PL222199B1 - Process for preparing (-)-trans-5-(1-hydroxy-3-methylbutyl) -4 - methyltetrahydrofuran-2-one - Google Patents
Process for preparing (-)-trans-5-(1-hydroxy-3-methylbutyl) -4 - methyltetrahydrofuran-2-oneInfo
- Publication number
- PL222199B1 PL222199B1 PL404755A PL40475513A PL222199B1 PL 222199 B1 PL222199 B1 PL 222199B1 PL 404755 A PL404755 A PL 404755A PL 40475513 A PL40475513 A PL 40475513A PL 222199 B1 PL222199 B1 PL 222199B1
- Authority
- PL
- Poland
- Prior art keywords
- trans
- substrate
- formula
- methyltetrahydrofuran
- methylbutyl
- Prior art date
Links
- IMDDONRMSFVBSE-HUWCLSLFSA-N (4R,5R)-5-(1-hydroxy-3-methylbutyl)-4-methyloxolan-2-one Chemical compound OC(CC(C)C)[C@H]1[C@@H](CC(O1)=O)C IMDDONRMSFVBSE-HUWCLSLFSA-N 0.000 title claims description 8
- 238000004519 manufacturing process Methods 0.000 title description 2
- 238000000034 method Methods 0.000 claims description 13
- 239000000758 substrate Substances 0.000 claims description 9
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical group ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 claims description 8
- 230000008569 process Effects 0.000 claims description 7
- 230000009466 transformation Effects 0.000 claims description 7
- 244000286779 Hansenula anomala Species 0.000 claims description 6
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 claims description 5
- 230000000813 microbial effect Effects 0.000 claims description 5
- 239000002904 solvent Substances 0.000 claims description 5
- 238000004587 chromatography analysis Methods 0.000 claims description 4
- 239000012043 crude product Substances 0.000 claims description 4
- 238000006243 chemical reaction Methods 0.000 claims description 3
- 150000001875 compounds Chemical class 0.000 claims description 3
- 238000006704 dehydrohalogenation reaction Methods 0.000 claims description 3
- 239000007788 liquid Substances 0.000 claims description 3
- 230000007246 mechanism Effects 0.000 claims description 3
- 230000002906 microbiologic effect Effects 0.000 claims description 3
- 238000002360 preparation method Methods 0.000 claims description 3
- 239000003153 chemical reaction reagent Substances 0.000 claims description 2
- 238000000605 extraction Methods 0.000 claims description 2
- 229910052943 magnesium sulfate Inorganic materials 0.000 claims description 2
- 235000019341 magnesium sulphate Nutrition 0.000 claims description 2
- 239000003960 organic solvent Substances 0.000 claims description 2
- 238000013048 microbiological method Methods 0.000 claims 1
- 230000000644 propagated effect Effects 0.000 claims 1
- 239000007858 starting material Substances 0.000 claims 1
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 2
- 239000003480 eluent Substances 0.000 description 2
- KDCIHNCMPUBDKT-UHFFFAOYSA-N hexane;propan-2-one Chemical compound CC(C)=O.CCCCCC KDCIHNCMPUBDKT-UHFFFAOYSA-N 0.000 description 2
- 239000000203 mixture Substances 0.000 description 2
- 239000000047 product Substances 0.000 description 2
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- 239000004593 Epoxy Substances 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
- 235000014683 Hansenula anomala Nutrition 0.000 description 1
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- 239000002537 cosmetic Substances 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- 235000013305 food Nutrition 0.000 description 1
- 239000002778 food additive Substances 0.000 description 1
- 235000013373 food additive Nutrition 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 238000007273 lactonization reaction Methods 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 102220201851 rs143406017 Human genes 0.000 description 1
- 239000000741 silica gel Substances 0.000 description 1
- 229910002027 silica gel Inorganic materials 0.000 description 1
- 230000003595 spectral effect Effects 0.000 description 1
- 238000000844 transformation Methods 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
Landscapes
- Preparation Of Compounds By Using Micro-Organisms (AREA)
Description
(12) OPIS PATENTOWY (19) PL (11) 222199 (13) B1 (21) Numer zgłoszenia: 404755 (51) Int.Cl.(12) PATENT DESCRIPTION (19) PL (11) 222199 (13) B1 (21) Application number: 404755 (51) Int.Cl.
C12P 17/04 (2006.01) C12R 1/72 (2006.01) (22) Data zgłoszenia: 18.07.2013C12P 17/04 (2006.01) C12R 1/72 (2006.01) (22) Date of notification: 18/07/2013
Sposób wytwarzania (-)-trans-5-(1-hydroksy-3-metylobutylo)-4-metylotetrahydrofuran-2-onuMethod for producing (-) - trans-5- (1-hydroxy-3-methylbutyl) -4-methyltetrahydrofuran-2-one
PL 222 199 B1PL 222 199 B1
Opis wynalazkuDescription of the invention
Przedmiotem wynalazku jest sposób wytwarzania (-)-trans-5-(1-hydroksy-3-metylobutylo)-4-metylotetrahydrofuran-2-onu o wzorze 2 przedstawionym na rysunku.The subject of the invention is a process for the preparation of (-) - trans-5- (1-hydroxy-3-methylbutyl) -4-methyltetrahydrofuran-2-one of the formula 2 shown in the drawing.
Związek ten dzięki swym interesującym właściwościom zapachowym może znaleźć zastosowanie w przemyśle kosmetycznym oraz spożywczym, np. jako dodatek do żywności.Due to its interesting aroma properties, this compound can be used in the cosmetics and food industries, e.g. as a food additive.
Związek ten jest znany w literaturze i został otrzymany na drodze mikrobiologicznych transformacji racemicznych γ,δ-epoksyestrów, opisanych przez Olejniczak T. i wsp. (Olejniczak, T.,This compound is known in the literature and was obtained by microbiological transformations of racemic γ, δ-epoxyesters described by Olejniczak T. et al. (Olejniczak, T.,
Gawroński, J., Wawrzeńczyk, C. Lactones 6. Microbial Lactonization of γ,δ-Epoxy Esters. ChiralityGawroński, J., Wawrzeńczyk, C. Lactones 6. Microbial Lactonization of γ, δ-Epoxy Esters. Chirality
2001, 13 (6), 302-307). Otrzymany został w postaci oleistej cieczy o skręcalności [a] 589= -8.9 (c=0.5; CHCl3), z dobrą czystością optyczną, de=11%.2001, 13 (6), 302-307). It was obtained in the form of an oily liquid with rotation [a] 589 = -8.9 (c = 0.5; CHCl3), with good optical purity, de = 11%.
Wynalazek dotyczy mikrobiologicznego sposobu wytwarzania (-)-trans-5-(1 -hydroksy-3-metylobutylo)-4-metylotetrahydrofuran-2-onu na drodze jednoetapowej reakcji mikrobiologicznej mechanizmu dehydrohalogenacji i translaktonizacji substratu, którym jest trans, trans-5-jodo-4-metylo-6-(2-metylopropylo)tetrahydro-2H-piran-2-on. Drożdże z gatunku Candida pelliculosa, namnaża się w płynnym podłożu mikrobiologicznym, charakterystycznym dla tego rodzaju, przy ciągłym mieszaniu reagentów, w temperaturze 20-30°C. Do narośniętej hodowli dodaje się substrat w stężeniu od 150 mg/L do 350 mg/L i dalej prowadzi się proces, aż do całkowitego zużycia substratu, po czym po zakończeniu transformacji roztwór transformacyjny ekstrahuje się rozpuszczalnikami organicznymi niemieszającymi się z wodą, oddziela frakcję organiczną, osusza bezwodnym siarczanem magnezu, odparowuje rozpuszczalnik i tak otrzymany surowy produkt oczyszcza się za pomocą technik chromatograficznych.The invention relates to a microbial method of producing (-) - trans-5- (1-hydroxy-3-methylbutyl) -4-methyltetrahydrofuran-2-one by a one-step microbial reaction of the dehydrohalogenation and translactonization mechanism of the trans, trans-5-iodo substrate. -4-methyl-6- (2-methylpropyl) tetrahydro-2H-pyran-2-one. Yeasts of the Candida pelliculosa species are multiplied in a liquid microbiological medium, characteristic for this type, with constant mixing of the reagents at a temperature of 20-30 ° C. The substrate is added to the grown culture in a concentration from 150 mg / L to 350 mg / L and the process is continued until the substrate is completely consumed, then, after completion of the transformation, the transformation solution is extracted with organic solvents immiscible with water, and the organic fraction is separated, is dried with anhydrous magnesium sulfate, the solvent is evaporated off and the crude product thus obtained is purified by chromatographic techniques.
Korzystnie jest, gdy proces prowadzi się w temperaturze 28°C.It is preferable that the process is carried out at a temperature of 28 ° C.
Korzystnie także jest, gdy do hodowli dodaje się substrat w stężeniu 200 mg/L.It is also preferred that the substrate is added to the culture in a concentration of 200 mg / L.
Korzystnie również jest, że rozpuszczalnikiem stosowanym do ekstrakcji jest chloroform.It is also preferred that the extraction solvent is chloroform.
Postępując zgodnie z wynalazkiem, w wyniku działania układu enzymatycznego zawartego w żywych komórkach kultury Candida pelliculosa, następuje reakcja jednoetapowego mechanizmu dehydrohalogenacji i translaktonizacji substratu.By following the invention, as a result of the action of the enzyme system contained in living cells of Candida pelliculosa culture, the reaction of a one-step mechanism of dehydrohalogenation and translactonization of the substrate occurs.
Zasadniczą zaletą wynalazku jest otrzymanie, w łagodnych warunkach (-)-trans-5-(1 -hydroksy-3-metylobutylo)-4-metylotetrahydrofuran-2-onu, z wydajnością 55%.The main advantage of the invention is the preparation of (-) - trans-5- (1-hydroxy-3-methylbutyl) -4-methyltetrahydrofuran-2-one under mild conditions with a yield of 55%.
Wynalazek jest bliżej objaśniony w przykładach wykonania.The invention is explained in more detail in the working examples.
P r z y k ł a d 1. Do kolby o pojemności 300 cm3, w której znajduje się 100 cm3 sterylnej pożywki zawierającej 3 g glukozy i 1 g aminobaku, wprowadza się drożdże Candida pelliculosa. Po 2 dniach wzrostu drobnoustrojów w temperaturze 28°C i przy ciągłym wstrząsaniu, dodaje się 20 mg trans, 3 trans-5-jodo-4-metylo-6-(2-metylopropylo)tetrahydro-2H-piran-2-onu, o wzorze 1, rozpuszczonego w 1 cm3 acetonu. Transformację prowadzi się przy ciągłym wstrząsaniu przez 5 dni. Następnie, uzyskany roztwór transformacyjny ekstrahuje się trzykrotnie chloroformem, osusza siarczanem magnezu i odparowuje rozpuszczalnik. Otrzymuje się 17 mg surowego produktu, który oczyszcza się chromatograficznie, używając jako eluentu mieszaniny heksan - aceton w stosunku 6:1.EXAMPLE 1 To a flask of 300 cm 3, which is 100 cm 3 of sterile medium containing 3 g of glucose and 1 g aminobaku introduced into yeast Candida pelliculosa. After 2 days of microbial growth at 28 ° C and with continuous shaking, 20 mg of trans, 3 trans-5-iodo-4-methyl-6- (2-methylpropyl) tetrahydro-2H-pyran-2-one are added, formula 1 dissolved in 1 cm 3 of acetone. The transformation is carried out under continuous shaking for 5 days. Thereafter, the resulting transformation solution was extracted three times with chloroform, dried with magnesium sulfate and the solvent was evaporated. 17 mg of crude product are obtained, which product is purified by chromatography using a hexane-acetone mixture in the ratio of 6: 1 as eluent.
Na tej drodze otrzymuje się 7 mg (-)-trans-5-(1-hydroksy-3-metylobutylo)-4-metylotetrahydrofuran-2-onu (wydajność 55%).In this way, 7 mg of (-) - trans-5- (1-hydroxy-3-methylbutyl) -4-methyltetrahydrofuran-2-one are obtained (55% yield).
P r z y k ł a d 2. Postępuje się jak w przykładzie 1, z tym że stężenie substratu w mieszaninie reakcyjnej wynosi 350 mg/L. Otrzymuje się 30 mg surowego produktu, który oczyszcza się chromatograficznie na żelu krzemionkowym, stosując jako eluent mieszaninę heksan - aceton w stosunku 6:1.Example 2 The procedure of Example 1 is followed, except that the substrate concentration in the reaction mixture is 350 mg / L. 30 mg of crude product are obtained, which are purified by chromatography on silica gel using a hexane-acetone mixture in the ratio of 6: 1 as eluent.
W ten sposób otrzymuje się 17 mg (-)-trans-5-(1-hydroksy-3-metylobutylo)-4-metylotetrahydrofuran-2-onu (wydajność 55%).Thus, 17 mg of (-) - trans-5- (1-hydroxy-3-methylbutyl) -4-methyltetrahydrofuran-2-one are obtained (55% yield).
Uzyskany produkt charakteryzuje się następującymi danymi spektralnymi:The obtained product is characterized by the following spectral data:
IR (film, cm-1): 3396 (s), 1789 (s), 1146 (m);IR (movie, cm -1 ): 3396 (s), 1789 (s), 1146 (m);
1H NMR (300 MHz, CDCI3) δ: 0.93 i 0.97 (dwa d, J = 6.6 Hz, 6H, -CH(CH3)2), 1.13 (d, J = 7.1 Hz, 3H, CH3-4), 1.44 (ddd, J = 14.1,9.9, 4.5 Hz, 1H, jeden z CH2-2'), 1.56 (ddd, J = 14.1, 10.4, 2.6 Hz, 1H, jeden z CH2-2'), 1.77 (bs, 1H, -OH), 1.84 (m, 1H, H-3'), 2.24 (m, 1H, jeden z CH2-3), 2.69-2.75 (m, 2H, jeden z CH2-3, H-4), 3.68 (ddd, J = 10.4, 8.0, 2.6 Hz, 1H, H-1'), 4.14 (dd, J = 8.0, 5.2 Hz, 1H, H-5); 1 H NMR (300 MHz, CDCl 3) δ: 0.93 and 0.97 (two d, J = 6.6 Hz, 6H, -CH (CH 3 ) 2 ), 1.13 (d, J = 7.1 Hz, 3H, CH3-4), 1.44 (ddd, J = 14.1,9.9, 4.5 Hz, 1H, one of CH 2 -2 '), 1.56 (ddd, J = 14.1, 10.4, 2.6 Hz, 1H, one of CH2-2'), 1.77 (bs , 1H, -OH), 1.84 (m, 1H, H-3 '), 2.24 (m, 1H, one of CH2-3), 2.69-2.75 (m, 2H, one of CH2-3, H-4) , 3.68 (ddd, J = 10.4, 8.0, 2.6 Hz, 1H, H-1 '), 4.14 (dd, J = 8.0, 5.2 Hz, 1H, H-5);
13C NMR (75,5 MHz, CDCI3) δ: 14.22 (CH3-4), 21.49 i 23.78 (-CHCCHsh), 24.22 (C-3'), 32.00 (C-4), 38.02 (C-3), 43.65 (C-1'), 67.96 (C-2'), 84.99 (C-5), 176.78 (C-2). 13 C NMR (75.5 MHz, CDCl 3) δ: 14.22 (CH 3 -4), 21.49 and 23.78 (-CHCCHsh), 24.22 (C-3 '), 32.00 (C-4), 38.02 (C-3) , 43.65 (C-1 '), 67.96 (C-2'), 84.99 (C-5), 176.78 (C-2).
PL 222 199 B1PL 222 199 B1
Claims (4)
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| PL404755A PL222199B1 (en) | 2013-07-18 | 2013-07-18 | Process for preparing (-)-trans-5-(1-hydroxy-3-methylbutyl) -4 - methyltetrahydrofuran-2-one |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| PL404755A PL222199B1 (en) | 2013-07-18 | 2013-07-18 | Process for preparing (-)-trans-5-(1-hydroxy-3-methylbutyl) -4 - methyltetrahydrofuran-2-one |
Publications (2)
| Publication Number | Publication Date |
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| PL404755A1 PL404755A1 (en) | 2014-01-20 |
| PL222199B1 true PL222199B1 (en) | 2016-07-29 |
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| Application Number | Title | Priority Date | Filing Date |
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| PL404755A PL222199B1 (en) | 2013-07-18 | 2013-07-18 | Process for preparing (-)-trans-5-(1-hydroxy-3-methylbutyl) -4 - methyltetrahydrofuran-2-one |
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| Publication number | Publication date |
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| PL404755A1 (en) | 2014-01-20 |
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