PL203020B1 - Method for obtaining ethyl (3-metoxyphenyl)-1-(-)-S acetate and ethyl (3-bromophenyl)-1-(-)S acetate by biotransformation - Google Patents
Method for obtaining ethyl (3-metoxyphenyl)-1-(-)-S acetate and ethyl (3-bromophenyl)-1-(-)S acetate by biotransformationInfo
- Publication number
- PL203020B1 PL203020B1 PL368393A PL36839304A PL203020B1 PL 203020 B1 PL203020 B1 PL 203020B1 PL 368393 A PL368393 A PL 368393A PL 36839304 A PL36839304 A PL 36839304A PL 203020 B1 PL203020 B1 PL 203020B1
- Authority
- PL
- Poland
- Prior art keywords
- acetate
- bromophenyl
- ethyl acetate
- ethyl
- biotransformation
- Prior art date
Links
- 238000000034 method Methods 0.000 title claims description 12
- 230000036983 biotransformation Effects 0.000 title claims description 8
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 title description 5
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 title 2
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Natural products CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 32
- 239000000758 substrate Substances 0.000 claims description 9
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims description 8
- 241000196324 Embryophyta Species 0.000 claims description 8
- -1 (±) -1- (3-bromophenyl) ethyl Chemical group 0.000 claims description 6
- 230000007062 hydrolysis Effects 0.000 claims description 6
- 238000006460 hydrolysis reaction Methods 0.000 claims description 6
- 244000000626 Daucus carota Species 0.000 claims description 4
- 235000002767 Daucus carota Nutrition 0.000 claims description 4
- 239000008363 phosphate buffer Substances 0.000 claims description 4
- 239000000725 suspension Substances 0.000 claims description 4
- 235000013311 vegetables Nutrition 0.000 claims description 4
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 8
- 238000004817 gas chromatography Methods 0.000 description 6
- 150000001242 acetic acid derivatives Chemical class 0.000 description 4
- 150000001298 alcohols Chemical class 0.000 description 4
- 230000009466 transformation Effects 0.000 description 4
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 3
- 244000141359 Malus pumila Species 0.000 description 3
- 238000004440 column chromatography Methods 0.000 description 3
- 150000001875 compounds Chemical class 0.000 description 3
- 239000000203 mixture Substances 0.000 description 3
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 2
- 235000011430 Malus pumila Nutrition 0.000 description 2
- 235000015103 Malus silvestris Nutrition 0.000 description 2
- 244000061456 Solanum tuberosum Species 0.000 description 2
- 235000002595 Solanum tuberosum Nutrition 0.000 description 2
- 239000007853 buffer solution Substances 0.000 description 2
- 239000012159 carrier gas Substances 0.000 description 2
- 150000002148 esters Chemical class 0.000 description 2
- 239000001257 hydrogen Substances 0.000 description 2
- 229910052739 hydrogen Inorganic materials 0.000 description 2
- 238000000711 polarimetry Methods 0.000 description 2
- 238000010183 spectrum analysis Methods 0.000 description 2
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- 240000008892 Helianthus tuberosus Species 0.000 description 1
- 235000021016 apples Nutrition 0.000 description 1
- 239000011942 biocatalyst Substances 0.000 description 1
- 239000006285 cell suspension Substances 0.000 description 1
- 230000002255 enzymatic effect Effects 0.000 description 1
- 150000002576 ketones Chemical class 0.000 description 1
- 150000002894 organic compounds Chemical class 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 150000002989 phenols Chemical class 0.000 description 1
- 239000012451 post-reaction mixture Substances 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 238000007127 saponification reaction Methods 0.000 description 1
- JXOHGGNKMLTUBP-HSUXUTPPSA-N shikimic acid Chemical compound O[C@@H]1CC(C(O)=O)=C[C@@H](O)[C@H]1O JXOHGGNKMLTUBP-HSUXUTPPSA-N 0.000 description 1
- JXOHGGNKMLTUBP-JKUQZMGJSA-N shikimic acid Natural products O[C@@H]1CC(C(O)=O)=C[C@H](O)[C@@H]1O JXOHGGNKMLTUBP-JKUQZMGJSA-N 0.000 description 1
- 150000003364 shikimic acids Chemical class 0.000 description 1
- 230000000707 stereoselective effect Effects 0.000 description 1
- 150000003429 steroid acids Chemical class 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 150000003505 terpenes Chemical class 0.000 description 1
- 235000007586 terpenes Nutrition 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P20/00—Technologies relating to chemical industry
- Y02P20/50—Improvements relating to the production of bulk chemicals
- Y02P20/52—Improvements relating to the production of bulk chemicals using catalysts, e.g. selective catalysts
Landscapes
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Description
Opis wynalazkuDescription of the invention
Przedmiotem wynalazku jest sposób otrzymywania octanu S-(-)-1-(3-metoksyfenylo)etylu i octanu S-(- )-1-(3-bromofenylo)etylu drogą biotransformacji.The present invention relates to a process for the preparation of S - (-) - 1- (3-methoxyphenyl) ethyl acetate and S - (-) -1- (3-bromophenyl) ethyl acetate by biotransformation.
Związki te mogą znaleźć zastosowanie w prowadzeniu stereospecyficznych syntez związków organicznych.These compounds may find use in the conduct of stereospecific syntheses of organic compounds.
Powszechnie znanych jest wiele metod hydrolizy octanów na drodze chemicznej. Znana jest również ich hydroliza na drodze biotransformacji przy użyciu roślin wyższych. (A. Mironowicz, K. Kromer, P. Pawłowicz, A. Siewiński, „Abilities of some higher planst to hydrolyze the acetates of phenols and aromatic-aliphatic alcohols”, Acta Soc. Bot. Polon., vol. 63, No 1, ss. 43 - 48, 1994). W metodzie tej z octanów będących pochodnymi kwasu szikimowego uzyskuje się alkohole, wykorzystując do biotransformacji zawiesiny komórkowe, bądź całe rośliny wyższe.Many methods for the hydrolysis of acetates by chemical means are well known. Their hydrolysis by biotransformation using higher plants is also known. (A. Mironowicz, K. Kromer, P. Pawłowicz, A. Siewiński, "Abilities of some higher planst to hydrolyze the acetates of phenols and aromatic-aliphatic alcohols", Acta Soc. Bot. Polon., Vol. 63, No 1 , pp. 43-48, 1994). In this method, alcohols are obtained from acetates derived from shikimic acid, using cell suspensions or whole higher plants for biotransformation.
Znany jest także sposób prowadzenia biotransformacji, w którym do hydrolizy substratów np. związków steroidowych, terpenów lub pochodnych kwasu szikimowego wykorzystuje się układy enzymnatyczne znajdujące się w rozdrobnionej masie jabłek (opisy patentowe: PL 179959, PL 180763 i PL 183290 oraz publikacja A. Mironowicz, K. Kromer, „Apple-tree shoots and transformed carrot and apple roots used as biocatalysts in enantioselective acetate hydrolysis, alcohol oxidation and ketone reduction”, Collect. Czech. Chem. Commun. Vol. 63, ss. 1655 - 1662, 1998) lub warzyw (opis patentowy: PL 183456 i publikacje: Nguyen Cia Chan, Z. Prochazka, „Saponification of esters of steroid acids and some other esters by potato tuber slices and some other plant tissues”. Coll. Czech. Commun., vol. 38, ss. 227 - 234, 1973; Agnieszka Mironowicz „Biotransformations of racemic acetates by potato and topinambur tubers”, Phytochemistry vol. 47, ss. 1531 - 1534, 1998).There is also a known method of biotransformation, in which enzymatic systems found in the comminuted mass of apples are used for the hydrolysis of substrates, e.g. steroid compounds, terpenes or derivatives of shikimic acid (patents: PL 179959, PL 180763 and PL 183290 and the publication by A. Mironowicz, K. Kromer, "Apple-tree shoots and transformed carrot and apple roots used as biocatalysts in enantioselective acetate hydrolysis, alcohol oxidation and ketone reduction", Collect. Czech. Chem. Commun. Vol. 63, pp. 1655 - 1662, 1998) or vegetables (patent description: PL 183456 and publications: Nguyen Cia Chan, Z. Prochazka, "Saponification of esters of steroid acids and some other esters by potato tuber slices and some other plant tissues". Coll. Czech. Commun., vol. 38, pp. 227-234, 1973; Agnieszka Mironowicz "Biotransformations of racemic acetates by potato and topinambur tubers", Phytochemistry vol. 47, pp. 1531-1534, 1998).
Istota wynalazku polega na tym, że substrat, którym jest racemiczny octan (±)-1-(3-metoksyfenylo)etylu albo octan S-(±)-1-(3-bromofenylo)etylu poddaje się hydrolizie rozdrobnioną masą marchwi.The essence of the invention lies in the fact that the substrate, which is racemic (±) -1- (3-methoxyphenyl) ethyl acetate or S- (±) -1- (3-bromophenyl) ethyl acetate, is hydrolyzed with the comminuted carrot mass.
Korzystnie jest gdy substrat dodaje się do masy roślinnej, która jest zawiesiną w buforze fosforanowym o pH w granicach 4,5 - 6,8.Preferably, the substrate is added to the plant mass which is a suspension in a phosphate buffer with a pH in the range 4.5 - 6.8.
Korzystnie też jest, gdy do 50 ml buforu fosforanowego zawierającego 0,5 - 2,0 g masy roślinnej, w przeliczeniu na suchą masę, dodaje się 10 - 40 mg substratu rozpuszczonego w 0,5 ml acetonu.It is also preferred that 10-40 mg of substrate dissolved in 0.5 ml of acetone are added to 50 ml of phosphate buffer containing 0.5-2.0 g of plant weight, based on dry weight.
Nieoczekiwanie okazało się, że z mieszaniny racemicznej substratu hydrolizuje prawie wyłącznie jeden tylko R-(+)-enancjomer, a drugi S-(-)-enancjomer pozostaje w mieszaninie poreakcyjnej i może być stamtąd wyodrębniony metodą chromatografii kolumnowej.Surprisingly, it turned out that almost exclusively one R - (+) - enantiomer is hydrolyzed from the racemic mixture of the substrate, and the other S - (-) - enantiomer remains in the reaction mixture and can be separated therefrom by means of column chromatography.
Zaletą sposobu według wynalazku jest to, że po procesie biotransformacji w mieszaninie poreakcyjnej pozostaje - oprócz zwykłych produktów hydrolizy, którymi są alkohole - nieprzereagowany prawie wyłącznie jeden z dwóch enancjomerów, mianowicie octan S-(-)-1-(3-metoksyfenylo)etylu albo octan S-(-)-1-(3-bromofenylo)etylu.The advantage of the process according to the invention is that, after the biotransformation process, in the post-reaction mixture, apart from the usual hydrolysis products, which are alcohols, almost exclusively one of the two enantiomers, namely S - (-) - 1- (3-methoxyphenyl) ethyl acetate or S - (-) - 1- (3-bromophenyl) ethyl acetate.
Przedmiot wynalazku jest bliżej objaśniony na przykładach wykonania.The subject of the invention is explained in more detail on the basis of working examples.
P r z y k ł a d 1.P r z k ł a d 1.
Zdrowy i nieuszkodzony korzeń marchwi dokładnie myje się szczotką w ciepłej wodzie z mydł em, po czym rozdrabnia si ę przy pomocy elektrycznego miksera „Malakser”, przez okres okoł o 1 minuty. Tak otrzymaną masę roślinną, w ilości 1,0 g - w przeliczeniu na suchą masę - umieszcza się w kolbie stoż kowej, w której znajduje się 50 ml roztworu buforowego o pH = 6,2.A healthy and undamaged carrot root is thoroughly washed with a brush in warm soapy water and then shredded with an electric mixer "Maker" for about 1 minute. The thus obtained vegetable mass, in the amount of 1.0 g - calculated as dry mass - is placed in a conical flask with 50 ml of a buffer solution with pH = 6.2.
Po dokładnym wymieszaniu, do tak przygotowanej zawiesiny, dodaje się 20 mg racemicznego octanu (±)-1-(3-bromofenylo)etylu rozpuszczonego w 0,5 ml acetonu. Po 48 godzinnej transformacji, następuje hydroliza prawie wyłącznie jednego tylko enancjomeru, to jest octanu R-(+)-1-(3-bromofenylo)etylu do alkoholu, będącego mieszaniną enancjomerycznych alkoholi, których łącznie powstaje 85%. Drugi enancjomeryczny octan, to jest S-(-)-1-(3-bromofenylo)etylu, pozostaje nieprzereagowany w iloś ci 15%.After thorough mixing, 20 mg of racemic (±) -1- (3-bromophenyl) ethyl acetate dissolved in 0.5 ml of acetone are added to the thus prepared suspension. After the 48 hour transformation, almost only one enantiomer is hydrolyzed, i.e. R - (+) - 1- (3-bromophenyl) ethyl acetate to an alcohol which is a mixture of enantiomeric alcohols for a total of 85%. The second enantiomeric acetate, S - (-) - 1- (3-bromophenyl) ethyl, remains 15% unreacted.
Produkty transformacji ekstrahuje się chloroformem, rozdziela na kolumnie chromatograficznej i identyfikuje przez porównanie z wzorcami, stosują c chromatografię gazową , analizę spektralną IR oraz polarymetrię.Transformation products are extracted with chloroform, separated by column chromatography, and identified by comparison with standards using gas chromatography, IR spectral analysis, and polarimetry.
Chromatografię gazową (GC Hewlett Packard 5890; FID, gaz nośny wodór) wykonuje się na chiralnej kolumnie Chiralsil-Dex CB; 25m.Gas chromatography (GC Hewlett Packard 5890; FID, hydrogen carrier gas) is performed on a chiral Chiralsil-Dex CB column; 25m.
Dane fizyczne otrzymanego związku są następujące:The physical data of the obtained compound are as follows:
IR ν (cm-1): 3000, 1752, 1580, 1436, 1376, 1244, 680.IR ν (cm -1 ): 3000, 1752, 1580, 1436, 1376, 1244, 680.
PL 203 020 B1PL 203 020 B1
Skręcalność właściwa, mierzona w chloroformie dla octanu S-(-)-1-(3-bromofenylo)etylu, jest ujemna, a Rt w chromatografii gazowej - dłuższy.The specific rotation, measured in chloroform, for S - (-) - 1- (3-bromophenyl) ethyl acetate is negative and Rt in gas chromatography is longer.
P r z y k ł a d 2.P r z k ł a d 2.
Masę roślinną otrzymaną tak jak w przykładzie 1, w ilości 1,0 g - w przeliczeniu na suchą masę - umieszcza się w kolbie stoż kowej, w której znajduje się 50 ml roztworu buforowego o pH = 6,2.The vegetable mass obtained as in Example 1, in the amount of 1.0 g - calculated on the dry mass - is placed in a conical flask with 50 ml of a buffer solution with pH = 6.2.
Po dokładnym wymieszaniu, do tak przygotowanej zawiesiny, dodaje się 20 mg racemicznego octanu (±)-1-(3-metoksyfenylo)etylu rozpuszczonego w 0,5 ml acetonu. Po 48 godzinnej transformacji, następuje hydroliza prawie wyłącznie jednego tylko enancjomeru, to jest octanu R-(+)-1-(3-metoksyfenylo)etylu do alkoholu, będącego mieszaniną enancjomerycznych alkoholi, których łącznie powstaje 74%. Drugi enancjomeryczny octan, to jest S-(-)-1-(3-metoksyfenylo)etylu, pozostaje nieprzereagowany w ilości 26%.After thorough mixing, 20 mg of racemic (±) -1- (3-methoxyphenyl) ethyl acetate dissolved in 0.5 ml of acetone are added to the thus prepared suspension. After the 48 hour transformation, almost only one enantiomer is hydrolyzed, i.e. R - (+) - 1- (3-methoxyphenyl) ethyl acetate to an alcohol which is a mixture of enantiomeric alcohols for a total of 74%. The second enantiomeric acetate, S - (-) - 1- (3-methoxyphenyl) ethyl, remains unreacted at 26%.
Produkty transformacji ekstrahuje się chloroformem, rozdziela na kolumnie chromatograficznej i identyfikuje przez porównanie z wzorcami, stosują c chromatografię gazową , analizę spektralną IR oraz polarymetrię. Chromatografię gazową (GC Hewlett Packard 5890; FID, gaz nośny wodór) wykonuje się na chiralnej kolumnie Chiralsil-Dex CB; 25m.Transformation products are extracted with chloroform, separated by column chromatography, and identified by comparison with standards using gas chromatography, IR spectral analysis, and polarimetry. Gas chromatography (GC Hewlett Packard 5890; FID, hydrogen carrier gas) is performed on a chiral Chiralsil-Dex CB column; 25m.
Dane fizyczne otrzymanego związku są następujące:The physical data of the obtained compound are as follows:
IR ν (cm-1): 1760, 1245, 800.IR ν (cm -1 ): 1760, 1245, 800.
Skręcalność właściwa, mierzona w chloroformie dla octanu S-(-)-1-(3-metoksyfenylo)etylu, jest ujemna, a Rt w chromatografii gazowej - dłuższy.The specific rotation, measured in chloroform, for S - (-) - 1- (3-methoxyphenyl) ethyl acetate is negative and Rt is longer in gas chromatography.
Claims (3)
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| PL368393A PL203020B1 (en) | 2004-06-04 | 2004-06-04 | Method for obtaining ethyl (3-metoxyphenyl)-1-(-)-S acetate and ethyl (3-bromophenyl)-1-(-)S acetate by biotransformation |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| PL368393A PL203020B1 (en) | 2004-06-04 | 2004-06-04 | Method for obtaining ethyl (3-metoxyphenyl)-1-(-)-S acetate and ethyl (3-bromophenyl)-1-(-)S acetate by biotransformation |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| PL368393A1 PL368393A1 (en) | 2004-11-29 |
| PL203020B1 true PL203020B1 (en) | 2009-08-31 |
Family
ID=34271274
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| PL368393A PL203020B1 (en) | 2004-06-04 | 2004-06-04 | Method for obtaining ethyl (3-metoxyphenyl)-1-(-)-S acetate and ethyl (3-bromophenyl)-1-(-)S acetate by biotransformation |
Country Status (1)
| Country | Link |
|---|---|
| PL (1) | PL203020B1 (en) |
-
2004
- 2004-06-04 PL PL368393A patent/PL203020B1/en unknown
Also Published As
| Publication number | Publication date |
|---|---|
| PL368393A1 (en) | 2004-11-29 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| Vick et al. | Biosynthesis of jasmonic acid by several plant species | |
| Bouwmeester et al. | Enantiomeric composition of carvone, limonene, and carveols in seeds of dill and annual and biennial caraway varieties | |
| US6417339B1 (en) | Dendrimers based on saccharides | |
| TW200920263A (en) | Method of producing hard butter | |
| PL97902B1 (en) | AGENT REGULATING THE GROWTH OF PLANTS | |
| EP0555466B1 (en) | Process for the production of natural vanilla extract by enzymatic processing of green vanilla pods, and extract thereby obtained | |
| EP0971586A1 (en) | Composition and method for stimulating pollen germination | |
| Inamdar et al. | Innovative use of intact seeds of Mucuna monosperma Wight for improved yield of L-DOPA | |
| JP3294860B2 (en) | Method for producing optically active alcohol | |
| Bruni et al. | Plants-mediated reduction in the synthesis of homochiral secondary alcohols | |
| PL179959B1 (en) | Method for obtaining R - (+) - 1- (2-naphthyl) ethyl acetate. / | |
| PL180763B1 (en) | Method of obtaining r-(+)-1(1-naphtyl)etylacetate | |
| PL180792B1 (en) | Method of obtaining r-(+)-1-phenylethyl | |
| PL194402B1 (en) | Method of obtaining s-(-)-1-phenylethanol by biotransformation | |
| PL204256B1 (en) | Method for obtaining S - (-) - 1 - (2 - bromophenyl) ethanol by biotransformation | |
| PL194403B1 (en) | Method of obtaining r-(+)-1-phenylethanol by biotransformation | |
| Schirbel et al. | [123/131I] Iodometomidate as a radioligand for functional diagnosis of adrenal disease: synthesis, structural requirements and biodistribution | |
| EP0481147B1 (en) | Process for the preparation of cis-3-hexene-1-ol from unsaturated fatty acids | |
| PL204686B1 (en) | Method for obtaining S-(-)-1-(3-bromophenyl) ethanol and S-(-)-1-(3-metoxyphenyl) ethanol by biotransformation | |
| PL194398B1 (en) | Method of obtaining s-(-)-1-(2-napthyl) ethanol by biotransformation | |
| PL179812B1 (en) | Method for obtaining S - (-) - 1- (1-naphthyl) ethanol by biotransformation | |
| US5620879A (en) | Process for producing natural cis-3-hexenol from unsaturated fatty acids | |
| PL179778B1 (en) | Method of obtaining S - (-) - 1-phenylethanol by biotransformation | |
| ASGHARI et al. | Biotransformation of aromatic aldehydes by cell cultures of Peganum harmala L. and Silybum marianum (L.) Gaertn | |
| PL204257B1 (en) | Method for obtaining S-(-)-1-(3-metoxyphenyl) ethanol by biotransformation |