PL246770B1 - 2'-Hydroxy-2-hydroxymethyl-3'-O-β-D-(4''-O-methylglucopyranosyl)-dihydrochalcone and method for the preparation of 2'-hydroxy-2-hydroxymethyl-3'-O-β-D- (4''-O-methylglucopyranosyl)-dihydrochalcone - Google Patents
2'-Hydroxy-2-hydroxymethyl-3'-O-β-D-(4''-O-methylglucopyranosyl)-dihydrochalcone and method for the preparation of 2'-hydroxy-2-hydroxymethyl-3'-O-β-D- (4''-O-methylglucopyranosyl)-dihydrochalcone Download PDFInfo
- Publication number
- PL246770B1 PL246770B1 PL438353A PL43835321A PL246770B1 PL 246770 B1 PL246770 B1 PL 246770B1 PL 438353 A PL438353 A PL 438353A PL 43835321 A PL43835321 A PL 43835321A PL 246770 B1 PL246770 B1 PL 246770B1
- Authority
- PL
- Poland
- Prior art keywords
- hydroxy
- dihydrochalcone
- methylglucopyranosyl
- hydroxymethyl
- carried out
- Prior art date
Links
- 238000000034 method Methods 0.000 title claims description 10
- 238000002360 preparation method Methods 0.000 title description 2
- 230000009466 transformation Effects 0.000 claims abstract description 8
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 8
- 239000003960 organic solvent Substances 0.000 claims abstract description 7
- 239000000758 substrate Substances 0.000 claims abstract description 7
- 241000751139 Beauveria bassiana Species 0.000 claims abstract description 6
- ARUMOQJPOFYOBO-UHFFFAOYSA-N 1-(2-hydroxyphenyl)-3-(2-methylphenyl)prop-2-en-1-one Chemical compound CC1=CC=CC=C1C=CC(=O)C1=CC=CC=C1O ARUMOQJPOFYOBO-UHFFFAOYSA-N 0.000 claims abstract description 4
- 238000004519 manufacturing process Methods 0.000 claims abstract description 4
- 241000233866 Fungi Species 0.000 claims abstract description 3
- 239000007795 chemical reaction product Substances 0.000 claims abstract 2
- 239000000047 product Substances 0.000 claims abstract 2
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 9
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 claims description 6
- 238000004237 preparative chromatography Methods 0.000 claims description 2
- 230000008569 process Effects 0.000 claims description 2
- 238000000746 purification Methods 0.000 claims description 2
- PXLWOFBAEVGBOA-UHFFFAOYSA-N dihydrochalcone Natural products OC1C(O)C(O)C(CO)OC1C1=C(O)C=CC(C(=O)CC(O)C=2C=CC(O)=CC=2)=C1O PXLWOFBAEVGBOA-UHFFFAOYSA-N 0.000 abstract description 9
- QGGZBXOADPVUPN-UHFFFAOYSA-N dihydrochalcone Chemical compound C=1C=CC=CC=1C(=O)CCC1=CC=CC=C1 QGGZBXOADPVUPN-UHFFFAOYSA-N 0.000 abstract description 9
- 150000002215 flavonoids Chemical class 0.000 description 9
- 229930003935 flavonoid Natural products 0.000 description 8
- 235000017173 flavonoids Nutrition 0.000 description 8
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 6
- 150000001875 compounds Chemical class 0.000 description 6
- REFJWTPEDVJJIY-UHFFFAOYSA-N Quercetin Chemical group C=1C(O)=CC(O)=C(C(C=2O)=O)C=1OC=2C1=CC=C(O)C(O)=C1 REFJWTPEDVJJIY-UHFFFAOYSA-N 0.000 description 5
- 238000010521 absorption reaction Methods 0.000 description 5
- 235000003599 food sweetener Nutrition 0.000 description 5
- 235000013305 food Nutrition 0.000 description 4
- VGEREEWJJVICBM-UHFFFAOYSA-N phloretin Chemical compound C1=CC(O)=CC=C1CCC(=O)C1=C(O)C=C(O)C=C1O VGEREEWJJVICBM-UHFFFAOYSA-N 0.000 description 4
- 244000222996 Syzygium nervosum Species 0.000 description 3
- 230000003078 antioxidant effect Effects 0.000 description 3
- 230000036983 biotransformation Effects 0.000 description 3
- 244000005700 microbiome Species 0.000 description 3
- 210000000813 small intestine Anatomy 0.000 description 3
- 235000000346 sugar Nutrition 0.000 description 3
- 239000003765 sweetening agent Substances 0.000 description 3
- ZWTDXYUDJYDHJR-UHFFFAOYSA-N (E)-1-(2,4-dihydroxyphenyl)-3-(2,4-dihydroxyphenyl)-2-propen-1-one Natural products OC1=CC(O)=CC=C1C=CC(=O)C1=CC=C(O)C=C1O ZWTDXYUDJYDHJR-UHFFFAOYSA-N 0.000 description 2
- DQFBYFPFKXHELB-UHFFFAOYSA-N Chalcone Natural products C=1C=CC=CC=1C(=O)C=CC1=CC=CC=C1 DQFBYFPFKXHELB-UHFFFAOYSA-N 0.000 description 2
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 2
- 241000196324 Embryophyta Species 0.000 description 2
- 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 2
- 241000699660 Mus musculus Species 0.000 description 2
- YQHMWTPYORBCMF-UHFFFAOYSA-N Naringenin chalcone Natural products C1=CC(O)=CC=C1C=CC(=O)C1=C(O)C=C(O)C=C1O YQHMWTPYORBCMF-UHFFFAOYSA-N 0.000 description 2
- 102000005348 Neuraminidase Human genes 0.000 description 2
- 108010006232 Neuraminidase Proteins 0.000 description 2
- IOUVKUPGCMBWBT-DARKYYSBSA-N Phloridzin Natural products O[C@H]1[C@@H](O)[C@H](O)[C@H](CO)O[C@H]1OC1=CC(O)=CC(O)=C1C(=O)CCC1=CC=C(O)C=C1 IOUVKUPGCMBWBT-DARKYYSBSA-N 0.000 description 2
- ZVOLCUVKHLEPEV-UHFFFAOYSA-N Quercetagetin Natural products C1=C(O)C(O)=CC=C1C1=C(O)C(=O)C2=C(O)C(O)=C(O)C=C2O1 ZVOLCUVKHLEPEV-UHFFFAOYSA-N 0.000 description 2
- HWTZYBCRDDUBJY-UHFFFAOYSA-N Rhynchosin Natural products C1=C(O)C(O)=CC=C1C1=C(O)C(=O)C2=CC(O)=C(O)C=C2O1 HWTZYBCRDDUBJY-UHFFFAOYSA-N 0.000 description 2
- 230000009471 action Effects 0.000 description 2
- 230000001093 anti-cancer Effects 0.000 description 2
- -1 anti-inflammatory Substances 0.000 description 2
- 239000003963 antioxidant agent Substances 0.000 description 2
- 235000006708 antioxidants Nutrition 0.000 description 2
- 210000004027 cell Anatomy 0.000 description 2
- 235000005513 chalcones Nutrition 0.000 description 2
- 150000001789 chalcones Chemical class 0.000 description 2
- 230000007278 cognition impairment Effects 0.000 description 2
- 239000002537 cosmetic Substances 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 230000002255 enzymatic effect Effects 0.000 description 2
- 238000000605 extraction Methods 0.000 description 2
- 235000019264 food flavour enhancer Nutrition 0.000 description 2
- 239000008103 glucose Substances 0.000 description 2
- 229930182470 glycoside Natural products 0.000 description 2
- 150000002338 glycosides Chemical class 0.000 description 2
- 230000033444 hydroxylation Effects 0.000 description 2
- 238000005805 hydroxylation reaction Methods 0.000 description 2
- MWDZOUNAPSSOEL-UHFFFAOYSA-N kaempferol Natural products OC1=C(C(=O)c2cc(O)cc(O)c2O1)c3ccc(O)cc3 MWDZOUNAPSSOEL-UHFFFAOYSA-N 0.000 description 2
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 2
- 239000000203 mixture Substances 0.000 description 2
- 235000010434 neohesperidine DC Nutrition 0.000 description 2
- IOUVKUPGCMBWBT-UHFFFAOYSA-N phloridzosid Natural products OC1C(O)C(O)C(CO)OC1OC1=CC(O)=CC(O)=C1C(=O)CCC1=CC=C(O)C=C1 IOUVKUPGCMBWBT-UHFFFAOYSA-N 0.000 description 2
- 235000019139 phlorizin Nutrition 0.000 description 2
- IOUVKUPGCMBWBT-QNDFHXLGSA-N phlorizin Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@H]1OC1=CC(O)=CC(O)=C1C(=O)CCC1=CC=C(O)C=C1 IOUVKUPGCMBWBT-QNDFHXLGSA-N 0.000 description 2
- 229960001285 quercetin Drugs 0.000 description 2
- 235000005875 quercetin Nutrition 0.000 description 2
- 238000000844 transformation Methods 0.000 description 2
- 238000011830 transgenic mouse model Methods 0.000 description 2
- HTDSMOBGCNRBHQ-RMKNXTFCSA-N (E)-4,2',4'-trihydroxy-6'-methoxy-3',5'-dimethylchalcone Chemical compound COC1=C(C)C(O)=C(C)C(O)=C1C(=O)\C=C\C1=CC=C(O)C=C1 HTDSMOBGCNRBHQ-RMKNXTFCSA-N 0.000 description 1
- HTDSMOBGCNRBHQ-UHFFFAOYSA-N (E)-4,2',4'-trihydroxy-6'-methoxy-3',5'-dimethylchalcone Natural products COC1=C(C)C(O)=C(C)C(O)=C1C(=O)C=CC1=CC=C(O)C=C1 HTDSMOBGCNRBHQ-UHFFFAOYSA-N 0.000 description 1
- JUZVHLGKYJTCKP-CMDGGOBGSA-N 2',4'-dihydroxy-3'-methyl-6'-methoxychalcone Chemical compound COC1=CC(O)=C(C)C(O)=C1C(=O)\C=C\C1=CC=CC=C1 JUZVHLGKYJTCKP-CMDGGOBGSA-N 0.000 description 1
- TZEQDSMFACWASC-MDZDMXLPSA-N 2',4'-dihydroxy-6'-methoxy-3',5'-dimethylchalcone Chemical compound COC1=C(C)C(O)=C(C)C(O)=C1C(=O)\C=C\C1=CC=CC=C1 TZEQDSMFACWASC-MDZDMXLPSA-N 0.000 description 1
- SPWBEELZNSXNME-CMDGGOBGSA-N 2,2',4'-trihydroxy-6'-methoxy-3',5'-dimethylchalcone Chemical compound COC1=C(C)C(O)=C(C)C(O)=C1C(=O)\C=C\C1=CC=CC=C1O SPWBEELZNSXNME-CMDGGOBGSA-N 0.000 description 1
- ZWTRSTWJBWJEFR-UHFFFAOYSA-N 3-(2-methoxyphenyl)-1-phenyl-2-propen-1-one Chemical compound COC1=CC=CC=C1C=CC(=O)C1=CC=CC=C1 ZWTRSTWJBWJEFR-UHFFFAOYSA-N 0.000 description 1
- DFPMSGMNTNDNHN-JJLSSNRUSA-N 7-[(2s,3r,4s,5s,6r)-4,5-dihydroxy-6-(hydroxymethyl)-3-[(2s,3r,4r,5r,6s)-3,4,5-trihydroxy-6-methyloxan-2-yl]oxyoxan-2-yl]oxy-5-hydroxy-2-(4-hydroxyphenyl)-2,3-dihydrochromen-4-one Chemical compound O[C@@H]1[C@H](O)[C@@H](O)[C@H](C)O[C@H]1O[C@H]1[C@H](OC=2C=C3OC(CC(=O)C3=C(O)C=2)C=2C=CC(O)=CC=2)O[C@H](CO)[C@@H](O)[C@@H]1O DFPMSGMNTNDNHN-JJLSSNRUSA-N 0.000 description 1
- 238000010175 APPswe/PSEN1dE9 Methods 0.000 description 1
- TWCMVXMQHSVIOJ-UHFFFAOYSA-N Aglycone of yadanzioside D Natural products COC(=O)C12OCC34C(CC5C(=CC(O)C(O)C5(C)C3C(O)C1O)C)OC(=O)C(OC(=O)C)C24 TWCMVXMQHSVIOJ-UHFFFAOYSA-N 0.000 description 1
- 208000024827 Alzheimer disease Diseases 0.000 description 1
- PLMKQQMDOMTZGG-UHFFFAOYSA-N Astrantiagenin E-methylester Natural products CC12CCC(O)C(C)(CO)C1CCC1(C)C2CC=C2C3CC(C)(C)CCC3(C(=O)OC)CCC21C PLMKQQMDOMTZGG-UHFFFAOYSA-N 0.000 description 1
- 241000223679 Beauveria Species 0.000 description 1
- 239000004321 EU approved sweetener Substances 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- 239000001329 FEMA 3811 Substances 0.000 description 1
- 239000001183 FEMA 4495 Substances 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
- 244000141359 Malus pumila Species 0.000 description 1
- CWBZAESOUBENAP-QVNVHUMTSA-N Naringin dihydrochalcone Chemical compound O[C@@H]1[C@H](O)[C@@H](O)[C@H](C)O[C@H]1O[C@H]1[C@H](OC=2C=C(O)C(C(=O)CCC=3C=CC(O)=CC=3)=C(O)C=2)O[C@H](CO)[C@@H](O)[C@@H]1O CWBZAESOUBENAP-QVNVHUMTSA-N 0.000 description 1
- 241000700605 Viruses Species 0.000 description 1
- 241000235015 Yarrowia lipolytica Species 0.000 description 1
- 230000032683 aging Effects 0.000 description 1
- 238000010171 animal model Methods 0.000 description 1
- 230000003178 anti-diabetic effect Effects 0.000 description 1
- 230000003110 anti-inflammatory effect Effects 0.000 description 1
- 239000003472 antidiabetic agent Substances 0.000 description 1
- 239000004599 antimicrobial Substances 0.000 description 1
- 235000021016 apples Nutrition 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- 210000000941 bile Anatomy 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 230000033228 biological regulation Effects 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 230000003293 cardioprotective effect Effects 0.000 description 1
- 230000015556 catabolic process Effects 0.000 description 1
- 239000003054 catalyst Substances 0.000 description 1
- 238000006555 catalytic reaction Methods 0.000 description 1
- 150000001765 catechin Chemical class 0.000 description 1
- ADRVNXBAWSRFAJ-UHFFFAOYSA-N catechin Natural products OC1Cc2cc(O)cc(O)c2OC1c3ccc(O)c(O)c3 ADRVNXBAWSRFAJ-UHFFFAOYSA-N 0.000 description 1
- 235000005487 catechin Nutrition 0.000 description 1
- 210000000170 cell membrane Anatomy 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- CXQWRCVTCMQVQX-UHFFFAOYSA-N cis-dihydroquercetin Natural products O1C2=CC(O)=CC(O)=C2C(=O)C(O)C1C1=CC=C(O)C(O)=C1 CXQWRCVTCMQVQX-UHFFFAOYSA-N 0.000 description 1
- 235000020971 citrus fruits Nutrition 0.000 description 1
- 238000006731 degradation reaction Methods 0.000 description 1
- FMGSKLZLMKYGDP-USOAJAOKSA-N dehydroepiandrosterone Chemical compound C1[C@@H](O)CC[C@]2(C)[C@H]3CC[C@](C)(C(CC4)=O)[C@@H]4[C@@H]3CC=C21 FMGSKLZLMKYGDP-USOAJAOKSA-N 0.000 description 1
- 235000005911 diet Nutrition 0.000 description 1
- 230000000378 dietary effect Effects 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 238000009826 distribution Methods 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 239000003480 eluent Substances 0.000 description 1
- 229930182486 flavonoid glycoside Natural products 0.000 description 1
- 150000007955 flavonoid glycosides Chemical class 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 229930182478 glucoside Natural products 0.000 description 1
- 150000008131 glucosides Chemical class 0.000 description 1
- 230000013595 glycosylation Effects 0.000 description 1
- 238000006206 glycosylation reaction Methods 0.000 description 1
- 238000004128 high performance liquid chromatography Methods 0.000 description 1
- PFOARMALXZGCHY-UHFFFAOYSA-N homoegonol Natural products C1=C(OC)C(OC)=CC=C1C1=CC2=CC(CCCO)=CC(OC)=C2O1 PFOARMALXZGCHY-UHFFFAOYSA-N 0.000 description 1
- 244000052637 human pathogen Species 0.000 description 1
- 238000005984 hydrogenation reaction Methods 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 208000037801 influenza A (H1N1) Diseases 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 230000004060 metabolic process Effects 0.000 description 1
- 230000000813 microbial effect Effects 0.000 description 1
- 230000002906 microbiologic effect Effects 0.000 description 1
- 229930014626 natural product Natural products 0.000 description 1
- 229940089953 neohesperidin dihydrochalcone Drugs 0.000 description 1
- 239000000879 neohesperidine DC Substances 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 238000000425 proton nuclear magnetic resonance spectrum Methods 0.000 description 1
- FDRQPMVGJOQVTL-UHFFFAOYSA-N quercetin rutinoside Natural products OC1C(O)C(O)C(CO)OC1OCC1C(O)C(O)C(O)C(OC=2C(C3=C(O)C=C(O)C=C3OC=2C=2C=C(O)C(O)=CC=2)=O)O1 FDRQPMVGJOQVTL-UHFFFAOYSA-N 0.000 description 1
- 150000003254 radicals Chemical class 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- IKGXIBQEEMLURG-BKUODXTLSA-N rutin Chemical compound O[C@H]1[C@H](O)[C@@H](O)[C@H](C)O[C@@H]1OC[C@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](OC=2C(C3=C(O)C=C(O)C=C3OC=2C=2C=C(O)C(O)=CC=2)=O)O1 IKGXIBQEEMLURG-BKUODXTLSA-N 0.000 description 1
- 229960004555 rutoside Drugs 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 230000003595 spectral effect Effects 0.000 description 1
- 125000001424 substituent group Chemical group 0.000 description 1
- 150000008163 sugars Chemical class 0.000 description 1
- 235000019605 sweet taste sensations Nutrition 0.000 description 1
- 201000010740 swine influenza Diseases 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 229940124597 therapeutic agent Drugs 0.000 description 1
- 241000712461 unidentified influenza virus Species 0.000 description 1
- 150000008136 β-glycosides Chemical class 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12P—FERMENTATION OR ENZYME-USING PROCESSES TO SYNTHESISE A DESIRED CHEMICAL COMPOUND OR COMPOSITION OR TO SEPARATE OPTICAL ISOMERS FROM A RACEMIC MIXTURE
- C12P19/00—Preparation of compounds containing saccharide radicals
- C12P19/44—Preparation of O-glycosides, e.g. glucosides
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H15/00—Compounds containing hydrocarbon or substituted hydrocarbon radicals directly attached to hetero atoms of saccharide radicals
- C07H15/20—Carbocyclic rings
- C07H15/203—Monocyclic carbocyclic rings other than cyclohexane rings; Bicyclic carbocyclic ring systems
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12R—INDEXING SCHEME ASSOCIATED WITH SUBCLASSES C12C - C12Q, RELATING TO MICROORGANISMS
- C12R2001/00—Microorganisms ; Processes using microorganisms
- C12R2001/645—Fungi ; Processes using fungi
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Engineering & Computer Science (AREA)
- Wood Science & Technology (AREA)
- Biochemistry (AREA)
- Biotechnology (AREA)
- General Health & Medical Sciences (AREA)
- Genetics & Genomics (AREA)
- Health & Medical Sciences (AREA)
- Zoology (AREA)
- Molecular Biology (AREA)
- Microbiology (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Bioinformatics & Cheminformatics (AREA)
- General Engineering & Computer Science (AREA)
- Saccharide Compounds (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
Abstract
Przedmiotem zgłoszenia jest 2'-hydroksy-2-hydroksymetylo-3'-O-β-D-(4"-O-metyloglukopiranozylo)dihydrochalkon o wzorze 2 oraz sposób wytwarzania 2'-hydroksy-2-hydroksymetylo-3'-O-β-D-(4"-O-metyloglukopiranozylo)-dihydrochalkonu polegający na tym, że do podłoża odpowiedniego dla grzybów strzępkowych wprowadza się szczep Beauveria bassiana KCH J1.5, następnie po upływie co najmniej 72 godzin do hodowli wprowadza się substrat, którym jest 2'-hydroksy-2-metylochalkon o wzorze 1, rozpuszczony w rozpuszczalniku organicznym mieszającym się z wodą, transformację prowadzi się w temperaturze od 20 do 30 stopni Celsjusza, przy ciągłym wstrząsaniu, co najmniej 96 godzin, po czym produkt ekstrahuje się rozpuszczalnikiem organicznym niemieszającym się z wodą i oczyszcza chromatograficznie, przy czym produkt reakcji jakim jest 2'-hydroksy-2-hydroksymetylo-3'-O-β-D-(4"-O-metyloglukopiranozylo)-dihydrochalkon o wzorze 2 znajduje się we frakcji o pośredniej polarności, w drugim paśmie od linii startu.The subject of the application is 2'-hydroxy-2-hydroxymethyl-3'-O-β-D-(4"-O-methylglucopyranosyl)dihydrochalcone of formula 2 and a method for producing 2'-hydroxy-2-hydroxymethyl-3'-O-β-D-(4"-O-methylglucopyranosyl)dihydrochalcone, which comprises introducing Beauveria bassiana KCH J1.5 strain into a medium suitable for filamentous fungi, then after at least 72 hours a substrate is introduced into the culture, which is 2'-hydroxy-2-methylchalcone of formula 1, dissolved in an organic solvent miscible with water, the transformation is carried out at a temperature of 20 to 30 degrees Celsius, with continuous shaking, for at least 96 hours, after which the product is extracted with an organic solvent immiscible with water and purified chromatographically, wherein the reaction product, which is 2'-Hydroxy-2-hydroxymethyl-3'-O-β-D-(4"-O-methylglucopyranosyl)dihydrochalcone of formula 2 is located in the fraction of intermediate polarity, in the second band from the starting line.
Description
Opis wynalazkuDescription of the invention
Przedmiotem wynalazku jest sposób wytwarzania 2’-hydroksy-2-hydroksymetylo-3’-O-/>-D-(4::-O -metyloglukopiranozylo)-dihydrochalkonu.The subject of the invention is a method for preparing 2'-hydroxy-2-hydroxymethyl-3'-O-/>-D-(4 :: -O-methylglucopyranosyl)dihydrochalcone.
Wynalazek może znaleźć zastosowanie do wytwarzania związku przeciwutleniającego, przeciwdrobnoustrojowego, substancji wzmacniającej smak i potencjalnego słodzika w preparatach farmaceutycznych, produktach spożywczych oraz formulacjach kosmetycznych.The invention may find application in the production of an antioxidant, antimicrobial compound, a flavor enhancer and a potential sweetener in pharmaceutical preparations, food products and cosmetic formulations.
Naturalne flawonoidy z jedną lub kilkoma grupami metylowymi występują w roślinach sporadycznie. Z azjatyckiego drzewa Syzygium nervosum (Cleistocalyx operculatus) izolowano C- i O-metylowane chalkony: (E)-4,2’,4’-trihydroksy-6’-metoksy-3’,5’-dimetylochalkon, (E)-2’,4’-dihydroksy-6’-metoksy-3’,5’-dimetylochalkon, (E)-2’,4’-dihydroksy-6’-metoksy-3’-metylochalkon, (E)-2,2’,4’-trihydroksy-6’-metoksy-3’,5’-dimetylochalkon. Związki te wykazywały silną inhibicję wobec enzymów pochodzących od dwóch szczepów wirusa grypy: H1N1 oraz H9N2. Blokowały one działanie neuraminidaz, umożliwiających wirusom opuszczanie zakażonych komórek poprzez rozkład ich błon komórkowych (Dao T. T., Tung B. T., Nguyen P. H., Thuong P. T., Yoo S. S., Kim E. H., Kim S. K., Oh W. K. C-methylated flavonoids form Cleistocalyx operculatus and their inhibitory effects on novel influenza A (H1N1) neuraminidase. Journal of Natural Products 2010, 73, 1636-1642).Natural flavonoids with one or more methyl groups occur sporadically in plants. From the Asian tree Syzygium nervosum (Cleistocalyx operculatus), C- and O-methylated chalcones were isolated: (E)-4,2',4'-trihydroxy-6'-methoxy-3',5'-dimethylchalcone, (E)-2',4'-dihydroxy-6'-methoxy-3',5'-dimethylchalcone, (E)-2',4'-dihydroxy-6'-methoxy-3'-methylchalcone, (E)-2,2',4'-trihydroxy-6'-methoxy-3',5'-dimethylchalcone. These compounds showed strong inhibition of enzymes derived from two strains of influenza virus: H1N1 and H9N2. They blocked the action of neuraminidases, which enable viruses to leave infected cells by breaking down their cell membranes (Dao T. T., Tung B. T., Nguyen P. H., Thuong P. T., Yoo S. S., Kim E. H., Kim S. K., Oh W. K. C-methylated flavonoids form Cleistocalyx operculatus and their inhibitory effects on novel influenza A (H1N1) neuraminidase. Journal of Natural Products 2010, 73, 1636-1642).
Naturalne dihydrochalkony floretyna i jej glikozyd florydzyna, które występują w skórce i miąższu jabłka, wykazują licznie udokumentowane właściwości prozdrowotne: antyoksydacyjną, przeciwzapalną, przeciwcukrzycową, przeciwnowotworową i kardioprotekcyjną (Choi Y. Biochemical basis of anti-cancer-effects of phloretin - a natural dihydrochalcone. Molecules 2018, 24, 278; Tian L., Cao J., Zhao T., Liu Y., Khan A., Cheng G. The bioavailability, extraction, biosynthesis and distribution of natural dihydrochalcone: phloridzin. International Journal of Molecular Sciences 2021,22, 962).Natural dihydrochalcones phloretin and its glycoside phloridzin, which occur in the skin and flesh of apples, have numerous documented health-promoting properties: antioxidant, anti-inflammatory, antidiabetic, anticancer and cardioprotective (Choi Y. Biochemical basis of anti-cancer-effects of phloretin - a natural dihydrochalcone. Molecules 2018, 24, 278; Tian L., Cao J., Zhao T., Liu Y., Khan A., Cheng G. The bioavailability, extraction, biosynthesis and distribution of natural dihydrochalcone: phloridzin. International Journal of Molecular Sciences 2021,22, 962).
W badaniach nad dihydrochalkonem naringiny z udziałem transgenicznych myszy jako modeli zwierzęcych choroby Alzheimera, zaobserwowano efekt złagodzenia deficytów poznawczych, co stwarza możliwość zastosowania tego związku jako środka leczniczego (Yang W., Zhou K., Zhou Y., An Y., Hu T., Lu J., Huang S., Pei G. Narindin dihydrochalcone ameliorates cognitive deficits and neuropatholody in APP/PS1 Transgenic Mice. Frontiers in Aging Neuroscience 2018, 10, 169).In studies on naringin dihydrochalcone using transgenic mice as animal models of Alzheimer's disease, the effect of alleviating cognitive deficits was observed, which creates the possibility of using this compound as a therapeutic agent (Yang W., Zhou K., Zhou Y., An Y., Hu T., Lu J., Huang S., Pei G. Narindin dihydrochalcone ameliorates cognitive deficits and neuropatholody in APP/PS1 Transgenic Mice. Frontiers in Aging Neuroscience 2018, 10, 169).
Dihydrochalkony wykazują słodki smak i mogą znaleźć zastosowanie jako prozdrowotne słodziki (Janeczko T., Gładkowski W., Kostrzewa-Susłow E. Microbial transformations of chalcones to produce food sweetener derivatives. Journal of Molecular Catalysis B: Enzymatic 2013, 98, 55-61; Łużny M., Kozłowska E., Kostrzewa-Susłow E., Janeczko T. Highly efective, regiospecific hydrogenation of methoxychalcone by Yarrowia lipolytica enables production of food sweeteners. Catalysts 2020, 10, 1135). Najlepiej poznany i zbadany dihydrochalkon pozyskiwany ze skórek owoców cytrusowych - dihydrochalkon neohesperydyny (E-959) został dopuszczony do stosowania jako słodzik i substancja wzmacniająca smak, a jego zastosowanie reguluje Rozporządzenie Komisji Europejskiej nr 1129/2011 z 11 listopada 2011 r.Dihydrochalcones have a sweet taste and can be used as health-promoting sweeteners (Janeczko T., Gładkowski W., Kostrzewa-Susłow E. Microbial transformations of chalcones to produce food sweetener derivatives. Journal of Molecular Catalysis B: Enzymatic 2013, 98, 55-61; Łużny M., Kozłowska E., Kostrzewa-Susłow E., Janeczko T. Highly effective, regiospecific hydrogenation of methoxychalcone by Yarrowia lipolytica enables production of food sweeteners. Catalysts 2020, 10, 1135). The best known and studied dihydrochalcone obtained from citrus fruit peels - neohesperidin dihydrochalcone (E-959) has been approved for use as a sweetener and flavour enhancer, and its use is regulated by European Commission Regulation No. 1129/2011 of 11 November 2011.
Większość flawonoidów, poza katechinami, jest obecna w roślinach w połączeniu z cukrami, jako ^-glikozydy. Glikozylacja skutkuje: wzrostem rozpuszczalności w wodzie i stabilności cząsteczki flawonoidu oraz przyswajalności przyjmowanych z pokarmem związków flawonoidowych. Zasadniczo glukozydy są jedynymi glikozydami, które mogą być absorbowane w jelicie cienkim. Natomiast flawonoidy niezaabsorbowane w jelicie cienkim oraz zaabsorbowane flawonoidy wydzielone z żółcią ulegają degradacji wraz z rozerwaniem struktury pierścieniowej przez mikroorganizmy (Hollman, P. C. Absorption, bioavailability, and metabolism of flavonoids. Pharmaceutical Biology, 2004, 42, 74-83; Plaza, M.; Pozzo, T.; Liu, J.; Gulshan Ara, K. Z.; Turner, C.; Nordberg Karlsson, E. Substituent effects on in vitro antioxidizing properties, stability, and solubility in flavonoids. Journal of Agricultural Food Chemistry, 2014, 62, 3321-3333).Most flavonoids, except catechins, are present in plants in combination with sugars, as β-glycosides. Glycosylation results in: increased water solubility and stability of the flavonoid molecule and the absorption of flavonoid compounds taken with food. In general, glucosides are the only glycosides that can be absorbed in the small intestine. In contrast, flavonoids not absorbed in the small intestine and absorbed flavonoids secreted with bile undergo degradation with the disruption of the ring structure by microorganisms (Hollman, P. C. Absorption, bioavailability, and metabolism of flavonoids. Pharmaceutical Biology, 2004, 42, 74-83; Plaza, M.; Pozzo, T.; Liu, J.; Gulshan Ara, K. Z.; Turner, C.; Nordberg Karlsson, E. Substituent effects on in vitro antioxidant properties, stability, and solubility in flavonoids. Journal of Agricultural Food Chemistry, 2014, 62, 3321-3333).
Hollman i in., wykazali, że cząsteczka glukozy przyłączona w pozycji 3 kwercetyny (3,3’,4’,5,7-pentahydroksyflawon) zwiększa absorpcję tego związku w jelicie cienkim do 52%, w porównaniu z 24% absorpcją aglikonu kwercetyny i 17% rutynozydu kwercetyny (Hollman, P. C.; Bijsman, M. N. C. P.; van Gameren, Y.; Cnossen, E. P. J.; de Vries, J. H.; Katan, M. B. The sugar moiety is a major determinant of the absorption of dietary flavonoid glycosides in man. Free Radical Research, 1999, 31,569-573).Hollman et al., showed that a glucose molecule attached at the 3-position of quercetin (3,3',4',5,7-pentahydroxyflavone) increases the absorption of this compound in the small intestine to 52%, compared with 24% absorption for quercetin aglycone and 17% for quercetin rutinoside (Hollman, P. C.; Bijsman, M. N. C. P.; van Gameren, Y.; Cnossen, E. P. J.; de Vries, J. H.; Katan, M. B. The sugar moiety is a major determinant of the absorption of dietary flavonoid glycosides in man. Free Radical Research, 1999, 31, 569-573).
Znany jest szczep Beauveria bassiana KCH J1.5 ujawniony w literaturze (Kozłowska E., Urbaniak M., Hoc N., Grzeszczuk J., Dymarska M., Stępień Ł., Pląskowska E., Kostrzewa-Susłow E., Janeczko T. Cascade biotransformation of dehydroepiandrosterone (DHEA) by Beauveria species. Scientific Reports, 2018, 8: 13449).The Beauveria bassiana KCH J1.5 strain is known and has been disclosed in the literature (Kozłowska E., Urbaniak M., Hoc N., Grzeszczuk J., Dymarska M., Stępień Ł., Pląskowska E., Kostrzewa-Susłow E., Janeczko T. Cascade biotransformation of dehydroepiandrosterone (DHEA) by Beauveria species. Scientific Reports, 2018, 8: 13449).
W ostatnich latach, w leczeniu różnych chorób i ich zapobieganiu, coraz większe znaczenie zyskują związki pochodzenia naturalnego oraz ich odpowiedniki uznawane za naturalne, które uzyskano na drodze przekształceń mikrobiologicznych. Dlatego istotne jest opracowywanie nowych metod wytwarzania związków aktywnych biologicznie na drodze biotransformacji, użytecznych dla przemysłu farmaceutycznego, kosmetycznego i spożywczego.In recent years, in the treatment and prevention of various diseases, compounds of natural origin and their equivalents considered natural, which were obtained through microbiological transformations, have become increasingly important. Therefore, it is important to develop new methods of producing biologically active compounds through biotransformation, useful for the pharmaceutical, cosmetic and food industries.
W dostępnej literaturze brak jest informacji na temat otrzymywania 2’-hydroksy-2-hydroksymetylo-3’-O-/>-D-(4::-O-metyloglukopiranozylo)-dihydrochalkonu.There is no information in the available literature on the preparation of 2'-hydroxy-2-hydroxymethyl-3'-O-/>-D-(4 :: -O-methylglucopyranosyl)-dihydrochalcone.
Istota sposobu według wynalazku polega na tym, że do podłoża odpowiedniego dla grzybów strzępkowych wprowadza się szczep Beauveria bassiana KCH J1.5. Po upływie co najmniej 72 godzin do hodowli wprowadza się substrat, którym jest 2’-hydroksy-2-metylochalkon, rozpuszczony w rozpuszczalniku organicznym mieszającym się z wodą. Transformację prowadzi się w temperaturze od 20 do 30 stopni Celsjusza, przy ciągłym wstrząsaniu, przez co najmniej 96 godzin. Następnie produkt ekstrahuje się rozpuszczalnikiem organicznym niemieszającym się z wodą oraz oczyszcza chromatograficznie. 2’-Hydroksy-2-hydroksymetylo-3’-O-^-D-(4”- O- metyloglukopiranozylo)-dihydrochalkon znajduje się we frakcji o pośredniej polarności, w drugim paśmie od linii startu.The essence of the method according to the invention consists in introducing the Beauveria bassiana KCH J1.5 strain into a medium suitable for filamentous fungi. After at least 72 hours, the substrate, which is 2'-hydroxy-2-methylchalcone, dissolved in an organic solvent miscible with water, is introduced into the culture. The transformation is carried out at a temperature of 20 to 30 degrees Celsius, with continuous shaking, for at least 96 hours. Then the product is extracted with an organic solvent immiscible with water and purified chromatographically. 2'-Hydroxy-2-hydroxymethyl-3'-O-^-D-(4"-O-methylglucopyranosyl)-dihydrochalcone is found in the fraction of intermediate polarity, in the second band from the starting line.
Korzystnie jest, gdy stosunek masy dodawanego substratu do objętości hodowli wynosi 0,1 mg : 1 cm3.It is advantageous when the ratio of the mass of the added substrate to the volume of the culture is 0.1 mg : 1 cm 3 .
Korzystnie także jest, gdy proces prowadzi się w temperaturze 25 stopni Celsjusza.It is also advantageous if the process is carried out at a temperature of 25 degrees Celsius.
Dodatkowo, korzystnie jest, gdy transformację prowadzi się przez 9 dni.Additionally, it is beneficial if the transformation is carried out for 9 days.
Korzystnie również jest, gdy oczyszczanie prowadzi się wykorzystując cienkowarstwową chromatografię preparatywną w układzie eluującym z chloroformem i metanolem w stosunku objętościowym 9 : 1.It is also advantageous when the purification is carried out using thin-layer preparative chromatography in an eluting system with chloroform and methanol in a volume ratio of 9:1.
Postępując zgodnie z wynalazkiem, w wyniku działania układu enzymatycznego zawartego w komórkach szczepu Beauveria bassiana KCH J1.5, następuje redukcja wiązania podwójnego oraz hydroksylacja przy C-2-CH3 oraz hydroksylacja i przyłączenie 4-metoksy-^-D-glukozy przy C-3’. Uzyskany w ten sposób produkt wydziela się z wodnej kultury mikroorganizmu, znanym sposobem, przez ekstrakcję rozpuszczalnikiem organicznym niemieszającym się z wodą (octan etylu).In accordance with the invention, as a result of the action of the enzymatic system contained in the cells of the Beauveria bassiana KCH J1.5 strain, the reduction of the double bond and hydroxylation at C-2-CH3 and hydroxylation and attachment of 4-methoxy-^-D-glucose at C-3' occur. The product obtained in this way is isolated from the aqueous culture of the microorganism in a known manner, by extraction with an organic solvent immiscible with water (ethyl acetate).
Zasadniczą zaletą wynalazku jest otrzymanie 2’-hydroksy-2-hydroksymetylo-3’-O-/>-D-(4::-O-metyloglukopiranozylo)-dihydrochalkonu w temperaturze pokojowej i przy pH naturalnym dla szczepu oraz wykorzystując mikroorganizm niebędący patogenem ludzkim.The main advantage of the invention is the obtaining of 2'-hydroxy-2-hydroxymethyl-3'-O-/>-D-(4 :: -O-methylglucopyranosyl)-dihydrochalcone at room temperature and at a natural pH for the strain and using a microorganism that is not a human pathogen.
Wykorzystanie biotransformacji, zamiast syntezy chemicznej, umożliwia, w sposób przyjazny dla środowiska, uzyskanie związków o większej biodostępności i aktywności biologicznej, niż użyte substraty.The use of biotransformation instead of chemical synthesis makes it possible, in an environmentally friendly manner, to obtain compounds with greater bioavailability and biological activity than the substrates used.
Wynalazek jest bliżej objaśniony na przykładzie wykonania.The invention is explained in more detail with reference to an example embodiment.
PrzykładExample
Do kolby stożkowej o pojemności 2000 cm3, w której znajduje się 500 cm3 sterylnej pożywki zawierającej 10 g aminobaku i 30 g glukozy, wprowadza się szczep Beauveria bassiana KCH J1.5. Po 72 godzinach jego wzrostu dodaje się 50 mg 2’-hydroksy-2-metylochalkonu o wzorze 1, rozpuszczonego w 1 cm3 dimetylosulfotlenku. Transformację prowadzi się w 25 stopniach Celsjusza przy ciągłym wstrząsaniu przez 9 dni. Następnie mieszaninę poreakcyjną ekstrahuje się dwukrotnie octanem etylu, osusza bezwodnym siarczanem magnezu i odparowuje rozpuszczalnik. Otrzymany ekstrakt oczyszcza się chromatograficznie z zastosowaniem jako eluentu mieszaniny chloroformu i metanolu w stosunku objętościowym 9 : 1. Produkt znajduje się we frakcji o pośredniej polarności, w drugim paśmie od linii startu.Into a 2000 cm 3 conical flask containing 500 cm 3 of sterile medium containing 10 g of aminobac and 30 g of glucose, the Beauveria bassiana KCH J1.5 strain is introduced. After 72 hours of its growth, 50 mg of 2'-hydroxy-2-methylchalcone of formula 1, dissolved in 1 cm 3 of dimethyl sulfoxide, is added. The transformation is carried out at 25 degrees Celsius with continuous shaking for 9 days. Then the reaction mixture is extracted twice with ethyl acetate, dried with anhydrous magnesium sulfate and the solvent is evaporated. The obtained extract is purified by chromatography using a mixture of chloroform and methanol in a volume ratio of 9:1 as eluent. The product is found in the fraction of intermediate polarity, in the second band from the starting line.
Na tej drodze otrzymuje się 4,5 mg 2’-hydroksy-2-hydroksymetylo-3’-O-^-D-(4”-O -metyloglukopiranozylo)-dihydrochalkonu (wydajność 4,8%). Stopień konwersji substratu według HPLC >99%.In this way, 4.5 mg of 2'-hydroxy-2-hydroxymethyl-3'-O-^-D-(4"-O -methylglucopyranosyl)dihydrochalcone is obtained (yield 4.8%). Degree of substrate conversion by HPLC >99%.
Uzyskany produkt charakteryzuje się następującymi danymi spektralnymi.The obtained product is characterized by the following spectral data.
PL 246770 Β1PL 246770 Β1
Opis sygnałów pochodzących z widma 1H NMR (601 MHz, Aceton-de)Description of signals from the 1 H NMR spectrum (601 MHz, Acetone-de)
Claims (5)
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| PL438353A PL246770B1 (en) | 2021-07-05 | 2021-07-05 | 2'-Hydroxy-2-hydroxymethyl-3'-O-β-D-(4''-O-methylglucopyranosyl)-dihydrochalcone and method for the preparation of 2'-hydroxy-2-hydroxymethyl-3'-O-β-D- (4''-O-methylglucopyranosyl)-dihydrochalcone |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| PL438353A PL246770B1 (en) | 2021-07-05 | 2021-07-05 | 2'-Hydroxy-2-hydroxymethyl-3'-O-β-D-(4''-O-methylglucopyranosyl)-dihydrochalcone and method for the preparation of 2'-hydroxy-2-hydroxymethyl-3'-O-β-D- (4''-O-methylglucopyranosyl)-dihydrochalcone |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| PL438353A1 PL438353A1 (en) | 2023-01-09 |
| PL246770B1 true PL246770B1 (en) | 2025-03-03 |
Family
ID=84810938
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| PL438353A PL246770B1 (en) | 2021-07-05 | 2021-07-05 | 2'-Hydroxy-2-hydroxymethyl-3'-O-β-D-(4''-O-methylglucopyranosyl)-dihydrochalcone and method for the preparation of 2'-hydroxy-2-hydroxymethyl-3'-O-β-D- (4''-O-methylglucopyranosyl)-dihydrochalcone |
Country Status (1)
| Country | Link |
|---|---|
| PL (1) | PL246770B1 (en) |
-
2021
- 2021-07-05 PL PL438353A patent/PL246770B1/en unknown
Also Published As
| Publication number | Publication date |
|---|---|
| PL438353A1 (en) | 2023-01-09 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| PL246768B1 (en) | 2'-Hydroxy-2-methyl-3'-O-β-D-(4''-O-methylglucopyranosyl)-dihydrochalcone and method for the preparation of 2'-hydroxy-2-methyl-3'-O-β-D- (4''-O-methylglucopyranosyl)-dihydrochalcone | |
| PL246773B1 (en) | 3-Hydroxy-2-methyl-2'-O-β-D-(4''-O-methylglucopyranosyl)-dihydrochalcone and method for the preparation of 3-hydroxy-2-methyl-2'-O-β-D-(4 ''O-methylglucopyranosyl)-dihydrochalcone | |
| PL246775B1 (en) | 2',4-Dihydroxy-2-methyl-3'-O-β-D-(4''-O-methylglucopyranosyl)-dihydrochalcone and method for the preparation of 2',4-dihydroxy-2-methyl-3'-O-β-D-(4''-O-methylglucopyranosyl)-dihydrochalcone | |
| PL246769B1 (en) | 2',3-Dihydroxy-2-methyl-3'-O-β-D-(4''-O-methylglucopyranosyl)-dihydrochalcone and method for the preparation of 2',3-dihydroxy-2-methyl-3'-O- β-D-(4''-O-methylglucopyranosyl)-dihydrochalcone | |
| PL238972B1 (en) | 6,8-Dichloro-4'-O-β-D-(4"-O-methylglucopyranosyl)-flavone and method of producing 6,8-dichloro-4'-O-β-D-(4"-O-methylglucopyranosyl)-flavone | |
| PL238971B1 (en) | 6-Chloro-4'-0-β-D-(4"-O-methylglucopyranosyl)-flavone and method of producing 6-chloro-4'-O-β-D-(4"-O-methylglucopyranosyl)-flavone | |
| PL241534B1 (en) | 2′-Hydroxy-5'-methyl-3-O-β-D-(4''-O-methylglucopyranosyl)-chalcone and method for the preparation of 2'-hydroxy-5'-methyl-3-O-β-D- (4''-O-methylglucopyranosyl)-chalcone | |
| PL242468B1 (en) | Method for producing 6-Methyl-4'-O-β-D- (4 '- O-methylglucopyranosyl) -flavanone | |
| PL246770B1 (en) | 2'-Hydroxy-2-hydroxymethyl-3'-O-β-D-(4''-O-methylglucopyranosyl)-dihydrochalcone and method for the preparation of 2'-hydroxy-2-hydroxymethyl-3'-O-β-D- (4''-O-methylglucopyranosyl)-dihydrochalcone | |
| PL248132B1 (en) | 2'-Methyl-4'-O-β-D-(4''-O-methylglucopyranosyl)-flavone and method for preparing 2'-methyl-4'-O-β-D-(4''-O-methylglucopyranosyl)-flavone | |
| PL248131B1 (en) | 2'-Methyl-3'-O-β-D-(4''-O-methylglucopyranosyl)-flavone and method for preparing 2'-methyl-3'-O-β-D-(4''-O-methylglucopyranosyl)-flavone | |
| PL242335B1 (en) | 6-Hydroxymethyl-3'-O-β-D-(4'-O-methylglucopyranosyl)-flavanone and method of preparation of 6-hydroxymethyl-3'-O-β-D-(4'-O-methylglucopyranosyl)-flavanone | |
| PL242333B1 (en) | 4'-Hydroxy-6-methylene-O-β-D-(4'-O-methylglucopyranosyl)-flavanone and method of preparation of 4'-hydroxy-6-methylene-O-β-D-(4'-O-methylglucopyranosyl)-flavanone | |
| PL241533B1 (en) | 2-Phenyl-6-methyl-4-O-β-D-(4''-O-methylglucopyranosyl)-chromane and method of producing 2-phenyl-6-methyl-4-O-β-D-(4''-O-methylglucopyranosyl)-chromane | |
| PL246025B1 (en) | 2'-Hydroxy-4-methyl-5'-O-β-D-(4''-O-methylglucopyranosyl)-dihydrochalcone and method for producing 2'-hydroxy-4-methyl-5'-O-β-D-(4''-O-methylglucopyranosyl)-dihydrochalcone | |
| PL238969B1 (en) | 3'-O-β-D-(4"-O-methylglucopyranosyl)-flavan-4-ol and method of preparing 3'-O-β-D-(4"-O-methylglucopyranosyl)-flavan-4-ol | |
| PL246026B1 (en) | 4-Hydroxymethyl-2'-O-β-D-(4''-O-methylglucopyranosyl)-dihydrochalcone and method for producing 4-hydroxymethyl-2'-O-β-D-(4''-O-methylglucopyranosyl)-dihydrochalcone | |
| PL248135B1 (en) | 3'-Hydroxy-2'-methyl-6-O-β-D-(4''-O-methylglucopyranosyl)-flavanone and method for preparing 3'-hydroxy-2'-methyl-6-O-β-D- (4''-O-methylglucopyranosyl)-flavanone | |
| PL248133B1 (en) | 2'-Methyl-6-O-β-D-(4''-O-methylglucopyranosyl)-flavanone and method of preparing of 2'-methyl-6-O-β-D-(4''-O-methylglucopyranosyl)-flavanone | |
| PL248134B1 (en) | 2'-Methyl-5'-O-β-D-(4''-O-methylglucopyranosyl)-flavone and method for preparing 2'-methyl-5'-O-β-D-(4''-O-methylglucopyranosyl) )-flavone | |
| PL247106B1 (en) | 4'-Methylene-O-β-D-(4''-O-methylglucopyranosyl)-flavone and method for preparing 4'-methylene-O-β-D-(4''-O-methylglucopyranosyl)-flavone | |
| PL242469B1 (en) | 3 ', 4'-Dihydroxy-6-hydroxymethylflavanone and 3', 4'-dihydroxy-6-hydroxymethylflavanone production method | |
| PL238785B1 (en) | 4'-Hydroxy-6-O-β-D-(4"-O-methylglucopyranosyl)-flavanone and method for preparing 4'-hydroxy-6-O-β-D-(4"-O-methylglucopyranosyl)-flavanone | |
| PL247107B1 (en) | 4'-Methyl-3-O-β-D-(4''-O-methylglucopyranosyl)-flavone and method of production of 4'-methyl-3-O-β-D-(4''-O-methylglucopyranosyl)-flavone | |
| PL247869B1 (en) | Method for producing 2'-Methyl-3'-O-β-D-(4''-O-methylglucopyranosyl)-flavanone |