WO2023280750A1 - Synthesis of butyrate compounds - Google Patents
Synthesis of butyrate compounds Download PDFInfo
- Publication number
- WO2023280750A1 WO2023280750A1 PCT/EP2022/068389 EP2022068389W WO2023280750A1 WO 2023280750 A1 WO2023280750 A1 WO 2023280750A1 EP 2022068389 W EP2022068389 W EP 2022068389W WO 2023280750 A1 WO2023280750 A1 WO 2023280750A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- formula
- compound
- process according
- compounds
- present
- Prior art date
Links
- 150000004648 butanoic acid derivatives Chemical class 0.000 title abstract description 13
- 238000003786 synthesis reaction Methods 0.000 title abstract description 10
- 230000015572 biosynthetic process Effects 0.000 title abstract description 4
- 150000001875 compounds Chemical class 0.000 claims abstract description 67
- 238000000034 method Methods 0.000 claims description 48
- 239000002904 solvent Substances 0.000 claims description 11
- 125000001424 substituent group Chemical group 0.000 claims description 11
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 8
- 229910052736 halogen Inorganic materials 0.000 claims description 7
- 125000005843 halogen group Chemical group 0.000 claims description 7
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 7
- 235000013305 food Nutrition 0.000 claims description 4
- 229910052757 nitrogen Inorganic materials 0.000 claims description 4
- 239000000010 aprotic solvent Substances 0.000 claims description 3
- 239000012442 inert solvent Substances 0.000 claims description 2
- 239000000543 intermediate Substances 0.000 abstract description 6
- 235000021466 carotenoid Nutrition 0.000 abstract description 3
- -1 carotenoid butyrates Chemical class 0.000 abstract description 3
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 27
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 22
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 16
- DVECBJCOGJRVPX-UHFFFAOYSA-N butyryl chloride Chemical compound CCCC(Cl)=O DVECBJCOGJRVPX-UHFFFAOYSA-N 0.000 description 12
- FERIUCNNQQJTOY-UHFFFAOYSA-M Butyrate Chemical compound CCCC([O-])=O FERIUCNNQQJTOY-UHFFFAOYSA-M 0.000 description 8
- FERIUCNNQQJTOY-UHFFFAOYSA-N Butyric acid Natural products CCCC(O)=O FERIUCNNQQJTOY-UHFFFAOYSA-N 0.000 description 8
- 238000006243 chemical reaction Methods 0.000 description 8
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 8
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 6
- 239000013078 crystal Substances 0.000 description 5
- 238000001914 filtration Methods 0.000 description 5
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 4
- 238000003756 stirring Methods 0.000 description 4
- YNXLOPYTAAFMTN-SBUIBGKBSA-N C([C@H](N)C(=O)N1CCC[C@H]1C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CCCCN)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](C)C(=O)N1[C@@H](CCC1)C(=O)NCC(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](CO)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H](C)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC=1NC=NC=1)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(N)=O)C1=CC=C(O)C=C1 Chemical compound C([C@H](N)C(=O)N1CCC[C@H]1C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CCCCN)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](C)C(=O)N1[C@@H](CCC1)C(=O)NCC(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](CO)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H](C)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC=1NC=NC=1)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(N)=O)C1=CC=C(O)C=C1 YNXLOPYTAAFMTN-SBUIBGKBSA-N 0.000 description 3
- 108010088847 Peptide YY Proteins 0.000 description 3
- 102100029909 Peptide YY Human genes 0.000 description 3
- 210000001035 gastrointestinal tract Anatomy 0.000 description 3
- 239000011261 inert gas Substances 0.000 description 3
- 238000004519 manufacturing process Methods 0.000 description 3
- ZRCXVNZZDQGBQT-XQIHNALSSA-N (3'R)-3'-hydroxy-echinenone Natural products CC(=C/C=C/C=C(C)/C=C/C=C(C)/C=C/C1=C(C)C(=O)CCC1(C)C)C=CC=C(/C)C=CC2=C(C)CC(O)CC2(C)C ZRCXVNZZDQGBQT-XQIHNALSSA-N 0.000 description 2
- DMASLKHVQRHNES-UPOGUZCLSA-N (3R)-beta,beta-caroten-3-ol Chemical compound C([C@H](O)CC=1C)C(C)(C)C=1/C=C/C(/C)=C/C=C/C(/C)=C/C=C/C=C(C)C=CC=C(C)C=CC1=C(C)CCCC1(C)C DMASLKHVQRHNES-UPOGUZCLSA-N 0.000 description 2
- LXBGSDVWAMZHDD-UHFFFAOYSA-N 2-methyl-1h-imidazole Chemical compound CC1=NC=CN1 LXBGSDVWAMZHDD-UHFFFAOYSA-N 0.000 description 2
- ZRCXVNZZDQGBQT-ZMSRUZMRSA-N 3'-Hydroxyechinenone Natural products O=C1C(C)=C(/C=C/C(=C\C=C\C(=C/C=C/C=C(\C=C\C=C(/C=C/C=2C(C)(C)C[C@@H](O)CC=2C)\C)/C)\C)/C)C(C)(C)CC1 ZRCXVNZZDQGBQT-ZMSRUZMRSA-N 0.000 description 2
- ZRCXVNZZDQGBQT-BANQPSJHSA-N 3'-hydroxyechinenone Chemical compound CC=1C(=O)CCC(C)(C)C=1\C=C\C(\C)=C\C=C\C(\C)=C\C=C\C=C(/C)\C=C\C=C(/C)\C=C\C1=C(C)C[C@@H](O)CC1(C)C ZRCXVNZZDQGBQT-BANQPSJHSA-N 0.000 description 2
- DFNMSBYEEKBETA-JZLJSYQFSA-N 3-Hydroxyechinenone Chemical compound C([C@H](O)C(=O)C=1C)C(C)(C)C=1\C=C\C(\C)=C\C=C\C(\C)=C\C=C\C=C(/C)\C=C\C=C(/C)\C=C\C1=C(C)CCCC1(C)C DFNMSBYEEKBETA-JZLJSYQFSA-N 0.000 description 2
- IIYZILPSCTXHAL-UHFFFAOYSA-N 7h-purine;pyridine Chemical compound C1=CC=NC=C1.C1=NC=C2NC=NC2=N1 IIYZILPSCTXHAL-UHFFFAOYSA-N 0.000 description 2
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- 206010061218 Inflammation Diseases 0.000 description 2
- OOUTWVMJGMVRQF-NWYYEFBESA-N Phoenicoxanthin Chemical compound C([C@H](O)C(=O)C=1C)C(C)(C)C=1\C=C\C(\C)=C\C=C\C(\C)=C\C=C\C=C(/C)\C=C\C=C(/C)\C=C\C1=C(C)C(=O)CCC1(C)C OOUTWVMJGMVRQF-NWYYEFBESA-N 0.000 description 2
- OOUTWVMJGMVRQF-DOYZGLONSA-N Phoenicoxanthin Natural products CC(=C/C=C/C=C(C)/C=C/C=C(C)/C=C/C1=C(C)C(=O)C(O)CC1(C)C)C=CC=C(/C)C=CC2=C(C)C(=O)CCC2(C)C OOUTWVMJGMVRQF-DOYZGLONSA-N 0.000 description 2
- CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 description 2
- NBZANZVJRKXVBH-ITUXNECMSA-N all-trans-alpha-cryptoxanthin Natural products CC(=C/C=C/C=C(C)/C=C/C=C(C)/C=C/C1=C(C)CC(O)CC1(C)C)C=CC=C(/C)C=CC2C(=CCCC2(C)C)C NBZANZVJRKXVBH-ITUXNECMSA-N 0.000 description 2
- DMASLKHVQRHNES-ITUXNECMSA-N beta-cryptoxanthin Natural products CC(=C/C=C/C=C(C)/C=C/C=C(C)/C=C/C1=C(C)CC(O)CC1(C)C)C=CC=C(/C)C=CC2=C(C)CCCC2(C)C DMASLKHVQRHNES-ITUXNECMSA-N 0.000 description 2
- 235000002360 beta-cryptoxanthin Nutrition 0.000 description 2
- 239000011774 beta-cryptoxanthin Substances 0.000 description 2
- 229960001701 chloroform Drugs 0.000 description 2
- 239000002178 crystalline material Substances 0.000 description 2
- 239000003629 gastrointestinal hormone Substances 0.000 description 2
- RWSXRVCMGQZWBV-WDSKDSINSA-N glutathione Chemical compound OC(=O)[C@@H](N)CCC(=O)N[C@@H](CS)C(=O)NCC(O)=O RWSXRVCMGQZWBV-WDSKDSINSA-N 0.000 description 2
- 230000004054 inflammatory process Effects 0.000 description 2
- NOESYZHRGYRDHS-UHFFFAOYSA-N insulin Chemical compound N1C(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(NC(=O)CN)C(C)CC)CSSCC(C(NC(CO)C(=O)NC(CC(C)C)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CCC(N)=O)C(=O)NC(CC(C)C)C(=O)NC(CCC(O)=O)C(=O)NC(CC(N)=O)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CSSCC(NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2C=CC(O)=CC=2)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2NC=NC=2)NC(=O)C(CO)NC(=O)CNC2=O)C(=O)NCC(=O)NC(CCC(O)=O)C(=O)NC(CCCNC(N)=N)C(=O)NCC(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC(O)=CC=3)C(=O)NC(C(C)O)C(=O)N3C(CCC3)C(=O)NC(CCCCN)C(=O)NC(C)C(O)=O)C(=O)NC(CC(N)=O)C(O)=O)=O)NC(=O)C(C(C)CC)NC(=O)C(CO)NC(=O)C(C(C)O)NC(=O)C1CSSCC2NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(N)CC=1C=CC=CC=1)C(C)C)CC1=CN=CN1 NOESYZHRGYRDHS-UHFFFAOYSA-N 0.000 description 2
- XLSZMDLNRCVEIJ-UHFFFAOYSA-N methylimidazole Natural products CC1=CNC=N1 XLSZMDLNRCVEIJ-UHFFFAOYSA-N 0.000 description 2
- 239000000203 mixture Substances 0.000 description 2
- DFNMSBYEEKBETA-FXGCUYOLSA-N rac-3-Hydroxyechinenon Natural products CC(=C/C=C/C=C(C)/C=C/C=C(C)/C=C/C1=C(C)C(=O)C(O)CC1(C)C)C=CC=C(/C)C=CC2=C(C)CCCC2(C)C DFNMSBYEEKBETA-FXGCUYOLSA-N 0.000 description 2
- 239000011541 reaction mixture Substances 0.000 description 2
- 125000005270 trialkylamine group Chemical group 0.000 description 2
- 229940086542 triethylamine Drugs 0.000 description 2
- 102000051325 Glucagon Human genes 0.000 description 1
- 108060003199 Glucagon Proteins 0.000 description 1
- DTHNMHAUYICORS-KTKZVXAJSA-N Glucagon-like peptide 1 Chemical compound C([C@@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](C)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCCCN)C(=O)NCC(=O)N[C@@H](CCCNC(N)=N)C(N)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCCCN)NC(=O)[C@H](C)NC(=O)[C@H](C)NC(=O)[C@H](CCC(N)=O)NC(=O)CNC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CO)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@@H](NC(=O)CNC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C)NC(=O)[C@@H](N)CC=1N=CNC=1)[C@@H](C)O)[C@@H](C)O)C(C)C)C1=CC=CC=C1 DTHNMHAUYICORS-KTKZVXAJSA-N 0.000 description 1
- 101800000224 Glucagon-like peptide 1 Proteins 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
- 108010024636 Glutathione Proteins 0.000 description 1
- 102000004877 Insulin Human genes 0.000 description 1
- 108090001061 Insulin Proteins 0.000 description 1
- 102100040918 Pro-glucagon Human genes 0.000 description 1
- 210000000577 adipose tissue Anatomy 0.000 description 1
- 230000003110 anti-inflammatory effect Effects 0.000 description 1
- 239000003963 antioxidant agent Substances 0.000 description 1
- 230000003078 antioxidant effect Effects 0.000 description 1
- 235000006708 antioxidants Nutrition 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 210000001072 colon Anatomy 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 239000000446 fuel Substances 0.000 description 1
- MASNOZXLGMXCHN-ZLPAWPGGSA-N glucagon Chemical compound C([C@@H](C(=O)N[C@H](C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(O)=O)C(C)C)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](C)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CO)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CO)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@@H](NC(=O)CNC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](N)CC=1NC=NC=1)[C@@H](C)O)[C@@H](C)O)C1=CC=CC=C1 MASNOZXLGMXCHN-ZLPAWPGGSA-N 0.000 description 1
- 229960004666 glucagon Drugs 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 229960003180 glutathione Drugs 0.000 description 1
- 244000005709 gut microbiome Species 0.000 description 1
- 229940125396 insulin Drugs 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- 239000012452 mother liquor Substances 0.000 description 1
- 210000003205 muscle Anatomy 0.000 description 1
- SYSQUGFVNFXIIT-UHFFFAOYSA-N n-[4-(1,3-benzoxazol-2-yl)phenyl]-4-nitrobenzenesulfonamide Chemical class C1=CC([N+](=O)[O-])=CC=C1S(=O)(=O)NC1=CC=C(C=2OC3=CC=CC=C3N=2)C=C1 SYSQUGFVNFXIIT-UHFFFAOYSA-N 0.000 description 1
- 230000036542 oxidative stress Effects 0.000 description 1
- 210000000496 pancreas Anatomy 0.000 description 1
- GCYXWQUSHADNBF-AAEALURTSA-N preproglucagon 78-108 Chemical compound C([C@@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](C)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCCCN)C(=O)NCC(=O)N[C@@H](CCCNC(N)=N)C(=O)NCC(O)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCCCN)NC(=O)[C@H](C)NC(=O)[C@H](C)NC(=O)[C@H](CCC(N)=O)NC(=O)CNC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CO)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@@H](NC(=O)CNC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C)NC(=O)[C@@H](N)CC=1N=CNC=1)[C@@H](C)O)[C@@H](C)O)C(C)C)C1=CC=CC=C1 GCYXWQUSHADNBF-AAEALURTSA-N 0.000 description 1
- 230000000770 proinflammatory effect Effects 0.000 description 1
- 230000028327 secretion Effects 0.000 description 1
- 235000021391 short chain fatty acids Nutrition 0.000 description 1
- 150000004666 short chain fatty acids Chemical class 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 230000004584 weight gain Effects 0.000 description 1
- 235000019786 weight gain Nutrition 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C403/00—Derivatives of cyclohexane or of a cyclohexene or of cyclohexadiene, having a side-chain containing an acyclic unsaturated part of at least four carbon atoms, this part being directly attached to the cyclohexane or cyclohexene or cyclohexadiene rings, e.g. vitamin A, beta-carotene, beta-ionone
- C07C403/02—Derivatives of cyclohexane or of a cyclohexene or of cyclohexadiene, having a side-chain containing an acyclic unsaturated part of at least four carbon atoms, this part being directly attached to the cyclohexane or cyclohexene or cyclohexadiene rings, e.g. vitamin A, beta-carotene, beta-ionone having side-chains containing only carbon and hydrogen atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C403/00—Derivatives of cyclohexane or of a cyclohexene or of cyclohexadiene, having a side-chain containing an acyclic unsaturated part of at least four carbon atoms, this part being directly attached to the cyclohexane or cyclohexene or cyclohexadiene rings, e.g. vitamin A, beta-carotene, beta-ionone
- C07C403/24—Derivatives of cyclohexane or of a cyclohexene or of cyclohexadiene, having a side-chain containing an acyclic unsaturated part of at least four carbon atoms, this part being directly attached to the cyclohexane or cyclohexene or cyclohexadiene rings, e.g. vitamin A, beta-carotene, beta-ionone having side-chains substituted by six-membered non-aromatic rings, e.g. beta-carotene
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2601/00—Systems containing only non-condensed rings
- C07C2601/12—Systems containing only non-condensed rings with a six-membered ring
- C07C2601/16—Systems containing only non-condensed rings with a six-membered ring the ring being unsaturated
Definitions
- the present invention relates to a synthesis of specific carotenoid butyrates as well as to new compounds and their use.
- Butyrate compounds are very useful compounds, either as such or as intermediates in organic synthesis.
- Butyrates are seen as very useful and healthy compounds.
- butyrates fuels colonocytes help provide an oxygen- free environment in which beneficial gut microbes thrive. This keeps inflammation in check, gut cells healthy, and gut bacteria in a good state.
- Butyrates stop some of the pro-inflammatory substances in the human body from working.
- the anti-inflammatory effect of butyrate reduces oxidative stress and controls the damage caused by free radicals.
- GLP-1 glucagon-like peptide-1
- PYY peptide YY
- butyrates can be used as intermediates in organic synthesis to produce i.e. useful carotenoid compounds.
- the main problem with the butyrates is the strong (fishy) odour. Such an odour is such that most persons are not able to swallow such a compound even in very low concentration.
- the goal of the present invention was to provide a way to produce butyrate compounds having all advantages but not having the strong unpleasant odour in a good yield.
- the present invention relates to a process (P) for producing compounds of formula
- R 4 is -0(C0)(CH 2 ) 2 CH 3 , -OH or -H
- Ri is a moiety wherein
- R 3 , R 4 and R 5 are -0(C0)(CH 2 ) 2 CH 3 moiety, by reacting a compound of formula (G) wherein R 3 is -OH or -H, and R 4 is -OH or -H, and
- Ri is a moiety wherein
- R 3 , R 4 and Rs is -OH, with the proviso that at least one of the substituents R 3 , R 4 and Rs is -OH, with a compound of formula (II) wherein X is a halogen (such as Cl, Br, or F) or a group -0(C0(CH2)2CH3, in the presence of at least one base.
- X is a halogen (such as Cl, Br, or F) or a group -0(C0(CH2)2CH3, in the presence of at least one base.
- Preferred compounds of formula (I) are those of formula (la), (lb) (lc), (Id) and (le) wherein the substituents R3, R4 and Rs have the same definition as defined above and wherein at least one of R3, R4 and Rs is a -0(C0)(CH2)2CH3 moiety.
- the OH group of the compounds of formula (G) are the transformed into the butyrate when carrying out the process according to the present invention.
- the present invention relates to a process (P1) for producing compounds of formula (la)
- R 3 is -OH or -H and Rs is -OH or -H, with the proviso that at least one of the substituents R 3 , and Rs is -OH, with a compound of formula (II) wherein X is a halogen or a group -0(C0(CH2)2CH3, in the presence of at least one base.
- the present invention relates to a process (P2) for producing compounds of formula (lb)
- R 3 is -0(C0)(CH 2 ) 2 CH3, by reacting a compound of formula (I’b) with a compound of formula (II) wherein
- X is a halogen or a group 0(C0(CH 2 ) 2 CH 3 in the presence of at least one base.
- the present invention relates to a process (P3) for producing compounds of formula (lc) wherein
- R 4 is -0(C0)(CH 2 ) 2 CH3, -OH or -H and Rs is -0(C0)(CH 2 )2CH 3 , -OH or -H, with the proviso that at least one of the substituent R 4 and Rs is a -0(C0)(CH 2 ) 2 CH3 moiety, by reacting a compound of formula (Go) wherein
- R 4 is -OH or -H and Rs is -OH or -H, with the proviso that at least one of the substituents R 3 and Rs is -OH, with a compound of formula (II) wherein
- X is a halogen or a group -0(C0(CH 2 ) 2 CH 3 and in the presence of at least one base.
- the present invention relates to a process (P4) for producing compounds of formula (Id)
- R 3 is -0(C0)(CH 2 ) 2 CH 3 , by reacting a compound of formula (I’d) with a compound of formula (II) wherein X is a halogen or a group -0(C0(CH 2 ) 2 CH 3 and in the presence of at least one base.
- the present invention relates to a process (P5) for producing compounds of formula (le)
- R 4 is -0(C0)(CH 2 )2CH 3 , by reacting a compound of formula (I’e) with a compound of formula (II) wherein
- X is a halogen or a group -0(C0(CH2)2CH3 in the presence of at least one base.
- the process according to the present invention is carried out in the presence of at least one base.
- the base is a nitrogen base.
- Suitable bases are pyrimidine, pyridine purine, methylimidazole or trialkyl amines, (e.g. triethyl amine, diisopropylethyl amine).
- the present invention relates to a process (P6), which is process (P), (P1), (P2), (P3), (P4) or (P5), wherein the at least one base is a nitrogen base. Therefore, the present invention relates to a process (P6’), which is process (P6), wherein the nitrogen base is chosen from the group consisting of pyrimidine, pyridine purine, methylimidazole or trialkyl amines, (e.g. triethyl amine, diisopropylethyl amine).
- the base is added to the reaction mixture in a molar ratio of 1 :1 : to 3 :1 in view of the compound of formula (II).
- the present invention relates to a process (P7), which is process (P), (P1), (P2), (P3), (P4), (P5), (P6) or (P6’), wherein the at least one base is used in a molar ratio of 1 :1 : to 3 :1 in view of the compound of formula (II).
- the compound of formula (II) is used in excess in view of the compound of formula (G). It is clear that when two OH groups in compounds of formula (G) are to be acetylated the molar excess of the compound of formula (II) is more than 2.
- the molar ratio of the compound of formula (II) to the compound of formula (I’) is 1 : 1 to 3:1 , when one OH group in the compound of formula (G) is to be acetylated.
- the molar ratio of the compound of formula (II) to the compound of formula (I’) is 2:1 to 6:1 , when two OH groups in the compound of formula (I’) are to be acetylated.
- the present invention relates to a process (P8), which is process (P), (P1), (P2), (P3), (P4), (P5), (P6), (P6’) or (P7), wherein the molar ratio of the compound of formula (II) to the compound of formula (G) is 1 :1 to 3:1 , when one OH group in the compound of formula (G) is to be acetylated.
- the present invention relates to a process (P8’), which is process (P), (P1), (P2), (P3), (P4), (P5), (P6), (P6’) or (P7), wherein the molar ratio of the compound of formula (II) to the compound of formula (G) is 2:1 to 6:1 , when two OH groups in the compound of formula (G) are to be acetylated.
- the process according to the present invention can be carried without any solvent or it can be carried out in at least one inert solvent.
- the solvent is usually a polar aprotic or apolar aprotic solvent.
- Suitable solvents are dichloromethane or trichloromethane.
- the present invention relates to a process (P9), which is process (P), (P1), (P2), (P3), (P4), (P5), (P6), (P6’), (P7), (P8) or (P8’), wherein the process is carried without any solvent.
- the present invention relates to a process (P10), which is process (P), (P1), (P2), (P3), (P4), (P5), (P6), (P6’), (P7), (P8) or (P8’), wherein the process is carried in at least one solvent, wherein the solvent is a polar aprotic or apolar aprotic solvent.
- the present invention relates to a process ( P 10’ ) , which is process (P10), wherein the solvent is chosen from the group consisting of dichloromethane and trichloromethane.
- the process according to the present invention is carried out at a temperature of 10°C to 50° C.
- the present invention relates to a process (P11), which is process (P), (P1), (P2), (P3), (P4), (P5), (P6), (P6’), (P7), (P8), (P8’), (P9), (P10) or (P10’), wherein the process is carried out at a temperature of 10°C to 50° C.
- the product (compound of formula (I)) is isolated using commonly known methods. Usually using filtration.
- the product (compound of formula (I)) can the also be purified further.
- the present invention also relates to new compounds.
- the new compounds are the ones of formulae (If) to (lo)
- the compounds of formula (I) can be used as such or in any formulation in the field of food, feed, pharma and personal care applications.
- the compounds of formula (I) can also be used as intermediates in organic synthesis.
- the present invention relates to the use of the compounds of formula (la), (lb) (lc), (Id) and/or (le) in food, feed, pharma and personal care applications.
- the present invention relates to the use of the compounds of formula (la), (lb) (lc), (Id) and/or (le) as intermediates in organic synthesis.
- the present invention relates to the use of the compounds of formula (le),
Abstract
The present invention relates to a synthesis of specific carotenoid butyrates as well as to new compounds and their use. Butyrate compounds are very useful compounds, either as such or as intermediates in organic synthesis.
Description
Synthesis of Butyrate Compounds
The present invention relates to a synthesis of specific carotenoid butyrates as well as to new compounds and their use. Butyrate compounds are very useful compounds, either as such or as intermediates in organic synthesis.
Butyrates are seen as very useful and healthy compounds.
It is known that butyrates fuels colonocytes, and in return these cells help provide an oxygen- free environment in which beneficial gut microbes thrive. This keeps inflammation in check, gut cells healthy, and gut bacteria in a good state.
Higher butyrate levels have been shown to increase levels of glutathione, an antioxidant produced in the body’s cells which neutralises free radicals in the gut. This is good because free radicals are linked to inflammation and many diseases.
Butyrates stop some of the pro-inflammatory substances in the human body from working. The anti-inflammatory effect of butyrate reduces oxidative stress and controls the damage caused by free radicals.
Furthermore, research shows that butyrates enhance the secretion of gut hormones like glucagon-like peptide-1 (GLP-1) and peptide YY (PYY). GLP-1 increases insulin production and reduces glucagon production in the pancreas. PYY increases the uptake of glucose in both muscles and fatty tissue.
Increased production of short-chain fatty acids, including butyrate in the colon, increases the release of these gut hormones, indicating potential benefits for managing blood sugar levels and preventing weight gain.
Furthermore, butyrates can be used as intermediates in organic synthesis to produce i.e. useful carotenoid compounds.
The main problem with the butyrates is the strong (fishy) odour. Such an odour is such that most persons are not able to swallow such a compound even in very low concentration.
Due to the importance of butyrates, the goal of the present invention was to provide a way to produce butyrate compounds having all advantages but not having the strong unpleasant odour in a good yield.
Surprisingly, it was found that specific new butyrate compounds as defined by the formula below can be obtained in good yields by a new and easy process.
Therefore, the present invention relates to a process (P) for producing compounds of formula
(the * always shows where it is attached to the backbone) wherein
Rs is -0(C0)(CH2)2CH3, -OH or -H, and R4 is -0(C0)(CH2)2CH3, -OH or -H, and Ri is a moiety
wherein
Rs is -0(C0)(CH2)2CH3, -OH or -H, with the proviso that at least one of the substituent R3, R4 and R5 is a -0(C0)(CH2)2CH3 moiety, by reacting a compound of formula (G)
wherein R3 is -OH or -H, and R4 is -OH or -H, and
Ri is a moiety
wherein
Rs is -OH or -H, with the proviso that at least one of the substituents R3, R4 and Rs is -OH, with a compound of formula (II)
wherein
X is a halogen (such as Cl, Br, or F) or a group -0(C0(CH2)2CH3, in the presence of at least one base.
Preferred compounds of formula (I) are those of formula (la), (lb) (lc), (Id) and (le)
wherein the substituents R3, R4 and Rs have the same definition as defined above and wherein at least one of R3, R4 and Rs is a -0(C0)(CH2)2CH3 moiety.
The OH group of the compounds of formula (G) are the transformed into the butyrate when carrying out the process according to the present invention.
Therefore, the present invention relates to a process (P1) for producing compounds of formula (la)
Rs is -0(C0)(CH2)2CH3, -OH or -H and Rs is -0(C0)(CH2)2CH3, -OH or -H, with the proviso that at least one of the substituent R3 and Rs is a -0(C0)(CH2)2CH3 moiety, by reacting a compound of formula (I’a)
R3 is -OH or -H and Rs is -OH or -H, with the proviso that at least one of the substituents R3, and Rs is -OH, with a compound of formula (II)
wherein
X is a halogen or a group -0(C0(CH2)2CH3, in the presence of at least one base.
Therefore, the present invention relates to a process (P2) for producing compounds of formula (lb)
R3 is -0(C0)(CH2)2CH3, by reacting a compound of formula (I’b)
with a compound of formula (II)
wherein
X is a halogen or a group 0(C0(CH2)2CH3 in the presence of at least one base.
Therefore, the present invention relates to a process (P3) for producing compounds of formula (lc)
wherein
R4 is -0(C0)(CH2)2CH3, -OH or -H and Rs is -0(C0)(CH2)2CH3, -OH or -H, with the proviso that at least one of the substituent R4 and Rs is a -0(C0)(CH2)2CH3 moiety, by reacting a compound of formula (Go)
wherein
R4 is -OH or -H and Rs is -OH or -H, with the proviso that at least one of the substituents R3 and Rs is -OH, with a compound of formula (II)
wherein
X is a halogen or a group -0(C0(CH2)2CH3 and
in the presence of at least one base.
Therefore, the present invention relates to a process (P4) for producing compounds of formula (Id)
R3 is -0(C0)(CH2)2CH3, by reacting a compound of formula (I’d)
with a compound of formula (II)
wherein X is a halogen or a group -0(C0(CH2)2CH3 and in the presence of at least one base.
Therefore, the present invention relates to a process (P5) for producing compounds of formula (le)
R4 is -0(C0)(CH2)2CH3, by reacting a compound of formula (I’e)
with a compound of formula (II)
wherein
X is a halogen or a group -0(C0(CH2)2CH3 in the presence of at least one base.
The process according to the present invention is carried out in the presence of at least one base. Usually and preferably the base is a nitrogen base. Suitable bases are pyrimidine, pyridine purine, methylimidazole or trialkyl amines, (e.g. triethyl amine, diisopropylethyl amine).
Therefore, the present invention relates to a process (P6), which is process (P), (P1), (P2), (P3), (P4) or (P5), wherein the at least one base is a nitrogen base.
Therefore, the present invention relates to a process (P6’), which is process (P6), wherein the nitrogen base is chosen from the group consisting of pyrimidine, pyridine purine, methylimidazole or trialkyl amines, (e.g. triethyl amine, diisopropylethyl amine).
The base is added to the reaction mixture in a molar ratio of 1 :1 : to 3 :1 in view of the compound of formula (II).
Therefore, the present invention relates to a process (P7), which is process (P), (P1), (P2), (P3), (P4), (P5), (P6) or (P6’), wherein the at least one base is used in a molar ratio of 1 :1 : to 3 :1 in view of the compound of formula (II).
The compound of formula (II) is used in excess in view of the compound of formula (G). It is clear that when two OH groups in compounds of formula (G) are to be acetylated the molar excess of the compound of formula (II) is more than 2.
The molar ratio of the compound of formula (II) to the compound of formula (I’) is 1 : 1 to 3:1 , when one OH group in the compound of formula (G) is to be acetylated.
The molar ratio of the compound of formula (II) to the compound of formula (I’) is 2:1 to 6:1 , when two OH groups in the compound of formula (I’) are to be acetylated.
Therefore, the present invention relates to a process (P8), which is process (P), (P1), (P2), (P3), (P4), (P5), (P6), (P6’) or (P7), wherein the molar ratio of the compound of formula (II) to the compound of formula (G) is 1 :1 to 3:1 , when one OH group in the compound of formula (G) is to be acetylated.
Therefore, the present invention relates to a process (P8’), which is process (P), (P1), (P2), (P3), (P4), (P5), (P6), (P6’) or (P7), wherein the molar ratio of the compound of formula (II) to the compound of formula (G) is 2:1 to 6:1 , when two OH groups in the compound of formula (G) are to be acetylated.
The process according to the present invention can be carried without any solvent or it can be carried out in at least one inert solvent.
When using a solvent the solvent is usually a polar aprotic or apolar aprotic solvent.
Suitable solvents are dichloromethane or trichloromethane.
Therefore, the present invention relates to a process (P9), which is process (P), (P1), (P2), (P3), (P4), (P5), (P6), (P6’), (P7), (P8) or (P8’), wherein the process is carried without any solvent.
Therefore, the present invention relates to a process (P10), which is process (P), (P1), (P2), (P3), (P4), (P5), (P6), (P6’), (P7), (P8) or (P8’), wherein the process is carried in at least one solvent, wherein the solvent is a polar aprotic or apolar aprotic solvent.
Therefore, the present invention relates to a process ( P 10’ ) , which is process (P10), wherein the solvent is chosen from the group consisting of dichloromethane and trichloromethane.
The process according to the present invention is carried out at a temperature of 10°C to 50° C.
Therefore, the present invention relates to a process (P11), which is process (P), (P1), (P2), (P3), (P4), (P5), (P6), (P6’), (P7), (P8), (P8’), (P9), (P10) or (P10’), wherein the process is carried out at a temperature of 10°C to 50° C.
At the end of the reaction process the product (compound of formula (I)) is isolated using commonly known methods. Usually using filtration.
The product (compound of formula (I)) can the also be purified further.
The present invention also relates to new compounds. The new compounds are the ones of formulae (If) to (lo)
As stated above the compounds of formula (I) can be used as such or in any formulation in the field of food, feed, pharma and personal care applications.
The compounds of formula (I) can also be used as intermediates in organic synthesis.
Preferably the present invention relates to the use of the compounds of formula (la), (lb) (lc), (Id) and/or (le) in food, feed, pharma and personal care applications.
Preferably the present invention relates to the use of the compounds of formula (la), (lb) (lc), (Id) and/or (le) as intermediates in organic synthesis.
More preferably the present invention relates to the use of the compounds of formula
(le), (If) (Ig), (Ih), (li), (Ij), (Ik), (Im), (In) and/or (lo) in food, feed, pharma and personal care applications.
Preferably the present invention relates to the use of the compounds of formula (le),
(Lf) (Ig), (Ih), (li), (Ij), (Ik), (Im), (In) and/or (lo) as intermediates in organic synthesis.
The following examples illustrate the invention further without limiting it. All percentages and parts, which are given, are related to the weight and the temperatures are given in °C, and the pressures are absolute pressures when not otherwise stated.
Examples
Example 1:
A solution of beta-cryptoxanthin (1 .705 g, 3.00 mmol) in dichloromethane (30 ml) was cooled to 17 °C with a cooling bath. To this suspension, pyridine (0.291 ml, 3.60 mmol) and butyryl chloride (0.378 ml, 3.60 mmol) were added drop wise within 4min, whereby the temperature increased to 20 °C. After 3h at room temperature only partial conversion was observed (TLC). Therefore, more pyridine (0.097 ml, 1.200 mmol) and butyryl chloride (0.126 ml, 1.200 mmol) were added drop wise and stirring was continued. After another 1 h 30min the reaction was complete and ethanol (20 ml) was added slowly to remove access of butyryl chloride. The product was crystallized from dichloromethane / ethanol (30 ml). The crystalline product was removed by filtration, washed with ethanol (2 x 5.0 ml) and dried overnight in vacuo (10 mbar). Beta-cryptoxanthin butyrate was obtained as purple crystals (1.72 g) in 92% yield.
Example 2
Under inert gas atmosphere, to a solution of adonirubin (0.254 g, 0.385 mmol) in dichloromethane (10 ml) was added pyridine (0.050 ml, 0.616 mmol) and butyryl chloride (0.065 ml, 0.616 mmol) drop wise within 2min, whereby the temperature increased to 23.5 °C. After 90min at room temperature only partial conversion was observed (TLC). Therefore, after 1.5h more pyridine (0.050 ml, 0.616 mmol) and butyryl chloride (0.068 ml, 0.616 mmol) were added drop wise and stirring was continued. After another 3h 45min the reaction solution was warmed to 35 °C for 30min. Then, ethanol (10 ml) was added slowly to remove access of butyryl chloride. The product was crystallized from dichloromethane / ethanol (10 ml). The crystalline product was removed by filtration (G3 sinter) and washed with ethanol (2 x 1.0 ml). Additional crystals were recovered from the mother liquor by filtration over a membrane filter. These crystals were also rinsed with ethanol (2 x 1.0 ml). The combined crystalline material was dried in high vacuo for 2h at 35 °C. Adonirubin butyrate was obtained as purple crystals (0.127 g) in 50% yield.
Example 3
Under inert gas atmosphere, to a solution of 3-hydroxyechinenone (0.45 g, 0.794 mmol) in dichloromethane (10 ml) was added pyridine (0.103 ml, 1.270 mmol) and butyryl chloride (0.133 ml, 1.270 mmol) drop wise 6min, whereby the temperature increased to 21 °C. After 60min at room temperature only partial conversion was observed (TLC). Therefore, subsequently more pyridine (0.077 ml, 0.953 mmol) and butyryl chloride (0.10 ml, 0.935 mmol)
were added drop wise and stirring was continued. After another 3h 45min, the reaction mixture warmed to 35 °C for 30min. Then, ethanol (7 ml) was added slowly to remove access of butyryl chloride. The product was crystallized from dichloromethane / ethanol (10 ml). The crystalline product was removed by filtration (G3 sinter) and washed with ethanol (2 x 2.0 ml). The crystalline material was dried overnight at r.t. and 10mbar. 3-Hydroxyechinenone butyrate was obtained as purple crystals (0.127 g) in 54% yield.
Example 4
Under inert gas atmosphere, to a solution of 3’-hydroxyechinenone (0.45 g, 0.780 mmol) in dichloromethane (10 ml) was added pyridine (0.076 ml, 0.935 mmol) and butyryl chloride (0.098 ml, 0.935 mmol) drop wise within 6min, whereby the temperature increased to 21 °C.
After 90min at room temperature only partial conversion was observed (TLC). Therefore, after 1 h 45min more pyridine (0.025 ml, 0.312 mmol) and butyryl chloride (0.033 ml, 0.312 mmol) were added drop wise and stirring was continued. After another 1h 15min at r.t. the reaction was completed. Then, ethanol (7 ml) was added slowly to remove access of butyryl chloride. The solvents were removed under reduced pressure and the resulting oily residue was dried in high vacuum. 3’-Hydroxyechinenone butyrate was obtained as dark-red amorphous solid (0.43 g) as a mixture of three isomers in 87% yield (sum of isomers).
Claims
Claims
(the * always shows where it is attached to the backbone) wherein
R3 is -0(C0)(CH2)2CH3, -OH or -H, and R4 is -0(C0)(CH2)2CH3, -OH or -H, and Ri is a moiety
wherein
Rs is -0(C0)(CH2)2CH3, -OH or -H, with the proviso that at least one of the substituent R3, R4 and Rs is a -0(C0)(CH2)2CH3 moiety, by reacting a compound of formula (I’)
Wherein R3 is -OH or -H, and R4 is -OH or -H, and Ri is a moiety
wherein
Rs is -OH or -H, with the proviso that at least one of the substituents R3, R4 and Rs is -OH, with a compound of formula (II)
wherein
X is a halogen (such as Cl, Br, or F) or a group -0(C0(CH2)2CH3, in the presence of at least one base.
2. Process according to claim 1 , wherein a compound of formula (I’a)
wherein
R3 is -OH or -H and Rs is -OH or -H, with the proviso that at least one of the substituents R3 and R5 is -OH, is used.
3. Process according to claim 1 , wherein a compound of formula (I’b)
4. Process according to claim 1 , wherein a compound of formula (I’c)
wherein
R4 is -OH or -H and
Rs is -OH or -H, with the proviso that at least one of the substituents R4 and R5 is -OH, is used.
5. Process according to claim 1 , wherein a compound of formula (I’d)
6. Process according to claim 1 , wherein a compound of formula (I’e)
7. Process according to anyone of the preceding claims, wherein the at least one base is a nitrogen base.
8. Process according to anyone of the preceding claims, wherein the at least one base is used in a molar ratio of 1 :1 : to 3 :1 in view of the compound of formula (II).
9. Process according to anyone of the preceding claims, wherein the molar ratio of the compound of formula (II) to the compound of formula (G) is 1 :1 to 3:1 , when one OH group in the compound of formula (I’) is to be acetylated.
10. Process according to anyone of the preceding claims, wherein the process is carried without any solvent.
11. Process according to anyone of the preceding claims 1 - 9, wherein the process is carried in at least one inert solvent.
12. Process according to claim 11 , wherein the solvent is a polar aprotic or apolar aprotic solvent.
13. Process according to anyone of the preceding claims, wherein the process is carried out at a temperature of 10°C to 50° C.
14. Compounds of formulae
15. Use of at least one compound of formula (I) in food, feed, pharma and personal care applications.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP21184781.9 | 2021-07-09 | ||
| EP21184781 | 2021-07-09 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| WO2023280750A1 true WO2023280750A1 (en) | 2023-01-12 |
Family
ID=77050793
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| PCT/EP2022/068389 WO2023280750A1 (en) | 2021-07-09 | 2022-07-04 | Synthesis of butyrate compounds |
Country Status (1)
| Country | Link |
|---|---|
| WO (1) | WO2023280750A1 (en) |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP3801496A1 (en) * | 2018-06-05 | 2021-04-14 | Flagship Pioneering Innovations V, Inc. | Active agents and methods of their use for the treatment of metabolic disorders and nonalcoholic fatty liver disease |
-
2022
- 2022-07-04 WO PCT/EP2022/068389 patent/WO2023280750A1/en unknown
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP3801496A1 (en) * | 2018-06-05 | 2021-04-14 | Flagship Pioneering Innovations V, Inc. | Active agents and methods of their use for the treatment of metabolic disorders and nonalcoholic fatty liver disease |
Non-Patent Citations (2)
| Title |
|---|
| KARRER P. ET AL: "-1195 - Pflanzenfarbstoffe XLIII l Zur Kenntnis der Carotinoide der Bluten", vol. 1, 1 January 1932 (1932-01-01), pages 1195 - 1204, XP055874841, Retrieved from the Internet <URL:https://onlinelibrary.wiley.com/doi/10.1002/hlca.193201501134> [retrieved on 20211220], DOI: 10.1002/hlca.193201501134 * |
| KARRER P. ET AL: "Pflanzenfarbstoffe XXVI. Über weitere Ester des Xanthophylls", HELVETICA CHIMICA ACTA, vol. 13, no. 5, 1 October 1930 (1930-10-01), pages 1099 - 1102, XP055874835, ISSN: 0018-019X, DOI: 10.1002/hlca.19300130533 * |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| JP3174410B2 (en) | Preparation of chlorosulfate and sulfamate derivatives of 2,3: 4,5-bis-O- (1-methylethylidene) -β-D-fructopyranose and (1-methylcyclohexyl) methanol | |
| FR2565232A1 (en) | NOVEL FATTY ACID DIESTERS AND A, A-TREHALOSE, PROCESS FOR THEIR PREPARATION AND THERAPEUTIC USE THEREOF | |
| DE2033359C3 (en) | Acylpropanediol- (1,3) -phosphoric acid monocholine ester and process for their preparation | |
| WO2023280750A1 (en) | Synthesis of butyrate compounds | |
| EP0217207B1 (en) | 2-amino purines substituted in positions 6 and 9, their use, medicaments containing these purines and processes for their preparation | |
| DE60202483T2 (en) | PROCESS FOR THE PREPARATION OF L-RIBAVIRIN | |
| EP0024525A1 (en) | Process for the preparation of luciferin and its derivatives | |
| FR2499577A1 (en) | SUBSTITUTED 1- (2-CHLOROETHYL) -1-NITROSOUREES-3-SUBSTITUTED BY SUGAR REST, PARTICULARLY USEFUL AS ANTITUMOR AGENTS AND PROCESS FOR THE PREPARATION THEREOF | |
| JPS634543B2 (en) | ||
| WO2023198486A1 (en) | Urolithin butyrate compounds | |
| WO2023052274A1 (en) | Synthesis of 2-isopropyl-5-methylphenyl butyrate | |
| DE2757506C2 (en) | Process for the preparation of Piperonylidencrotonsaureamiden | |
| WO2020182227A1 (en) | Preparation method for high purity liraglutide side chain | |
| WO2023099297A1 (en) | Synthesis of hmo butyrate | |
| WO2023012205A1 (en) | Synthesis of specific butyrate compounds | |
| US20230103507A1 (en) | Method for preparing 3,6-dichloropyrazine-2-carbonitrile | |
| Kim et al. | Free radical-mediated carboxylation by radical reaction of alkyl iodides with methyl oxalyl chloride | |
| WO2023078722A1 (en) | Synthesis of pantothenic acid butyrate | |
| IL37439A (en) | The preparation of 3-amino-2-cyanoacrylamide | |
| JPS609490B2 (en) | Production method of cyclohexanedione-(1,3) | |
| JP2719841B2 (en) | Thiourea derivative and method for producing the same | |
| US6066754A (en) | Process for manufacturing N-alkoxy(or aryloxy)carbonyl isothiocyanate derivatives using N,N-dialkylarylamine as catalyst | |
| WO2022162121A1 (en) | New butyrate compounds | |
| DE2428157A1 (en) | PROCESS FOR THE PREPARATION OF 2-ARYLAS-TRIAZINE-3,5 (2H, 4H) -DIONES | |
| DE2219601A1 (en) | beta-lactams and processes for their preparation |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| 121 | Ep: the epo has been informed by wipo that ep was designated in this application |
Ref document number: 22735927 Country of ref document: EP Kind code of ref document: A1 |
|
| NENP | Non-entry into the national phase |
Ref country code: DE |