CA2918955C - Methods of preparing nicotinamide riboside and derivatives thereof - Google Patents
Methods of preparing nicotinamide riboside and derivatives thereof Download PDFInfo
- Publication number
- CA2918955C CA2918955C CA2918955A CA2918955A CA2918955C CA 2918955 C CA2918955 C CA 2918955C CA 2918955 A CA2918955 A CA 2918955A CA 2918955 A CA2918955 A CA 2918955A CA 2918955 C CA2918955 C CA 2918955C
- Authority
- CA
- Canada
- Prior art keywords
- unsubstituted
- substituted
- formula
- compound
- anion
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Active
Links
- 238000000034 method Methods 0.000 title claims abstract description 110
- JLEBZPBDRKPWTD-TURQNECASA-O N-ribosylnicotinamide Chemical compound NC(=O)C1=CC=C[N+]([C@H]2[C@@H]([C@H](O)[C@@H](CO)O2)O)=C1 JLEBZPBDRKPWTD-TURQNECASA-O 0.000 title abstract description 54
- 235000020956 nicotinamide riboside Nutrition 0.000 title abstract description 53
- 239000011618 nicotinamide riboside Substances 0.000 title abstract description 53
- 150000001875 compounds Chemical class 0.000 claims abstract description 105
- 125000003118 aryl group Chemical group 0.000 claims abstract description 48
- 150000001450 anions Chemical class 0.000 claims abstract description 34
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 11
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims abstract description 11
- 125000003342 alkenyl group Chemical group 0.000 claims abstract description 10
- 125000000304 alkynyl group Chemical group 0.000 claims abstract description 10
- 150000001732 carboxylic acid derivatives Chemical class 0.000 claims abstract description 6
- 150000004820 halides Chemical class 0.000 claims abstract description 6
- 125000000852 azido group Chemical group *N=[N+]=[N-] 0.000 claims abstract description 5
- 229910019142 PO4 Inorganic materials 0.000 claims abstract description 4
- 150000004649 carbonic acid derivatives Chemical class 0.000 claims abstract description 4
- 239000010452 phosphate Substances 0.000 claims abstract description 4
- 125000000467 secondary amino group Chemical group [H]N([*:1])[*:2] 0.000 claims abstract description 4
- 150000004657 carbamic acid derivatives Chemical class 0.000 claims abstract description 3
- 150000003467 sulfuric acid derivatives Chemical class 0.000 claims abstract description 3
- 125000002467 phosphate group Chemical class [H]OP(=O)(O[H])O[*] 0.000 claims abstract 2
- 125000001273 sulfonato group Chemical class [O-]S(*)(=O)=O 0.000 claims abstract 2
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 49
- 239000003960 organic solvent Substances 0.000 claims description 33
- RTZKZFJDLAIYFH-UHFFFAOYSA-N ether Substances CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 26
- -1 isopropionyl Chemical group 0.000 claims description 24
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 21
- 238000006243 chemical reaction Methods 0.000 claims description 21
- 125000006239 protecting group Chemical group 0.000 claims description 21
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical group ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 18
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 claims description 16
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 15
- 239000007864 aqueous solution Substances 0.000 claims description 15
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 claims description 14
- 229910052799 carbon Inorganic materials 0.000 claims description 14
- 239000003054 catalyst Substances 0.000 claims description 14
- 239000002904 solvent Substances 0.000 claims description 13
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Natural products CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 12
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 claims description 12
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 claims description 12
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 12
- 150000001338 aliphatic hydrocarbons Chemical class 0.000 claims description 12
- 239000000376 reactant Substances 0.000 claims description 11
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 10
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 claims description 8
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 claims description 8
- BDAGIHXWWSANSR-UHFFFAOYSA-M Formate Chemical compound [O-]C=O BDAGIHXWWSANSR-UHFFFAOYSA-M 0.000 claims description 8
- BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 claims description 8
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 8
- DTQVDTLACAAQTR-UHFFFAOYSA-M Trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-M 0.000 claims description 8
- 235000019270 ammonium chloride Nutrition 0.000 claims description 8
- DKPFZGUDAPQIHT-UHFFFAOYSA-N butyl acetate Chemical compound CCCCOC(C)=O DKPFZGUDAPQIHT-UHFFFAOYSA-N 0.000 claims description 8
- 239000012351 deprotecting agent Substances 0.000 claims description 7
- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 claims description 7
- 238000001914 filtration Methods 0.000 claims description 7
- 239000002253 acid Substances 0.000 claims description 6
- 150000003863 ammonium salts Chemical class 0.000 claims description 6
- 150000004945 aromatic hydrocarbons Chemical class 0.000 claims description 6
- 235000010323 ascorbic acid Nutrition 0.000 claims description 6
- 239000011668 ascorbic acid Substances 0.000 claims description 6
- 239000003638 chemical reducing agent Substances 0.000 claims description 6
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 6
- 150000002762 monocarboxylic acid derivatives Chemical class 0.000 claims description 6
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 claims description 6
- 239000012074 organic phase Substances 0.000 claims description 6
- FERIUCNNQQJTOY-UHFFFAOYSA-N Butyric acid Chemical compound CCCC(O)=O FERIUCNNQQJTOY-UHFFFAOYSA-N 0.000 claims description 5
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 claims description 5
- CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 claims description 5
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 claims description 5
- 235000011054 acetic acid Nutrition 0.000 claims description 5
- 150000001298 alcohols Chemical class 0.000 claims description 5
- 150000001768 cations Chemical class 0.000 claims description 5
- 150000002148 esters Chemical class 0.000 claims description 5
- 150000002576 ketones Chemical class 0.000 claims description 5
- 229910052751 metal Inorganic materials 0.000 claims description 5
- 239000002184 metal Substances 0.000 claims description 5
- 235000019260 propionic acid Nutrition 0.000 claims description 5
- JVBXVOWTABLYPX-UHFFFAOYSA-L sodium dithionite Chemical group [Na+].[Na+].[O-]S(=O)S([O-])=O JVBXVOWTABLYPX-UHFFFAOYSA-L 0.000 claims description 5
- VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 claims description 5
- SYBYTAAJFKOIEJ-UHFFFAOYSA-N 3-Methylbutan-2-one Chemical compound CC(C)C(C)=O SYBYTAAJFKOIEJ-UHFFFAOYSA-N 0.000 claims description 4
- USFZMSVCRYTOJT-UHFFFAOYSA-N Ammonium acetate Chemical compound N.CC(O)=O USFZMSVCRYTOJT-UHFFFAOYSA-N 0.000 claims description 4
- 239000005695 Ammonium acetate Substances 0.000 claims description 4
- ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 claims description 4
- YNQLUTRBYVCPMQ-UHFFFAOYSA-N Ethylbenzene Chemical compound CCC1=CC=CC=C1 YNQLUTRBYVCPMQ-UHFFFAOYSA-N 0.000 claims description 4
- JVTAAEKCZFNVCJ-UHFFFAOYSA-M Lactate Chemical compound CC(O)C([O-])=O JVTAAEKCZFNVCJ-UHFFFAOYSA-M 0.000 claims description 4
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 claims description 4
- OFBQJSOFQDEBGM-UHFFFAOYSA-N Pentane Chemical compound CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 claims description 4
- 150000001242 acetic acid derivatives Chemical class 0.000 claims description 4
- 235000019257 ammonium acetate Nutrition 0.000 claims description 4
- 229940043376 ammonium acetate Drugs 0.000 claims description 4
- 239000008346 aqueous phase Substances 0.000 claims description 4
- 229940072107 ascorbate Drugs 0.000 claims description 4
- 229940009098 aspartate Drugs 0.000 claims description 4
- YCNIBOIOWCTRCL-UHFFFAOYSA-N azane;2,2,2-trifluoroacetic acid Chemical compound [NH4+].[O-]C(=O)C(F)(F)F YCNIBOIOWCTRCL-UHFFFAOYSA-N 0.000 claims description 4
- 229930195712 glutamate Natural products 0.000 claims description 4
- 229940049906 glutamate Drugs 0.000 claims description 4
- 238000000227 grinding Methods 0.000 claims description 4
- 229940001447 lactate Drugs 0.000 claims description 4
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 claims description 4
- YKYONYBAUNKHLG-UHFFFAOYSA-N propyl acetate Chemical compound CCCOC(C)=O YKYONYBAUNKHLG-UHFFFAOYSA-N 0.000 claims description 4
- 239000003586 protic polar solvent Substances 0.000 claims description 4
- NUMQCACRALPSHD-UHFFFAOYSA-N tert-butyl ethyl ether Chemical compound CCOC(C)(C)C NUMQCACRALPSHD-UHFFFAOYSA-N 0.000 claims description 4
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 claims description 3
- XBDQKXXYIPTUBI-UHFFFAOYSA-M Propionate Chemical compound CCC([O-])=O XBDQKXXYIPTUBI-UHFFFAOYSA-M 0.000 claims description 3
- XSTXAVWGXDQKEL-UHFFFAOYSA-N Trichloroethylene Chemical group ClC=C(Cl)Cl XSTXAVWGXDQKEL-UHFFFAOYSA-N 0.000 claims description 3
- VZTDIZULWFCMLS-UHFFFAOYSA-N ammonium formate Chemical compound [NH4+].[O-]C=O VZTDIZULWFCMLS-UHFFFAOYSA-N 0.000 claims description 3
- 150000002170 ethers Chemical class 0.000 claims description 3
- 229960003750 ethyl chloride Drugs 0.000 claims description 3
- DUWWHGPELOTTOE-UHFFFAOYSA-N n-(5-chloro-2,4-dimethoxyphenyl)-3-oxobutanamide Chemical class COC1=CC(OC)=C(NC(=O)CC(C)=O)C=C1Cl DUWWHGPELOTTOE-UHFFFAOYSA-N 0.000 claims description 3
- 229910052723 transition metal Inorganic materials 0.000 claims description 3
- 150000003624 transition metals Chemical class 0.000 claims description 3
- UBOXGVDOUJQMTN-UHFFFAOYSA-N trichloroethylene Natural products ClCC(Cl)Cl UBOXGVDOUJQMTN-UHFFFAOYSA-N 0.000 claims description 3
- 125000003821 2-(trimethylsilyl)ethoxymethyl group Chemical group [H]C([H])([H])[Si](C([H])([H])[H])(C([H])([H])[H])C([H])([H])C(OC([H])([H])[*])([H])[H] 0.000 claims description 2
- JWUJQDFVADABEY-UHFFFAOYSA-N 2-methyltetrahydrofuran Chemical compound CC1CCCO1 JWUJQDFVADABEY-UHFFFAOYSA-N 0.000 claims description 2
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 claims description 2
- 239000004251 Ammonium lactate Substances 0.000 claims description 2
- KXDHJXZQYSOELW-UHFFFAOYSA-N Carbamic acid Chemical class NC(O)=O KXDHJXZQYSOELW-UHFFFAOYSA-N 0.000 claims description 2
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 claims description 2
- KRHYYFGTRYWZRS-UHFFFAOYSA-M Fluoride anion Chemical compound [F-] KRHYYFGTRYWZRS-UHFFFAOYSA-M 0.000 claims description 2
- NTIZESTWPVYFNL-UHFFFAOYSA-N Methyl isobutyl ketone Chemical compound CC(C)CC(C)=O NTIZESTWPVYFNL-UHFFFAOYSA-N 0.000 claims description 2
- UIHCLUNTQKBZGK-UHFFFAOYSA-N Methyl isobutyl ketone Natural products CCC(C)C(C)=O UIHCLUNTQKBZGK-UHFFFAOYSA-N 0.000 claims description 2
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 claims description 2
- RWRDLPDLKQPQOW-UHFFFAOYSA-O Pyrrolidinium ion Chemical class C1CC[NH2+]C1 RWRDLPDLKQPQOW-UHFFFAOYSA-O 0.000 claims description 2
- DHXVGJBLRPWPCS-UHFFFAOYSA-N Tetrahydropyran Chemical compound C1CCOCC1 DHXVGJBLRPWPCS-UHFFFAOYSA-N 0.000 claims description 2
- KXKVLQRXCPHEJC-UHFFFAOYSA-N acetic acid trimethyl ester Natural products COC(C)=O KXKVLQRXCPHEJC-UHFFFAOYSA-N 0.000 claims description 2
- 229940059265 ammonium lactate Drugs 0.000 claims description 2
- 235000019286 ammonium lactate Nutrition 0.000 claims description 2
- 239000000010 aprotic solvent Substances 0.000 claims description 2
- 229960005070 ascorbic acid Drugs 0.000 claims description 2
- QKWNIOMGXBERHJ-RXSVEWSESA-N azane;(2r)-2-[(1s)-1,2-dihydroxyethyl]-3,4-dihydroxy-2h-furan-5-one Chemical compound N.OC[C@H](O)[C@H]1OC(=O)C(O)=C1O QKWNIOMGXBERHJ-RXSVEWSESA-N 0.000 claims description 2
- RZOBLYBZQXQGFY-HSHFZTNMSA-N azanium;(2r)-2-hydroxypropanoate Chemical compound [NH4+].C[C@@H](O)C([O-])=O RZOBLYBZQXQGFY-HSHFZTNMSA-N 0.000 claims description 2
- PHKGGXPMPXXISP-DFWYDOINSA-N azanium;(4s)-4-amino-5-hydroxy-5-oxopentanoate Chemical compound [NH4+].[O-]C(=O)[C@@H]([NH3+])CCC([O-])=O PHKGGXPMPXXISP-DFWYDOINSA-N 0.000 claims description 2
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 2
- AQEFLFZSWDEAIP-UHFFFAOYSA-N di-tert-butyl ether Chemical compound CC(C)(C)OC(C)(C)C AQEFLFZSWDEAIP-UHFFFAOYSA-N 0.000 claims description 2
- YEOCBTKAGVNPMO-JIZZDEOASA-N diazanium;(2s)-2-aminobutanedioate Chemical compound [NH4+].[NH4+].[O-]C(=O)[C@@H](N)CC([O-])=O YEOCBTKAGVNPMO-JIZZDEOASA-N 0.000 claims description 2
- 150000001991 dicarboxylic acids Chemical class 0.000 claims description 2
- NKDDWNXOKDWJAK-UHFFFAOYSA-N dimethoxymethane Chemical compound COCOC NKDDWNXOKDWJAK-UHFFFAOYSA-N 0.000 claims description 2
- 235000019253 formic acid Nutrition 0.000 claims description 2
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 claims description 2
- 150000004693 imidazolium salts Chemical class 0.000 claims description 2
- GJRQTCIYDGXPES-UHFFFAOYSA-N iso-butyl acetate Natural products CC(C)COC(C)=O GJRQTCIYDGXPES-UHFFFAOYSA-N 0.000 claims description 2
- FGKJLKRYENPLQH-UHFFFAOYSA-M isocaproate Chemical compound CC(C)CCC([O-])=O FGKJLKRYENPLQH-UHFFFAOYSA-M 0.000 claims description 2
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 2
- OQAGVSWESNCJJT-UHFFFAOYSA-N isovaleric acid methyl ester Natural products COC(=O)CC(C)C OQAGVSWESNCJJT-UHFFFAOYSA-N 0.000 claims description 2
- 125000004184 methoxymethyl group Chemical group [H]C([H])([H])OC([H])([H])* 0.000 claims description 2
- 235000013917 monoammonium glutamate Nutrition 0.000 claims description 2
- 125000001501 propionyl group Chemical group O=C([*])C([H])([H])C([H])([H])[H] 0.000 claims description 2
- JUJWROOIHBZHMG-UHFFFAOYSA-O pyridinium Chemical class C1=CC=[NH+]C=C1 JUJWROOIHBZHMG-UHFFFAOYSA-O 0.000 claims description 2
- IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 claims description 2
- 239000012279 sodium borohydride Substances 0.000 claims description 2
- 229910000033 sodium borohydride Inorganic materials 0.000 claims description 2
- 125000001981 tert-butyldimethylsilyl group Chemical group [H]C([H])([H])[Si]([H])(C([H])([H])[H])[*]C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 2
- 125000000037 tert-butyldiphenylsilyl group Chemical group [H]C1=C([H])C([H])=C([H])C([H])=C1[Si]([H])([*]C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 claims description 2
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 2
- 125000001425 triazolyl group Chemical group 0.000 claims description 2
- 125000000025 triisopropylsilyl group Chemical group C(C)(C)[Si](C(C)C)(C(C)C)* 0.000 claims description 2
- 125000000026 trimethylsilyl group Chemical group [H]C([H])([H])[Si]([*])(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 2
- 239000008096 xylene Substances 0.000 claims description 2
- 125000000218 acetic acid group Chemical group C(C)(=O)* 0.000 claims 9
- 238000002360 preparation method Methods 0.000 description 23
- 125000004432 carbon atom Chemical group C* 0.000 description 15
- ITMCEJHCFYSIIV-UHFFFAOYSA-M triflate Chemical compound [O-]S(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-M 0.000 description 14
- 238000005160 1H NMR spectroscopy Methods 0.000 description 12
- MAKBMGXNXXXBFE-TURQNECASA-N 1-(beta-D-ribofuranosyl)-1,4-dihydronicotinamide Chemical compound C1=CCC(C(=O)N)=CN1[C@H]1[C@H](O)[C@H](O)[C@@H](CO)O1 MAKBMGXNXXXBFE-TURQNECASA-N 0.000 description 11
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 10
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 9
- 229910000831 Steel Inorganic materials 0.000 description 8
- 150000003841 chloride salts Chemical class 0.000 description 8
- 239000010959 steel Substances 0.000 description 8
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 7
- 125000004433 nitrogen atom Chemical group N* 0.000 description 7
- 150000008223 ribosides Chemical class 0.000 description 7
- 239000000243 solution Substances 0.000 description 7
- YNGDWRXWKFWCJY-UHFFFAOYSA-N 1,4-Dihydropyridine Chemical compound C1C=CNC=C1 YNGDWRXWKFWCJY-UHFFFAOYSA-N 0.000 description 6
- XBLVHTDFJBKJLG-UHFFFAOYSA-N Ethyl nicotinate Chemical compound CCOC(=O)C1=CC=CN=C1 XBLVHTDFJBKJLG-UHFFFAOYSA-N 0.000 description 6
- DFPAKSUCGFBDDF-UHFFFAOYSA-N Nicotinamide Chemical compound NC(=O)C1=CC=CN=C1 DFPAKSUCGFBDDF-UHFFFAOYSA-N 0.000 description 6
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 6
- 229940064982 ethylnicotinate Drugs 0.000 description 6
- 150000002500 ions Chemical class 0.000 description 6
- 230000007935 neutral effect Effects 0.000 description 6
- 238000000746 purification Methods 0.000 description 6
- 239000012429 reaction media Substances 0.000 description 6
- FTVLMFQEYACZNP-UHFFFAOYSA-N trimethylsilyl trifluoromethanesulfonate Chemical compound C[Si](C)(C)OS(=O)(=O)C(F)(F)F FTVLMFQEYACZNP-UHFFFAOYSA-N 0.000 description 6
- 238000000498 ball milling Methods 0.000 description 5
- 235000015872 dietary supplement Nutrition 0.000 description 5
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 5
- 230000009467 reduction Effects 0.000 description 5
- 150000003839 salts Chemical class 0.000 description 5
- 239000007858 starting material Substances 0.000 description 5
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 4
- DAYLJWODMCOQEW-TURQNECASA-N NMN zwitterion Chemical compound NC(=O)C1=CC=C[N+]([C@H]2[C@@H]([C@H](O)[C@@H](COP(O)([O-])=O)O2)O)=C1 DAYLJWODMCOQEW-TURQNECASA-N 0.000 description 4
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 4
- MJOQJPYNENPSSS-XQHKEYJVSA-N [(3r,4s,5r,6s)-4,5,6-triacetyloxyoxan-3-yl] acetate Chemical compound CC(=O)O[C@@H]1CO[C@@H](OC(C)=O)[C@H](OC(C)=O)[C@H]1OC(C)=O MJOQJPYNENPSSS-XQHKEYJVSA-N 0.000 description 4
- 239000000463 material Substances 0.000 description 4
- 239000011570 nicotinamide Substances 0.000 description 4
- 229960003966 nicotinamide Drugs 0.000 description 4
- JOUIQRNQJGXQDC-ZYUZMQFOSA-L nicotinate D-ribonucleotide(2-) Chemical compound O1[C@H](COP([O-])([O-])=O)[C@@H](O)[C@@H](O)[C@@H]1[N+]1=CC=CC(C([O-])=O)=C1 JOUIQRNQJGXQDC-ZYUZMQFOSA-L 0.000 description 4
- 230000003647 oxidation Effects 0.000 description 4
- 238000007254 oxidation reaction Methods 0.000 description 4
- 125000002827 triflate group Chemical class FC(S(=O)(=O)O*)(F)F 0.000 description 4
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 3
- 238000004293 19F NMR spectroscopy Methods 0.000 description 3
- HMFHBZSHGGEWLO-SOOFDHNKSA-N D-ribofuranose Chemical compound OC[C@H]1OC(O)[C@H](O)[C@@H]1O HMFHBZSHGGEWLO-SOOFDHNKSA-N 0.000 description 3
- PUEDDPCUCPRQNY-ZYUZMQFOSA-N D-ribosylnicotinate Chemical compound O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1[N+]1=CC=CC(C([O-])=O)=C1 PUEDDPCUCPRQNY-ZYUZMQFOSA-N 0.000 description 3
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 3
- PYMYPHUHKUWMLA-LMVFSUKVSA-N Ribose Natural products OC[C@@H](O)[C@@H](O)[C@@H](O)C=O PYMYPHUHKUWMLA-LMVFSUKVSA-N 0.000 description 3
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 3
- 159000000021 acetate salts Chemical class 0.000 description 3
- HMFHBZSHGGEWLO-UHFFFAOYSA-N alpha-D-Furanose-Ribose Natural products OCC1OC(O)C(O)C1O HMFHBZSHGGEWLO-UHFFFAOYSA-N 0.000 description 3
- 125000004122 cyclic group Chemical group 0.000 description 3
- 238000010511 deprotection reaction Methods 0.000 description 3
- VFRSADQPWYCXDG-LEUCUCNGSA-N ethyl (2s,5s)-5-methylpyrrolidine-2-carboxylate;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.CCOC(=O)[C@@H]1CC[C@H](C)N1 VFRSADQPWYCXDG-LEUCUCNGSA-N 0.000 description 3
- 150000004675 formic acid derivatives Chemical class 0.000 description 3
- GWYFCOCPABKNJV-UHFFFAOYSA-N isovaleric acid Chemical compound CC(C)CC(O)=O GWYFCOCPABKNJV-UHFFFAOYSA-N 0.000 description 3
- 235000014655 lactic acid Nutrition 0.000 description 3
- 239000010410 layer Substances 0.000 description 3
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 3
- 235000005152 nicotinamide Nutrition 0.000 description 3
- 239000000047 product Substances 0.000 description 3
- 235000017557 sodium bicarbonate Nutrition 0.000 description 3
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 3
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 2
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 2
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 2
- QXHYLZYIWRGUSD-UHFFFAOYSA-N C(C)(=O)C1=C(NC(=C(C(=O)N)C1)C(C)=O)C(C)=O Chemical compound C(C)(=O)C1=C(NC(=C(C(=O)N)C1)C(C)=O)C(C)=O QXHYLZYIWRGUSD-UHFFFAOYSA-N 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- BAWFJGJZGIEFAR-NNYOXOHSSA-O NAD(+) Chemical class NC(=O)C1=CC=C[N+]([C@H]2[C@@H]([C@H](O)[C@@H](COP(O)(=O)OP(O)(=O)OC[C@@H]3[C@H]([C@@H](O)[C@@H](O3)N3C4=NC=NC(N)=C4N=C3)O)O2)O)=C1 BAWFJGJZGIEFAR-NNYOXOHSSA-O 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical group C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
- 125000003282 alkyl amino group Chemical group 0.000 description 2
- 239000011203 carbon fibre reinforced carbon Substances 0.000 description 2
- 229950005499 carbon tetrachloride Drugs 0.000 description 2
- 229960001701 chloroform Drugs 0.000 description 2
- 125000004663 dialkyl amino group Chemical group 0.000 description 2
- 238000000605 extraction Methods 0.000 description 2
- 238000004108 freeze drying Methods 0.000 description 2
- 125000001072 heteroaryl group Chemical group 0.000 description 2
- 239000004310 lactic acid Substances 0.000 description 2
- 238000004811 liquid chromatography Methods 0.000 description 2
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 2
- 235000019341 magnesium sulphate Nutrition 0.000 description 2
- 239000000203 mixture Substances 0.000 description 2
- 235000001968 nicotinic acid Nutrition 0.000 description 2
- 239000011664 nicotinic acid Substances 0.000 description 2
- BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 description 2
- 239000011541 reaction mixture Substances 0.000 description 2
- 229920006395 saturated elastomer Polymers 0.000 description 2
- 239000007787 solid Substances 0.000 description 2
- 230000000707 stereoselective effect Effects 0.000 description 2
- 238000003756 stirring Methods 0.000 description 2
- 125000001424 substituent group Chemical group 0.000 description 2
- 150000003871 sulfonates Chemical class 0.000 description 2
- 238000010626 work up procedure Methods 0.000 description 2
- UOCLXMDMGBRAIB-UHFFFAOYSA-N 1,1,1-trichloroethane Chemical compound CC(Cl)(Cl)Cl UOCLXMDMGBRAIB-UHFFFAOYSA-N 0.000 description 1
- QIONYIKHPASLHO-UHFFFAOYSA-M 2,2,2-tribromoacetate Chemical compound [O-]C(=O)C(Br)(Br)Br QIONYIKHPASLHO-UHFFFAOYSA-M 0.000 description 1
- UTQNKKSJPHTPBS-UHFFFAOYSA-N 2,2,2-trichloroethanone Chemical group ClC(Cl)(Cl)[C]=O UTQNKKSJPHTPBS-UHFFFAOYSA-N 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-M Bicarbonate Chemical compound OC([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-M 0.000 description 1
- FERIUCNNQQJTOY-UHFFFAOYSA-M Butyrate Chemical compound CCCC([O-])=O FERIUCNNQQJTOY-UHFFFAOYSA-M 0.000 description 1
- WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 description 1
- 239000005909 Kieselgur Substances 0.000 description 1
- 241000699670 Mus sp. Species 0.000 description 1
- 238000005481 NMR spectroscopy Methods 0.000 description 1
- 208000008589 Obesity Diseases 0.000 description 1
- KJTLSVCANCCWHF-UHFFFAOYSA-N Ruthenium Chemical compound [Ru] KJTLSVCANCCWHF-UHFFFAOYSA-N 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 1
- 229940022663 acetate Drugs 0.000 description 1
- 125000004947 alkyl aryl amino group Chemical group 0.000 description 1
- 125000002877 alkyl aryl group Chemical group 0.000 description 1
- 125000004448 alkyl carbonyl group Chemical group 0.000 description 1
- 150000001356 alkyl thiols Chemical class 0.000 description 1
- HSFWRNGVRCDJHI-UHFFFAOYSA-N alpha-acetylene Natural products C#C HSFWRNGVRCDJHI-UHFFFAOYSA-N 0.000 description 1
- PNEYBMLMFCGWSK-UHFFFAOYSA-N aluminium oxide Inorganic materials [O-2].[O-2].[O-2].[Al+3].[Al+3] PNEYBMLMFCGWSK-UHFFFAOYSA-N 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 229910052786 argon Inorganic materials 0.000 description 1
- 125000001769 aryl amino group Chemical group 0.000 description 1
- 125000005129 aryl carbonyl group Chemical group 0.000 description 1
- 150000008378 aryl ethers Chemical group 0.000 description 1
- 150000001504 aryl thiols Chemical class 0.000 description 1
- 235000003704 aspartic acid Nutrition 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 1
- OQFSQFPPLPISGP-UHFFFAOYSA-N beta-carboxyaspartic acid Natural products OC(=O)C(N)C(C(O)=O)C(O)=O OQFSQFPPLPISGP-UHFFFAOYSA-N 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 230000002051 biphasic effect Effects 0.000 description 1
- 230000005587 bubbling Effects 0.000 description 1
- 125000004369 butenyl group Chemical group C(=CCC)* 0.000 description 1
- 125000000480 butynyl group Chemical group [*]C#CC([H])([H])C([H])([H])[H] 0.000 description 1
- 239000006227 byproduct Substances 0.000 description 1
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 1
- 150000007942 carboxylates Chemical class 0.000 description 1
- 238000009903 catalytic hydrogenation reaction Methods 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 125000004093 cyano group Chemical group *C#N 0.000 description 1
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 1
- 238000000354 decomposition reaction Methods 0.000 description 1
- 125000004986 diarylamino group Chemical group 0.000 description 1
- BSXZJWHTFAEYDT-UHFFFAOYSA-N diazanium diformate Chemical compound [NH4+].[NH4+].[O-]C=O.[O-]C=O BSXZJWHTFAEYDT-UHFFFAOYSA-N 0.000 description 1
- 239000002037 dichloromethane fraction Substances 0.000 description 1
- KPUWHANPEXNPJT-UHFFFAOYSA-N disiloxane Chemical class [SiH3]O[SiH3] KPUWHANPEXNPJT-UHFFFAOYSA-N 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 125000002534 ethynyl group Chemical group [H]C#C* 0.000 description 1
- 238000005111 flow chemistry technique Methods 0.000 description 1
- 235000013922 glutamic acid Nutrition 0.000 description 1
- 239000004220 glutamic acid Substances 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 239000010439 graphite Substances 0.000 description 1
- 229910002804 graphite Inorganic materials 0.000 description 1
- 230000007407 health benefit Effects 0.000 description 1
- FFUAGWLWBBFQJT-UHFFFAOYSA-N hexamethyldisilazane Chemical compound C[Si](C)(C)N[Si](C)(C)C FFUAGWLWBBFQJT-UHFFFAOYSA-N 0.000 description 1
- 235000009200 high fat diet Nutrition 0.000 description 1
- 238000004128 high performance liquid chromatography Methods 0.000 description 1
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- 229910052741 iridium Inorganic materials 0.000 description 1
- GKOZUEZYRPOHIO-UHFFFAOYSA-N iridium atom Chemical compound [Ir] GKOZUEZYRPOHIO-UHFFFAOYSA-N 0.000 description 1
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
- 125000004491 isohexyl group Chemical group C(CCC(C)C)* 0.000 description 1
- 125000001972 isopentyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])C([H])([H])* 0.000 description 1
- JMMWKPVZQRWMSS-UHFFFAOYSA-N isopropanol acetate Natural products CC(C)OC(C)=O JMMWKPVZQRWMSS-UHFFFAOYSA-N 0.000 description 1
- 229940011051 isopropyl acetate Drugs 0.000 description 1
- 238000011031 large-scale manufacturing process Methods 0.000 description 1
- 150000002739 metals Chemical class 0.000 description 1
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 1
- 230000005012 migration Effects 0.000 description 1
- 238000013508 migration Methods 0.000 description 1
- 125000002950 monocyclic group Chemical group 0.000 description 1
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000001280 n-hexyl group Chemical group C(CCCCC)* 0.000 description 1
- 125000000740 n-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 229950006238 nadide Drugs 0.000 description 1
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 1
- 229910000069 nitrogen hydride Inorganic materials 0.000 description 1
- 235000020824 obesity Nutrition 0.000 description 1
- 150000007530 organic bases Chemical class 0.000 description 1
- 239000012044 organic layer Substances 0.000 description 1
- 229910052762 osmium Inorganic materials 0.000 description 1
- SYQBFIAQOQZEGI-UHFFFAOYSA-N osmium atom Chemical compound [Os] SYQBFIAQOQZEGI-UHFFFAOYSA-N 0.000 description 1
- 230000004783 oxidative metabolism Effects 0.000 description 1
- 229910052763 palladium Inorganic materials 0.000 description 1
- 239000008188 pellet Substances 0.000 description 1
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- XYFCBTPGUUZFHI-UHFFFAOYSA-O phosphonium Chemical compound [PH4+] XYFCBTPGUUZFHI-UHFFFAOYSA-O 0.000 description 1
- 150000003013 phosphoric acid derivatives Chemical class 0.000 description 1
- 229910052697 platinum Inorganic materials 0.000 description 1
- 125000003367 polycyclic group Chemical group 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 1
- 125000004368 propenyl group Chemical group C(=CC)* 0.000 description 1
- 125000002568 propynyl group Chemical group [*]C#CC([H])([H])[H] 0.000 description 1
- 235000018102 proteins Nutrition 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 230000035484 reaction time Effects 0.000 description 1
- 238000009877 rendering Methods 0.000 description 1
- 238000004366 reverse phase liquid chromatography Methods 0.000 description 1
- 229910052703 rhodium Inorganic materials 0.000 description 1
- 239000010948 rhodium Substances 0.000 description 1
- MHOVAHRLVXNVSD-UHFFFAOYSA-N rhodium atom Chemical compound [Rh] MHOVAHRLVXNVSD-UHFFFAOYSA-N 0.000 description 1
- 238000002390 rotary evaporation Methods 0.000 description 1
- 229910052707 ruthenium Inorganic materials 0.000 description 1
- 239000000377 silicon dioxide Substances 0.000 description 1
- 235000017550 sodium carbonate Nutrition 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- 238000000527 sonication Methods 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 239000001117 sulphuric acid Substances 0.000 description 1
- 235000011149 sulphuric acid Nutrition 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- FPGGTKZVZWFYPV-UHFFFAOYSA-M tetrabutylammonium fluoride Chemical compound [F-].CCCC[N+](CCCC)(CCCC)CCCC FPGGTKZVZWFYPV-UHFFFAOYSA-M 0.000 description 1
- 150000003573 thiols Chemical class 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- DNUYPCSVTPIXRE-UHFFFAOYSA-N tribromomethanesulfonic acid Chemical compound OS(=O)(=O)C(Br)(Br)Br DNUYPCSVTPIXRE-UHFFFAOYSA-N 0.000 description 1
- 229940066528 trichloroacetate Drugs 0.000 description 1
- YNJBWRMUSHSURL-UHFFFAOYSA-N trichloroacetic acid Chemical compound OC(=O)C(Cl)(Cl)Cl YNJBWRMUSHSURL-UHFFFAOYSA-N 0.000 description 1
- VYGSFTVYZHNGBU-UHFFFAOYSA-N trichloromethanesulfonic acid Chemical compound OS(=O)(=O)C(Cl)(Cl)Cl VYGSFTVYZHNGBU-UHFFFAOYSA-N 0.000 description 1
- 125000004044 trifluoroacetyl group Chemical group FC(C(=O)*)(F)F 0.000 description 1
- APOOWQWYEKRGKA-UHFFFAOYSA-N trimethylsilyl n-trimethylsilylpyridine-3-carboximidate Chemical compound C[Si](C)(C)OC(=N[Si](C)(C)C)C1=CC=CN=C1 APOOWQWYEKRGKA-UHFFFAOYSA-N 0.000 description 1
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H19/00—Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof
- C07H19/02—Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof sharing nitrogen
- C07H19/04—Heterocyclic radicals containing only nitrogen atoms as ring hetero atom
- C07H19/048—Pyridine radicals
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23L—FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES, NOT OTHERWISE PROVIDED FOR; PREPARATION OR TREATMENT THEREOF
- A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
- A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H1/00—Processes for the preparation of sugar derivatives
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H1/00—Processes for the preparation of sugar derivatives
- C07H1/06—Separation; Purification
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H19/00—Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof
- C07H19/02—Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof sharing nitrogen
- C07H19/04—Heterocyclic radicals containing only nitrogen atoms as ring hetero atom
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P20/00—Technologies relating to chemical industry
- Y02P20/50—Improvements relating to the production of bulk chemicals
- Y02P20/55—Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P20/00—Technologies relating to chemical industry
- Y02P20/50—Improvements relating to the production of bulk chemicals
- Y02P20/582—Recycling of unreacted starting or intermediate materials
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Molecular Biology (AREA)
- General Health & Medical Sciences (AREA)
- Genetics & Genomics (AREA)
- Biotechnology (AREA)
- Biochemistry (AREA)
- Mycology (AREA)
- Nutrition Science (AREA)
- Food Science & Technology (AREA)
- Polymers & Plastics (AREA)
- Saccharide Compounds (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Pyridine Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CA3192957A CA3192957A1 (en) | 2013-07-29 | 2014-07-24 | Methods of preparing nicotinamide riboside and derivatives thereof |
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GBGB1313465.5A GB201313465D0 (en) | 2013-07-29 | 2013-07-29 | Methods of preparing nicotinamide riboside and derivatives thereof |
| GB1313465.5 | 2013-07-29 | ||
| PCT/EP2014/065971 WO2015014722A1 (en) | 2013-07-29 | 2014-07-24 | Methods of preparing nicotinamide riboside and derivatives thereof |
Related Child Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA3192957A Division CA3192957A1 (en) | 2013-07-29 | 2014-07-24 | Methods of preparing nicotinamide riboside and derivatives thereof |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CA2918955A1 CA2918955A1 (en) | 2015-02-05 |
| CA2918955C true CA2918955C (en) | 2023-05-09 |
Family
ID=49167061
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA3192957A Pending CA3192957A1 (en) | 2013-07-29 | 2014-07-24 | Methods of preparing nicotinamide riboside and derivatives thereof |
| CA2918955A Active CA2918955C (en) | 2013-07-29 | 2014-07-24 | Methods of preparing nicotinamide riboside and derivatives thereof |
Family Applications Before (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA3192957A Pending CA3192957A1 (en) | 2013-07-29 | 2014-07-24 | Methods of preparing nicotinamide riboside and derivatives thereof |
Country Status (14)
| Country | Link |
|---|---|
| US (6) | US10000519B2 (enExample) |
| EP (2) | EP3027635B1 (enExample) |
| JP (1) | JP6208352B2 (enExample) |
| KR (2) | KR102414886B1 (enExample) |
| CN (2) | CN105636973B (enExample) |
| AU (4) | AU2014298629B2 (enExample) |
| BR (1) | BR112016001774B1 (enExample) |
| CA (2) | CA3192957A1 (enExample) |
| ES (1) | ES2652654T3 (enExample) |
| GB (1) | GB201313465D0 (enExample) |
| HK (1) | HK1255037A1 (enExample) |
| MX (1) | MX349969B (enExample) |
| WO (1) | WO2015014722A1 (enExample) |
| ZA (1) | ZA201802315B (enExample) |
Families Citing this family (47)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB201313465D0 (en) | 2013-07-29 | 2013-09-11 | Queens University Of The Belfast | Methods of preparing nicotinamide riboside and derivatives thereof |
| US10316054B2 (en) | 2014-06-02 | 2019-06-11 | Glaxosmithkline Intellectual Property (No. 2) Limited | Preparation and use of crystalline beta-D-nicotinamide riboside |
| JP6559713B2 (ja) * | 2014-06-06 | 2019-08-14 | グラクソスミスクライン、インテレクチュアル、プロパティー、（ナンバー２）、リミテッドＧｌａｘｏｓｍｉｔｈｋｌｉｎｅ Ｉｎｔｅｌｌｅｃｔｕａｌ Ｐｒｏｐｅｒｔｙ （Ｎｏ．２） Ｌｉｍｉｔｅｄ | ニコチンアミドリボシド類似体ならびにその医薬組成物および使用 |
| CN106715454B (zh) * | 2014-07-24 | 2020-06-16 | 格雷斯公司 | 烟酰胺核苷的结晶形式 |
| FI3268379T3 (fi) * | 2015-03-09 | 2023-12-15 | Grace W R & Co | Nikotiiniamidiribosidin kiteinen muoto |
| BR112017019696A2 (pt) * | 2015-03-16 | 2018-09-04 | ChromaDex Inc. | composto e usos de um composto |
| WO2017011788A1 (en) | 2015-07-15 | 2017-01-19 | Cornell University | Syntheses, activities, and methods of use of dihydronicotinamide riboside derivatives |
| KR102354784B1 (ko) | 2015-08-05 | 2022-01-25 | 메트로 인터내셔널 바이오테크 엘엘씨 | 니코틴아미드 모노뉴클레오티드 유도체 및 그 용도 |
| GB2542881B (en) | 2015-10-02 | 2020-01-01 | Carr Andrew | Crystal forms of ß-nicotinamide mononucleotide |
| WO2017079195A1 (en) * | 2015-11-02 | 2017-05-11 | Mitobridge, Inc. | Nicotinamide riboside and nicotinamide mononucleotide derivatives for use in the treatments of mitochondrial-related diseases |
| WO2017145151A1 (en) | 2016-02-23 | 2017-08-31 | Yissum Research Development Company Of The Hebrew University Of Jerusalem Ltd. | Process for preparation of nicotinamide riboside (nr) and cosmetic composition comprising (nr and a phosphate-binding agent |
| AU2017232930B2 (en) | 2016-03-16 | 2021-03-25 | ChromaDex Inc. | B-vitamin and amino acid conjugates of nicotinoyl ribosides and reduced nicotinoyl ribosides, derivatives thereof, and methods of preparation thereof |
| NZ747693A (en) | 2016-04-20 | 2023-07-28 | Chromadex Inc | Use of nicotinic acid riboside or nicotinamide riboside derivatives, and reduced derivatives thereof, as nad+increasing precursors |
| WO2017218580A1 (en) | 2016-06-14 | 2017-12-21 | Rejuvenation Therapeutics Corporation | Synthetic methods for the preparation of nicotinamide riboside and related compounds |
| GB2553001A (en) * | 2016-08-19 | 2018-02-21 | The Queen's Univ Of Belfast | Lactone intermediates of nicotinamide riboside and nicotinate riboside |
| WO2018089830A1 (en) | 2016-11-11 | 2018-05-17 | The Queen's University Of Belfast | Efficient and scalable syntheses of nicotinoyl ribosides and reduced nicotinoyl ribosides, modified derivatives thereof, phosphorylated analogs thereof, adenylyl dinucleotide conjugates thereof, and novel crystalline forms thereof |
| BR112019010607B1 (pt) | 2016-11-29 | 2023-10-31 | University Of Iowa Research Foundation | Uso de precursores de nad e composição compreendendo os referidos precursores |
| US11071747B2 (en) | 2016-11-29 | 2021-07-27 | University Of Iowa Research Foundation | Use of NAD precursors for breast enhancement |
| EP3642214A2 (en) | 2017-06-19 | 2020-04-29 | Gangadhara Ganapati | Nicotinamide riboside derivatives and their uses |
| JP2020526511A (ja) * | 2017-06-30 | 2020-08-31 | エリジウム・ヘルス・インコーポレイテッド | ニコチンアミドリボシドの合成方法 |
| US11414407B2 (en) | 2017-12-22 | 2022-08-16 | Elysium Health, Inc. | Crystalline forms of nicotinamide riboside chloride |
| WO2019122084A1 (en) | 2017-12-22 | 2019-06-27 | Stemtek Therapeutics, S.L. | Process for the preparation of nicotinamide riboside chloride derivatives |
| WO2019152416A1 (en) | 2018-01-30 | 2019-08-08 | Metro International Biotech, Llc | Nicotinamide riboside analogs, pharmaceutical compositions, and uses thereof |
| CN110283221A (zh) * | 2018-03-19 | 2019-09-27 | 药源药物化学（上海）有限公司 | 杂环化合物的制备和纯化方法 |
| CN110452277A (zh) * | 2018-05-07 | 2019-11-15 | 明特奇点医疗科技(成都)有限公司 | 一种烟酰胺核糖的制备方法 |
| AU2019274524A1 (en) * | 2018-05-22 | 2021-01-07 | Roland Dolle | Amino acid salts of nicotinic acid ribosides as anti-aging agents |
| US20210267251A1 (en) * | 2018-06-21 | 2021-09-02 | Societe Des Produits Nestle S.A. | Compositions and methods using a nicotinamide adenine dinucleotide (nad+) precursor and at least one ketone or ketone precursor |
| CN108774278A (zh) * | 2018-09-10 | 2018-11-09 | 张洪喜 | 一种制备尼克酰胺核苷盐的方法 |
| KR102060374B1 (ko) * | 2018-12-14 | 2019-12-30 | 주식회사 휴메딕스 | 지방알코올 컨쥬게이션된 니코틴아미드 리보사이드 유도체 |
| US11833167B2 (en) | 2018-12-17 | 2023-12-05 | Mitopower Llc | Nicotinyl riboside compounds and their uses |
| US11939348B2 (en) | 2019-03-22 | 2024-03-26 | Metro International Biotech, Llc | Compositions comprising a phosphorus derivative of nicotinamide riboside and methods for modulation of nicotinamide adenine dinucleotide |
| US10618927B1 (en) | 2019-03-22 | 2020-04-14 | Metro International Biotech, Llc | Compositions and methods for modulation of nicotinamide adenine dinucleotide |
| CA3148300A1 (en) | 2019-07-19 | 2021-01-28 | Biosynth Ag | Method of making nicotinamide ribofuranoside salts, nicotinamide ribofuranoside salts as such, and uses thereof |
| WO2021030551A1 (en) * | 2019-08-14 | 2021-02-18 | Metro International Biotech, Llc | Compounds and compositions for differential modulation of nicotinamide adenine dinucleotide |
| CN110642897B (zh) * | 2019-09-27 | 2021-04-06 | 武汉一若生物材料有限公司 | 一种β-烟酰胺核糖氯化物的制备方法 |
| CN110658224B (zh) * | 2019-10-15 | 2022-11-22 | 中国中医科学院中药研究所 | 一种氢核磁定量分析技术测定nmn绝对含量的方法 |
| CN111153953A (zh) * | 2020-01-07 | 2020-05-15 | 杭州洁汉化工有限公司 | 一种烟酰胺核糖氯化物的高效合成方法 |
| CN111454311B (zh) * | 2020-04-03 | 2021-10-19 | 深圳市迪克曼科技开发有限公司 | 烟酰胺核糖的有机酸盐及其组合物与制备方法 |
| CN111647032B (zh) * | 2020-06-29 | 2023-02-24 | 上海舒泽生物科技研究所 | 一种β-烟酰胺单核苷酸的合成方法 |
| CN111848710A (zh) * | 2020-08-20 | 2020-10-30 | 深圳市迪克曼科技开发有限公司 | 烟酰胺核糖及其还原态、盐的制备方法 |
| WO2022058312A1 (en) * | 2020-09-15 | 2022-03-24 | Société des Produits Nestlé S.A. | Methods for producing dihydronicotinamide riboside from nicotinamide riboside chloride |
| CN112851730B (zh) * | 2021-01-08 | 2023-02-21 | 厦门瑞林药业有限公司 | 一种nmn中间体nr氯化物合成方法 |
| JP2024517260A (ja) | 2021-05-04 | 2024-04-19 | ボーハン アンド カンパニー エーエス | ニコチンアミドリボシドクロリド（ｎｒｃｌ）の合成プロセス |
| IL308577A (en) | 2021-05-27 | 2024-01-01 | Metro Int Biotech Llc | Crystalline solids of nicotinic acid mononucleotides and their esters and methods for their preparation and use |
| EP4486751A1 (en) | 2022-03-04 | 2025-01-08 | Bohan & Co AS. | Process for synthesis of 1,4-dihydronicotinamide riboside (nrh) from nicotinamide-beta-riboside triacetate chloride (nra-cl) |
| CN116462727A (zh) * | 2023-04-23 | 2023-07-21 | 安徽瑞邦生物科技有限公司 | 一种β-烟酰胺核糖氯化物的制备方法 |
| US20240415863A1 (en) * | 2023-06-14 | 2024-12-19 | ChromaDex Inc. | Nicotinamide riboside and derivatives thereof in intravenous formulations and methods of use thereof |
Family Cites Families (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1993008288A1 (en) * | 1991-10-23 | 1993-04-29 | Cancer Research Campaign Technology Limited | Bacterial nitroreductase for the reduction of cb 1954 and analogues thereof to a cytotoxic form |
| US6689760B1 (en) * | 2000-07-10 | 2004-02-10 | Enzrel Inc. | Anti-mycobacterial compositions |
| EP3369738B1 (en) * | 2005-11-18 | 2020-05-20 | Cornell Research Foundation, Inc. | Method for making nicotinoyl ribosides and nicotinamide beta-riboside |
| US9603862B2 (en) * | 2009-12-14 | 2017-03-28 | Cornell University | Activation and activators of SIRT5 |
| JP2013522171A (ja) * | 2010-03-01 | 2013-06-13 | ミレクシス， インコーポレイテッド | 化合物およびその治療用途 |
| GB201313465D0 (en) | 2013-07-29 | 2013-09-11 | Queens University Of The Belfast | Methods of preparing nicotinamide riboside and derivatives thereof |
| JP6559713B2 (ja) * | 2014-06-06 | 2019-08-14 | グラクソスミスクライン、インテレクチュアル、プロパティー、（ナンバー２）、リミテッドＧｌａｘｏｓｍｉｔｈｋｌｉｎｅ Ｉｎｔｅｌｌｅｃｔｕａｌ Ｐｒｏｐｅｒｔｙ （Ｎｏ．２） Ｌｉｍｉｔｅｄ | ニコチンアミドリボシド類似体ならびにその医薬組成物および使用 |
-
2013
- 2013-07-29 GB GBGB1313465.5A patent/GB201313465D0/en not_active Ceased
-
2014
- 2014-07-24 US US14/908,831 patent/US10000519B2/en active Active
- 2014-07-24 BR BR112016001774-9A patent/BR112016001774B1/pt active IP Right Grant
- 2014-07-24 EP EP14744082.0A patent/EP3027635B1/en active Active
- 2014-07-24 AU AU2014298629A patent/AU2014298629B2/en active Active
- 2014-07-24 WO PCT/EP2014/065971 patent/WO2015014722A1/en not_active Ceased
- 2014-07-24 MX MX2016001211A patent/MX349969B/es active IP Right Grant
- 2014-07-24 CN CN201480043268.1A patent/CN105636973B/zh active Active
- 2014-07-24 CA CA3192957A patent/CA3192957A1/en active Pending
- 2014-07-24 EP EP17191481.5A patent/EP3321274A1/en active Pending
- 2014-07-24 CA CA2918955A patent/CA2918955C/en active Active
- 2014-07-24 ES ES14744082.0T patent/ES2652654T3/es active Active
- 2014-07-24 CN CN201810413840.9A patent/CN108707174A/zh active Pending
- 2014-07-24 KR KR1020217009552A patent/KR102414886B1/ko active Active
- 2014-07-24 JP JP2016530446A patent/JP6208352B2/ja active Active
- 2014-07-24 KR KR1020167005556A patent/KR102303966B1/ko active Active
-
2018
- 2018-02-27 US US15/905,922 patent/US10815262B2/en active Active
- 2018-04-09 ZA ZA2018/02315A patent/ZA201802315B/en unknown
- 2018-08-01 AU AU2018211238A patent/AU2018211238A1/en not_active Abandoned
- 2018-11-06 HK HK18114160.5A patent/HK1255037A1/en unknown
-
2020
- 2020-02-21 AU AU2020201254A patent/AU2020201254B2/en active Active
- 2020-05-29 US US16/886,985 patent/US11584770B2/en active Active
-
2022
- 2022-05-04 US US17/736,834 patent/US11981698B2/en active Active
- 2022-05-12 AU AU2022203196A patent/AU2022203196B2/en active Active
-
2023
- 2023-04-26 US US18/307,733 patent/US12252506B2/en active Active
-
2024
- 2024-03-07 US US18/598,617 patent/US20240239831A1/en active Pending
Also Published As
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US12252506B2 (en) | Methods of preparing nicotinamide riboside and derivatives thereof | |
| HK1218918B (en) | Methods of preparing nicotinamide riboside and derivatives thereof | |
| CN101089008B (zh) | 虎眼万年青osw-1皂甙的无a、b环的双环类似物、合成方法和用途 | |
| NZ716277B2 (en) | Methods of preparing nicotinamide riboside and derivatives thereof | |
| JPH0633263B2 (ja) | ７−ヒドロキシグアニン誘導体及びその製造方法並びにそれを有効成分とする抗腫瘍剤 | |
| TAKAMURA et al. | Syntheses and antitumor activities of N6, N6-dimethyladenosine carboxylate analogues | |
| Kunig et al. | Enantiomerically pure 3-hydroxypropyl diisopropylidene mannose derivatives | |
| Kim et al. | Synthetic Studies Related to Ezomycins and Octosyl Acids: Synthesis of Heptofuranose Nucleosides | |
| JPS6259716B2 (enExample) | ||
| Boydell | The enantioselective synthesis of a [alpha], a [alpha], ́b [beta], b [beta]-́tetrafluoroethylidene substituted carbohydrates | |
| JPH09255697A (ja) | １０位置換ハイドロキシメチル１４員環マクロライド誘導体 | |
| JPWO1990015812A1 (ja) | ２―アルキニルアデノシンの合成中間体、該合成中間体の製造法、該合成中間体を利用した２―アルキニルアデノシンの製造法および安定な２―アルキニルアデノシン誘導体 |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| EEER | Examination request |
Effective date: 20190717 |
|
| EEER | Examination request |
Effective date: 20190717 |
|
| EEER | Examination request |
Effective date: 20190717 |
|
| EEER | Examination request |
Effective date: 20190717 |
|
| EEER | Examination request |
Effective date: 20190717 |
|
| EEER | Examination request |
Effective date: 20190717 |