm) 7.02 (s, 1H, 3-OH);
7,47 (m, 5H, H-6, H-8, H-3', H-4' H-5');7.47 (m, 5H, H-6, H-8, H-3 ', H-4' H-5 ');
7,64 (t, 1H, H-7); 8,24 (d, 3H, J = 9,84 Hz, H-5, H-2' H-6').7.64 (t, 1H, H-7); 8.24 (d, 3H, J = 9.84Hz, H-5, H-2 'H-6').
Claims (3)
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| PL373685A PL212520B1 (en) | 2005-03-15 | 2005-03-15 | Method for manufacture of 3-hydroxyflavone |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| PL373685A PL212520B1 (en) | 2005-03-15 | 2005-03-15 | Method for manufacture of 3-hydroxyflavone |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| PL373685A1 PL373685A1 (en) | 2005-09-05 |
| PL212520B1 true PL212520B1 (en) | 2012-10-31 |
Family
ID=36241799
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| PL373685A PL212520B1 (en) | 2005-03-15 | 2005-03-15 | Method for manufacture of 3-hydroxyflavone |
Country Status (1)
| Country | Link |
|---|---|
| PL (1) | PL212520B1 (en) |
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2005
- 2005-03-15 PL PL373685A patent/PL212520B1/en not_active IP Right Cessation
Also Published As
| Publication number | Publication date |
|---|---|
| PL373685A1 (en) | 2005-09-05 |
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