PL236837B1 - trans-(4S,5R,6S)-5-(1-Bromoethyl)-4-(2',5'-dimethylphenyl)-dihydrofuran-2-one and method of its preparation - Google Patents
trans-(4S,5R,6S)-5-(1-Bromoethyl)-4-(2',5'-dimethylphenyl)-dihydrofuran-2-one and method of its preparation Download PDFInfo
- Publication number
- PL236837B1 PL236837B1 PL426970A PL42697018A PL236837B1 PL 236837 B1 PL236837 B1 PL 236837B1 PL 426970 A PL426970 A PL 426970A PL 42697018 A PL42697018 A PL 42697018A PL 236837 B1 PL236837 B1 PL 236837B1
- Authority
- PL
- Poland
- Prior art keywords
- dimethylphenyl
- dihydrofuran
- bromoethyl
- trans
- formula
- Prior art date
Links
- 238000000034 method Methods 0.000 title claims abstract description 14
- 238000002360 preparation method Methods 0.000 title abstract description 6
- AVSAPYYIFVSGNF-ITKZLYELSA-N (E,3R)-3-(2,5-dimethylphenyl)hex-4-enoic acid Chemical compound CC1=C(C=C(C=C1)C)[C@H](CC(=O)O)\C=C\C AVSAPYYIFVSGNF-ITKZLYELSA-N 0.000 claims abstract description 7
- 238000010722 bromolactonization reaction Methods 0.000 claims abstract description 6
- 239000000203 mixture Substances 0.000 claims abstract description 6
- 239000002253 acid Substances 0.000 claims abstract description 3
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 9
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 6
- -1 4- (2 ', 5'-dimethylphenyl) -dihydrofuran-2-one Chemical compound 0.000 claims description 5
- 238000004440 column chromatography Methods 0.000 claims description 3
- 125000006083 1-bromoethyl group Chemical group 0.000 claims description 2
- 230000003197 catalytic effect Effects 0.000 claims description 2
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 2
- 150000001875 compounds Chemical class 0.000 abstract description 5
- 230000001093 anti-cancer Effects 0.000 abstract 1
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 9
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 6
- 238000000338 in vitro Methods 0.000 description 5
- 241000282465 Canis Species 0.000 description 4
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 3
- PCLIMKBDDGJMGD-UHFFFAOYSA-N N-bromosuccinimide Chemical compound BrN1C(=O)CCC1=O PCLIMKBDDGJMGD-UHFFFAOYSA-N 0.000 description 3
- 230000001028 anti-proliverative effect Effects 0.000 description 3
- 208000004736 B-Cell Leukemia Diseases 0.000 description 2
- 208000003950 B-cell lymphoma Diseases 0.000 description 2
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 2
- 238000006243 chemical reaction Methods 0.000 description 2
- 239000012528 membrane Substances 0.000 description 2
- 201000008968 osteosarcoma Diseases 0.000 description 2
- 239000000523 sample Substances 0.000 description 2
- 210000004881 tumor cell Anatomy 0.000 description 2
- 238000005160 1H NMR spectroscopy Methods 0.000 description 1
- RSMFTPWQSUSOGH-VUDGCMKMSA-N CC1=C(C=C(C=C1)C)[C@H](CC)\C=C\C Chemical compound CC1=C(C=C(C=C1)C)[C@H](CC)\C=C\C RSMFTPWQSUSOGH-VUDGCMKMSA-N 0.000 description 1
- 206010018910 Haemolysis Diseases 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
- 238000005481 NMR spectroscopy Methods 0.000 description 1
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical class [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 1
- 239000002246 antineoplastic agent Substances 0.000 description 1
- 229940041181 antineoplastic drug Drugs 0.000 description 1
- 239000012267 brine Substances 0.000 description 1
- 210000004027 cell Anatomy 0.000 description 1
- 230000003833 cell viability Effects 0.000 description 1
- 239000007795 chemical reaction product Substances 0.000 description 1
- 238000007398 colorimetric assay Methods 0.000 description 1
- 230000001472 cytotoxic effect Effects 0.000 description 1
- 239000002274 desiccant Substances 0.000 description 1
- 230000001066 destructive effect Effects 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 239000003480 eluent Substances 0.000 description 1
- 210000003743 erythrocyte Anatomy 0.000 description 1
- 210000003617 erythrocyte membrane Anatomy 0.000 description 1
- 230000008588 hemolysis Effects 0.000 description 1
- 230000002209 hydrophobic effect Effects 0.000 description 1
- 230000001900 immune effect Effects 0.000 description 1
- 230000003993 interaction Effects 0.000 description 1
- 150000002596 lactones Chemical class 0.000 description 1
- JHDGGIDITFLRJY-UHFFFAOYSA-N laurdan Chemical compound C1=C(N(C)C)C=CC2=CC(C(=O)CCCCCCCCCCC)=CC=C21 JHDGGIDITFLRJY-UHFFFAOYSA-N 0.000 description 1
- 208000032839 leukemia Diseases 0.000 description 1
- 150000002632 lipids Chemical class 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 210000002540 macrophage Anatomy 0.000 description 1
- 238000012544 monitoring process Methods 0.000 description 1
- 239000012044 organic layer Substances 0.000 description 1
- 230000010287 polarization Effects 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 239000000741 silica gel Substances 0.000 description 1
- 229910002027 silica gel Inorganic materials 0.000 description 1
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 238000004611 spectroscopical analysis Methods 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
Landscapes
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
Przedmiotem zgłoszenia jest trans-(4S,5R,6S)-5-(1-bromoetylo)-4-(2',5'-dimetylofenylo)-dihydrofuran-2-on oraz sposób jego otrzymywania o wzorze 1. Powyższy sposób dotyczy optycznie czynnego trans-(4S,5R,6S)-5-(1-bromoetylo)-4-(2',5'-dimetylofenylo)-dihydrofuran-2-onu o wzorze 1 przedstawionym na rysunku oraz sposobu jego otrzymywania. Sposób otrzymywania optycznie czynnego tans-(4S,5R,6S)-5-(1-bromoetylo)-4-(2',5'-dimetylofenylo)-dihydrofuran-2-onu polega na tym, że kwas (R,E)-3-(2',5'-dimetylofenylo)-heks-4-enowy poddaje się reakcji bromolaktonizacji otrzymując mieszaninę produktów, z której następnie metodą chromatografii kolumnowej wydziela się w postaci czystej trans-(4S,5R,6S)-5-(1-bromoetylo)-4-(2',5'-dimetylofenylo)-dihydrofuran-2-on. Optycznie czynny β-fenylo-δ-bromo-γ-lakton o wzorze 1 może znaleźć zastosowanie w farmacji jako związek o działaniu antynowotworowym.The subject of the application is trans-(4S,5R,6S)-5-(1-bromoethyl)-4-(2',5'-dimethylphenyl)-dihydrofuran-2-one and the method of its preparation of the formula 1. The above method relates optically active trans-(4S,5R,6S)-5-(1-bromoethyl)-4-(2',5'-dimethylphenyl)-dihydrofuran-2-one of the formula 1 shown in the figure and the method of its preparation. The method of obtaining the optically active tans-(4S,5R,6S)-5-(1-bromoethyl)-4-(2',5'-dimethylphenyl)-dihydrofuran-2-one is that the acid (R,E) -3-(2',5'-dimethylphenyl)-hex-4-enoic acid is subjected to a bromolactonization reaction to obtain a mixture of products, from which trans-(4S,5R,6S)-5-( 1-bromoethyl)-4-(2',5'-dimethylphenyl)-dihydrofuran-2-one. The optically active β-phenyl-δ-bromo-γ-lactone of the formula 1 can be used in pharmacy as a compound with anticancer activity.
Description
Przedmiotem wynalazku jest optycznie czynny trans -(4S,5R,6S)-5-(1-bromoetylo)-4-(2',5'-dimetylofenylo)-dihydrofuran-2-on o wzorze 1 przedstawionym na rysunku.The present invention relates to optically active trans - (4S, 5R, 6S) -5- (1-bromoethyl) -4- (2 ', 5'-dimethylphenyl) -dihydrofuran-2-one of the formula 1 shown in the drawing.
Przedmiotem, wynalazku jest również sposób otrzymywania bromolaktonu o wzorze 1 z kwasu (R,E)-3-(2',5'-dimetylofenylo)-heks-4-enowego.The invention also relates to a process for the preparation of a bromolactone of formula I from (R, E) -3- (2 ', 5'-dimethylphenyl) -hex-4-enoic acid.
Związek ten może znaleźć zastosowanie w farmacji jako składnik leków antynowotworowych.This compound can be used in pharmacy as a component of anti-cancer drugs.
Dotychczas z opisów patentów PL229558 oraz PL229559, znane były optycznie czynne jodolaktony z pierścieniem 2,5-dimetylofenylowym, wykazujące aktywność antyproliferacyjną in vitro wobec linii komórkowych: białaczki ludzkiej (Jurkat), psiej białaczki B-komórkowej (GL-1), psiej osteosarkomy (D17) oraz psiego chłoniaka B-komórkowego (CLBL-1).Until now, from the descriptions of patents PL229558 and PL229559, optically active iodolactones with a 2,5-dimethylphenyl ring were known, showing antiproliferative activity in vitro against the following cell lines: human leukemia (Jurkat), canine B-cell leukemia (GL-1), canine osteosarcoma ( D17) and canine B-cell lymphoma (CLBL-1).
Wynalazek dotyczy sposobu wytwarzania na drodze syntezy chemicznej optycznie czynnego trans-(4S,5R,6S)-5-(1-bromoetylo)-4-(2',5'-dimetylofenylo)-dihydrofuran-2-onu o wzorze 1 z kwasu (R,E)-3-(2',5'-dimetylofenylo)-heks-4-enowego. Istota wynalazku polega na tym, że kwas (R,E)-3-(2',5',dimetylofenylo)-heks-4-enowy poddaje się reakcji z N-bromoimidem kwasu bursztynowego, a z otrzymanej mieszaniny bromolaktonów wydziela się metodą chromatografii kolumnowej czysty trans(4S,5R,6S)-5-(1-bromoetylo)-4-(2',5'-dimetylofenylo)-dihydrofuran-2-on oraz jego znane izomery.The invention relates to a process for the preparation by chemical synthesis of optically active trans- (4S, 5R, 6S) -5- (1-bromoethyl) -4- (2 ', 5'-dimethylphenyl) -dihydrofuran-2-one of the formula I from the acid (R, E) -3- (2 ', 5'-dimethylphenyl) -hex-4-ene. The essence of the invention lies in the fact that (R, E) -3- (2 ', 5', dimethylphenyl) -hex-4-enoic acid is reacted with N-bromosuccinimide, and the resulting mixture of bromolactones is separated by column chromatography. pure trans (4S, 5R, 6S) -5- (1-bromoethyl) -4- (2 ', 5'-dimethylphenyl) -dihydrofuran-2-one and its known isomers.
Korzystnie jest, gdy reakcję bromolaktonizacji kwasu (R,E)-3-(2',5'-dimetylofenyIo)-heks-4-enowego prowadzi się w tetrahydrofuranie.Preferably, the bromolactonization reaction of (R, E) -3- (2 ', 5'-dimethylphenyl) -hex-4-enoic acid is carried out in tetrahydrofuran.
Korzystnie jest także, gdy reakcję bromolaktonizacji kwasu (R,E)-3-(2',5'-dimetylofenylo)-heks-4-enowego prowadzi się w obecności katalitycznych ilości kwasu octowego.It is also preferred that the bromolactonization reaction of (R, E) -3- (2 ', 5'-dimethylphenyl) -hex-4-enoic acid is carried out in the presence of catalytic amounts of acetic acid.
Zasadniczą zaletą: wynalazku jest otrzymanie trans -(4S,5R,6S)-5-(1-bromoetylo)-4-(2',5'-dimetylofenylo)-dihydrofuran-2-onu o wzorze 1 wykazującego aktywność antyproliferacyjną in vitro z bardzo wysokim nadmiarem enancjomerycznym (ee = 99%).The main advantage of the invention is the preparation of trans - (4S, 5R, 6S) -5- (1-bromoethyl) -4- (2 ', 5'-dimethylphenyl) -dihydrofuran-2-one of the formula 1 showing antiproliferative activity in vitro from very high enantiomeric excess (ee = 99%).
Wynalazek jest bliżej objaśniony w przykładzie wykonania.The invention is explained in more detail in an exemplary embodiment.
P r z y k ł a d.P r z k ł a d.
W kolbie okrągłodennej umieszcza się 1,19 g kwasu (R,E)-3-(2',5'-dimetylofenylo)-heks-4-enowego, 1,6 g N-bromoimidu kwasu bursztynowego (NBS), 70 cm3 THF i kroplę kwasu octowego. Całość miesza się na mieszadle magnetycznym w temperaturze pokojowej kontrolując przebieg reakcji za pomocą chromatografii cienkowarstwowej heksan : aceton w stosunku objętościowym 3 : 1. Po całkowitym przereagowaniu substratu całość przenosi się do rozdzielacza, rozcieńcza 30 cm3 eteru dietylowego i przemywa nasyconym roztworem NaHCO3 (dwukrotnie po 20 cm3). Warstwę organiczną zobojętnia się solanką wobec papierka wskaźnikowego i osusza bezwodnym siarczanem(VI) magnezu. Po odsączeniu środka suszącego odparowuje się rozpuszczalnik. Otrzymuje się surową mieszaninę bromolaktonów, z której metodą chromatografii kolumnowej na żelu krzemionkowym przy zastosowaniu jako eluentu mieszaniny heksan : aceton w stosunku objętościowym 20 : 1 wydziela się jako jeden z produktów trans -(4S,5R,6S)-5-(1-bromoetylo)-4-(2',5'-dimetylofenylo)-dihydrofuran-2-on w ilości 0,174 g (11% wydajności teoretycznej). Pozostałe produkty reakcji stanowią znane izomery otrzymanego związku, tj. (4S,5S,6R)-5-1-bromo-4-r-(2',5'-dimetylofenylo)-6-c-metylotetrahydropiran-2-on oraz cis -(4S,5S,6R)-5-(1-bromoetylo)-4-(2',5'-dimetylofenylo)-dihydrofuran-2-on.Place 1.19 g of (R, E) -3- (2 ', 5'-dimethylphenyl) -hex-4-enoic acid, 1.6 g of N-bromosuccinimide (NBS), 70 cm 3 in a round bottom flask. THF and a drop of acetic acid. The mixture was stirred on a magnetic stirrer at room temperature while monitoring the reaction by TLC hexane: acetone at a volume ratio of 3: 1. After complete reaction of the substrate whole is transferred to a separatory funnel, diluted with 30 cm 3 of diethyl ether and washed with saturated NaHCO3 (twice 20 cm 3 ). The organic layer is neutralized with brine against a indicator paper and dried with anhydrous magnesium sulfate. After the drying agent was filtered off, the solvent was evaporated. A crude mixture of bromolactones is obtained, which is isolated by column chromatography on silica gel using a hexane: acetone mixture by volume 20: 1 as eluent as one of the trans - (4S, 5R, 6S) -5- (1-bromoethyl) products. ) -4- (2 ', 5'-dimethylphenyl) -dihydrofuran-2-one in the amount of 0.174 g (11% of theory). The remaining reaction products are known isomers of the obtained compound, i.e. (4S, 5S, 6R) -5-1-bromo-4-r- (2 ', 5'-dimethylphenyl) -6-c-methyltetrahydropyran-2-one and cis - (4S, 5S, 6R) -5- (1-bromoethyl) -4- (2 ', 5'-dimethylphenyl) -dihydrofuran-2-one.
Dane fizyczne i spektroskopowe otrzymanego trans -(4S,5R,6S)-5-(1-bromoetylo)-4-(2',5'-dimetylofenylo)-dihydrofuran-2-onu są następujące:The physical and spectroscopic data of the obtained trans - (4S, 5R, 6S) -5- (1-bromoethyl) -4- (2 ', 5'-dimethylphenyl) -dihydrofuran-2-one are as follows:
Oleista ciecz, Rf = 0,38 (heksan/aceton, 3:1), [a]20 = - 3.8 (c 1,0; CH2CI2, ee = 99%).Oily liquid, Rf = 0.38 (hexane / acetone, 3: 1), [a] 20 = - 3.8 (c 1.0; CH2Cl2, ee = 99%).
1H NMR, δ 1,69 (d, J = 7,2 Hz, 3H, CH3-7), 2,34 (s, 3H, CH3-5'), 2,38 (s, 3H, CH3-2'), 2,54 (dd, J = 18,6 i 6,6 Hz, 1H, jeden z CH2-3), 3,14 (dd, J = 18,6 i 10,2 Hz, 1H, jeden z CH2-3), 3,95 (dublet dubletów dubletów, J = 10,2, 6,6 i 5,4 Hz, 1H, H-4), 4,33 (kwartet dubletów, J = 7,2 i 5,4 Hz, 1H, H-6), 4,67 (tryplet, J = 5,4 Hz, 1H, H-5), 7,01-7,03 (m, 2H, H-4', H-6'), 7,09 (d, J = 7,8 Hz, 1H, H-3');1H NMR, δ 1.69 (d, J = 7.2Hz, 3H, CH3-7), 2.34 (s, 3H, CH3-5 '), 2.38 (s, 3H, CH3-2' ), 2.54 (dd, J = 18.6 and 6.6 Hz, 1H, one CH2-3), 3.14 (dd, J = 18.6 and 10.2 Hz, 1H, one CH2 -3), 3.95 (doublet of doublets, J = 10.2, 6.6 and 5.4 Hz, 1H, H-4), 4.33 (quartet of doublets, J = 7.2 and 5.4 Hz, 1H, H-6), 4.67 (triplet, J = 5.4 Hz, 1H, H-5), 7.01-7.03 (m, 2H, H-4 ', H-6' ), 7.09 (d, J = 7.8Hz, 1H, H-3 ');
13C NMR, δ 19,45 (CH3-2'), 21,07 (CH3-5'), 23,37 (C-7), 38,41 (C-3), 38,53 (C-4), 45,29 (C-6), 86,76 (C5), 126,45 (C-6'), 128,47 (C-4'), 130,91 (C-3'), 133,29 (C-2'), 136,11 (C-5'), 136,42 (C-1), 176,41 (C-2); IR (cm-1): 1779 (s), 1505 (w), 1151 (s), 1006 (s), 811 (m), 634 (m). 13 C NMR, δ 19.45 (CH3-2 '), 21.07 (CH3-5'), 23.37 (C-7), 38.41 (C-3), 38.53 (C-4 ), 45.29 (C-6), 86.76 (C5), 126.45 (C-6 '), 128.47 (C-4'), 130.91 (C-3 '), 133, 29 (C-2 '), 136.11 (C-5'), 136.42 (C-1), 176.41 (C-2); IR (cm -1 ): 1779 (s), 1505 (w), 1151 (s), 1006 (s), 811 (m), 634 (m).
δ-Bromo-y-lakton z pierścieniem 2,5-dimetylofenylowym o wzorze 1 wykazuje aktywność antyproliferacyjną in vitro wobec psich linii komórek nowotworowych: chłoniaka B-komórkowego (CLBL-1), białaczki B-komórkowej (GL-1 oraz CLB70) oraz kostniakomięsaka (D17). Związek ten nie indukuje hemolizy erytrocytów, nie wpływa więc destrukcyjnie na błony erytrocytów. Badania oddziaływań związku z błonami biologicznymi wykazały natomiast, że powoduje on znaczące zmiany w obszarzeδ-Bromo-y-lactone with a 2,5-dimethylphenyl ring of formula 1 shows antiproliferative activity in vitro against canine tumor cell lines: B-cell lymphoma (CLBL-1), B-cell leukemia (GL-1 and CLB70) and osteosarcoma (D17). This compound does not induce erythrocyte haemolysis, so it does not have a destructive effect on erythrocyte membranes. Studies of the interaction of the relationship with biological membranes have shown that it causes significant changes in the area
PL 236 837 Β1 główek polarnych lipidów (wzrost uogólnionej polaryzacji sondy Laurdan oraz wzrost intensywności sondy MC540) i wykazuje nieznaczny wpływ na obszar hydrofobowy błon.PL 236 837 Β1 of the polar heads of lipids (increase in the generalized polarization of the Laurdan probe and increase in the intensity of the MC540 probe) and shows little effect on the hydrophobic region of the membranes.
Tabela 1 przedstawia wyniki testów biologicznych in vitro otrzymanego laktonu w stosunku do wybranych linii komórek nowotworowych. Testy przeprowadzono według metody opisanej w literaturze (Ferrari M., Fornasiero M.C., Isetta A.M. MTT colorimetric assay fortesting macrophage cytotoxic activity in vitro. Journal of immunological Methods, 1990, 131, 165-172).Table 1 shows the results of in vitro biological tests of the obtained lactone against selected tumor cell lines. The tests were performed according to the method described in the literature (Ferrari M., Fornasiero M.C., Isetta A.M. MTT colorimetric assay fortesting macrophage cytotoxic activity in vitro. Journal of immunological Methods, 1990, 131, 165-172).
Tabela 1.Table 1.
IC5o - stężenie związku, przy którym żywotność komórek wynosi 50% SEM - błąd standardowy średniejIC 5 o - concentration of the compound at which cell viability is 50% SEM - standard error of the mean
Claims (4)
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| PL426970A PL236837B1 (en) | 2018-09-10 | 2018-09-10 | trans-(4S,5R,6S)-5-(1-Bromoethyl)-4-(2',5'-dimethylphenyl)-dihydrofuran-2-one and method of its preparation |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| PL426970A PL236837B1 (en) | 2018-09-10 | 2018-09-10 | trans-(4S,5R,6S)-5-(1-Bromoethyl)-4-(2',5'-dimethylphenyl)-dihydrofuran-2-one and method of its preparation |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| PL426970A1 PL426970A1 (en) | 2020-03-23 |
| PL236837B1 true PL236837B1 (en) | 2021-02-22 |
Family
ID=69845699
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| PL426970A PL236837B1 (en) | 2018-09-10 | 2018-09-10 | trans-(4S,5R,6S)-5-(1-Bromoethyl)-4-(2',5'-dimethylphenyl)-dihydrofuran-2-one and method of its preparation |
Country Status (1)
| Country | Link |
|---|---|
| PL (1) | PL236837B1 (en) |
-
2018
- 2018-09-10 PL PL426970A patent/PL236837B1/en unknown
Also Published As
| Publication number | Publication date |
|---|---|
| PL426970A1 (en) | 2020-03-23 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| DE19726627A1 (en) | New intermediates for epothilone | |
| CN103601641A (en) | Glaucocalyxin derivatives and application thereof in preparation of antitumor drugs | |
| Araki et al. | Total synthesis and biological evaluation of oscillatoxins D, E, and F | |
| PL236838B1 (en) | trans-(4S,5R,6S)-5-(1-Bromoethyl)-4-(2',5'-dimethylphenyl)-dihydrofuran-2-one and method of its preparation | |
| Chen et al. | Synthesis and in vitro anticancer activity evaluation of novel bioreversible phosphate inositol derivatives | |
| Bachan et al. | Synthesis and anti-tumor activity of carbohydrate analogues of the tetrahydrofuran containing acetogenins | |
| Lochyński et al. | Lactones. Part 15: Synthesis of chiral spirolactones with a carane system—insect feeding deterrents | |
| CN105153030A (en) | Perfluoro group substituted isoquinoline-1,3(2H,4H)-diketone as well as preparation method and application thereof | |
| PL235029B1 (en) | (4R,5R,6S)-5-t-bromo-4-r-(2',5'-dimethylphenyl)-6-c-methyltetrahydropyran-2-one and method for obtaining it | |
| PL238121B1 (en) | Cis-(4S,5S,6R)-5-(1-bromethyl)-4-(2',5'-dimethylphenyl)-dihydrofuran-2-one and method for obtaining it | |
| PL235028B1 (en) | (4S,5S,6R)-5-t-bromo-4-r-(2',5'-dimethylphenyl)-6-c-methyltetrahydropyran-2-one and method for obtaining it | |
| PL238122B1 (en) | Cis-(4R,5R,6S)-5-(1-bromethyl)-4-(2',5'-dimethylphenyl)-dihydrofuran-2-one and method for obtaining it | |
| JP5894350B2 (en) | 2 ', 3'-dideoxy-5-fluorouridine derivatives, their production process and their use | |
| PL239567B1 (en) | (-)-rel-(1R, 6R,1'R) -1-(1'-Iodoethyl)-9-oxabicyclo[4.3.0]nonan-8-one and method of obtaining (-)-rel-(1R,6R,1'R)-1-(1'-iodoethyl)-9-oxabicyclo[4.3.0]nonan-8-one | |
| PL229559B1 (en) | Cis-(4S,5S,6R)-5-(1-iodoethane)-4-(2',5'-dimethylphenyl)dihydrofuran-2-one and trans-(4S,5R,6S)-5-(1-iodoethane)-4-(2',5'-dimethylphenyl)dihydrofuran-2-one and method for obtaining them simultaneously | |
| Zhang et al. | Design, synthesis, and preliminary evaluation of the biological activity of dithiocarbamate-3-epi-jaspine B hybrids | |
| PL229558B1 (en) | Cis-(4R,5R,6S)-5-(1-iodoethane)-4-(2',5'-dimethylphenyl)dihydrofuran-2-one and trans-(4S,5R,6S)-5-(1-iodoethane)-4-(2',5'-dimethylphenyl)dihydrofuran-2-one and method for obtaining them simultaneously | |
| PL238102B1 (en) | (+)-rel-(1R,6R,1'R)-1-(1'-Bromoethyl)-9-oxabicyclo[4.3.0]nonan-8-one and method of obtaining (+)-rel-(1R,6R,1'R)-1-(1'-bromoethyl)-9-oxabicyclo[4.3.0]nonan-8-one | |
| PL231188B1 (en) | Trans-(4S,5R,6S)-4-(benzo[d][1',3']-dioxol-5'-yl)-5-(1-iodoethyl)-dihydrofuran-2-one and method for obtaining it | |
| PL238079B1 (en) | (-)-rel-(1R,6R,1'R)-1-(1'-Bromoethyl)-9-oxabicyclo[4.3.0]nonan-8-one and method of obtaining (-)-rel-(1R,6R,1'R)-1-(1'-bromoethyl)-9-oxabicyclo[4.3.0]nonan-8-one | |
| PL231187B1 (en) | Trans-(4R,5S,6R)-4-(benzo[d][1',3']-dioxol-5'-yl)-5-(1-iodo-ethyl)-dihydrofuran and method for obtaining it | |
| PL238104B1 (en) | (+)-rel-(1R.6R, 1'R)-1-(1'-Chloroethyl)-9--oxabicyclo[4.3.0]nonan-8-one and method of obtaining (+)-rel-(1R .6R,1'R)-1-(1'-chloroethyl)-9-oxabicyclo[4.3.0]nonan-8-one | |
| CN109096332A (en) | A kind of chlorinated triphenyl base -4-(trifluoromethyl Benzamido) fourth base Phosphonium synthetic method and its application in anti-tumor drug | |
| PL221300B1 (en) | Cis- (4S, 5S, 6R) -5- (1-iodoethyl) -4- (4'-isopropylphenyl) dihydrofuran-2-one and trans- (4S, 5R, 6S) -5- (1-iodoethyl) -4- (4'-isopropylphenyl) dihydrofuran-2-one and the method of their simultaneous preparation | |
| PL238101B1 (en) | (+)-rel-(1R,6R,1'R)-1-(1'-Iodoethyl)-9-oxabicyclo[4.3.0]nonan-8-one and method of obtaining (+)-rel-(1R,6R, 1'R)-1-(1'-iodoethyl)-9-oxabicyclo[4.3.0]nonan-8-one |