JP2020033326A - Deodorant - Google Patents
Deodorant Download PDFInfo
- Publication number
- JP2020033326A JP2020033326A JP2018163456A JP2018163456A JP2020033326A JP 2020033326 A JP2020033326 A JP 2020033326A JP 2018163456 A JP2018163456 A JP 2018163456A JP 2018163456 A JP2018163456 A JP 2018163456A JP 2020033326 A JP2020033326 A JP 2020033326A
- Authority
- JP
- Japan
- Prior art keywords
- group
- ring
- formula
- body odor
- reaction
- 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.)
- Granted
Links
- 239000002781 deodorant agent Substances 0.000 title abstract 3
- 150000001875 compounds Chemical class 0.000 claims abstract description 69
- 208000035985 Body Odor Diseases 0.000 claims abstract description 54
- 206010040904 Skin odour abnormal Diseases 0.000 claims abstract description 54
- 125000001424 substituent group Chemical group 0.000 claims abstract description 24
- 150000003839 salts Chemical class 0.000 claims abstract description 23
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract description 16
- 239000004480 active ingredient Substances 0.000 claims abstract description 5
- 150000004677 hydrates Chemical class 0.000 claims abstract description 3
- 125000001931 aliphatic group Chemical group 0.000 claims description 21
- 125000005843 halogen group Chemical group 0.000 claims description 11
- 125000001183 hydrocarbyl group Chemical group 0.000 claims 1
- 230000000694 effects Effects 0.000 abstract description 12
- 230000002401 inhibitory effect Effects 0.000 abstract 1
- 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 64
- 108010024636 Glutathione Proteins 0.000 description 32
- 229960003180 glutathione Drugs 0.000 description 32
- 238000006243 chemical reaction Methods 0.000 description 31
- 238000000034 method Methods 0.000 description 24
- -1 -butyl group Chemical group 0.000 description 23
- 239000000126 substance Substances 0.000 description 23
- BSAIUMLZVGUGKX-UHFFFAOYSA-N 2-Nonenal Natural products CCCCCCC=CC=O BSAIUMLZVGUGKX-UHFFFAOYSA-N 0.000 description 19
- BSAIUMLZVGUGKX-FPLPWBNLSA-N 2-nonenal Chemical compound CCCCCC\C=C/C=O BSAIUMLZVGUGKX-FPLPWBNLSA-N 0.000 description 17
- 210000003491 skin Anatomy 0.000 description 16
- 239000002904 solvent Substances 0.000 description 15
- 125000004432 carbon atom Chemical group C* 0.000 description 13
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical class CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 12
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 11
- 238000004519 manufacturing process Methods 0.000 description 11
- 125000000217 alkyl group Chemical group 0.000 description 10
- 125000000623 heterocyclic group Chemical group 0.000 description 10
- 125000006239 protecting group Chemical group 0.000 description 10
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 9
- SJRJJKPEHAURKC-UHFFFAOYSA-N N-Methylmorpholine Chemical class CN1CCOCC1 SJRJJKPEHAURKC-UHFFFAOYSA-N 0.000 description 9
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical group C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 9
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 9
- 150000001299 aldehydes Chemical class 0.000 description 9
- 230000003287 optical effect Effects 0.000 description 9
- 125000002029 aromatic hydrocarbon group Chemical group 0.000 description 8
- 230000032683 aging Effects 0.000 description 7
- 210000001099 axilla Anatomy 0.000 description 7
- 239000002585 base Substances 0.000 description 7
- 125000004093 cyano group Chemical group *C#N 0.000 description 7
- 239000012351 deprotecting agent Substances 0.000 description 7
- PAMIQIKDUOTOBW-UHFFFAOYSA-N 1-methylpiperidine Chemical class CN1CCCCC1 PAMIQIKDUOTOBW-UHFFFAOYSA-N 0.000 description 6
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 6
- 241000894006 Bacteria Species 0.000 description 6
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 6
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 6
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 6
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 6
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 6
- 239000002253 acid Substances 0.000 description 6
- 125000003277 amino group Chemical group 0.000 description 6
- 125000003118 aryl group Chemical group 0.000 description 6
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 6
- 239000002537 cosmetic Substances 0.000 description 6
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 6
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Chemical class C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 6
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 6
- SECPZKHBENQXJG-FPLPWBNLSA-N palmitoleic acid Chemical compound CCCCCC\C=C/CCCCCCCC(O)=O SECPZKHBENQXJG-FPLPWBNLSA-N 0.000 description 6
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 6
- 238000007259 addition reaction Methods 0.000 description 5
- 125000003342 alkenyl group Chemical group 0.000 description 5
- 125000003545 alkoxy group Chemical group 0.000 description 5
- VSCWAEJMTAWNJL-UHFFFAOYSA-K aluminium trichloride Chemical compound Cl[Al](Cl)Cl VSCWAEJMTAWNJL-UHFFFAOYSA-K 0.000 description 5
- 210000004027 cell Anatomy 0.000 description 5
- 150000002430 hydrocarbons Chemical group 0.000 description 5
- 239000000203 mixture Substances 0.000 description 5
- 230000035484 reaction time Effects 0.000 description 5
- 238000003786 synthesis reaction Methods 0.000 description 5
- NWUYHJFMYQTDRP-UHFFFAOYSA-N 1,2-bis(ethenyl)benzene;1-ethenyl-2-ethylbenzene;styrene Chemical compound C=CC1=CC=CC=C1.CCC1=CC=CC=C1C=C.C=CC1=CC=CC=C1C=C NWUYHJFMYQTDRP-UHFFFAOYSA-N 0.000 description 4
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 4
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 4
- JLTDJTHDQAWBAV-UHFFFAOYSA-N N,N-dimethylaniline Chemical class CN(C)C1=CC=CC=C1 JLTDJTHDQAWBAV-UHFFFAOYSA-N 0.000 description 4
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 4
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 4
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical class C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 4
- SMWDFEZZVXVKRB-UHFFFAOYSA-N Quinoline Chemical class N1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-UHFFFAOYSA-N 0.000 description 4
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 4
- 125000002723 alicyclic group Chemical group 0.000 description 4
- 229910052783 alkali metal Inorganic materials 0.000 description 4
- 125000003710 aryl alkyl group Chemical group 0.000 description 4
- 125000004429 atom Chemical group 0.000 description 4
- 230000015572 biosynthetic process Effects 0.000 description 4
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 description 4
- 239000003054 catalyst Substances 0.000 description 4
- 239000007795 chemical reaction product Substances 0.000 description 4
- GHVNFZFCNZKVNT-UHFFFAOYSA-N decanoic acid Chemical compound CCCCCCCCCC(O)=O GHVNFZFCNZKVNT-UHFFFAOYSA-N 0.000 description 4
- 238000010511 deprotection reaction Methods 0.000 description 4
- FBUKVWPVBMHYJY-UHFFFAOYSA-N nonanoic acid Chemical compound CCCCCCCCC(O)=O FBUKVWPVBMHYJY-UHFFFAOYSA-N 0.000 description 4
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 4
- 230000001737 promoting effect Effects 0.000 description 4
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Chemical class COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 4
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 4
- GETQZCLCWQTVFV-UHFFFAOYSA-N trimethylamine Chemical class CN(C)C GETQZCLCWQTVFV-UHFFFAOYSA-N 0.000 description 4
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 3
- 235000021319 Palmitoleic acid Nutrition 0.000 description 3
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical group C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 3
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
- 230000003213 activating effect Effects 0.000 description 3
- 229910052799 carbon Inorganic materials 0.000 description 3
- 239000003795 chemical substances by application Substances 0.000 description 3
- SECPZKHBENQXJG-UHFFFAOYSA-N cis-palmitoleic acid Natural products CCCCCCC=CCCCCCCCC(O)=O SECPZKHBENQXJG-UHFFFAOYSA-N 0.000 description 3
- 238000012258 culturing Methods 0.000 description 3
- 235000014113 dietary fatty acids Nutrition 0.000 description 3
- 239000003814 drug Substances 0.000 description 3
- 210000001339 epidermal cell Anatomy 0.000 description 3
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 3
- 239000000194 fatty acid Substances 0.000 description 3
- 229930195729 fatty acid Natural products 0.000 description 3
- 150000004665 fatty acids Chemical class 0.000 description 3
- 238000002290 gas chromatography-mass spectrometry Methods 0.000 description 3
- 125000005842 heteroatom Chemical group 0.000 description 3
- 239000001257 hydrogen Substances 0.000 description 3
- 229910052739 hydrogen Inorganic materials 0.000 description 3
- 239000003112 inhibitor Substances 0.000 description 3
- 239000003456 ion exchange resin Substances 0.000 description 3
- 229920003303 ion-exchange polymer Polymers 0.000 description 3
- 230000014759 maintenance of location Effects 0.000 description 3
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 3
- 238000002360 preparation method Methods 0.000 description 3
- 230000028327 secretion Effects 0.000 description 3
- IMFACGCPASFAPR-UHFFFAOYSA-N tributylamine Chemical class CCCCN(CCCC)CCCC IMFACGCPASFAPR-UHFFFAOYSA-N 0.000 description 3
- 239000003021 water soluble solvent Substances 0.000 description 3
- XWHRTPLAQGGJDN-FPLPWBNLSA-N (z)-hexadec-9-eneperoxoic acid Chemical compound CCCCCC\C=C/CCCCCCCC(=O)OO XWHRTPLAQGGJDN-FPLPWBNLSA-N 0.000 description 2
- MYRTYDVEIRVNKP-UHFFFAOYSA-N 1,2-Divinylbenzene Chemical compound C=CC1=CC=CC=C1C=C MYRTYDVEIRVNKP-UHFFFAOYSA-N 0.000 description 2
- FCEHBMOGCRZNNI-UHFFFAOYSA-N 1-benzothiophene Chemical group C1=CC=C2SC=CC2=C1 FCEHBMOGCRZNNI-UHFFFAOYSA-N 0.000 description 2
- XYHKNCXZYYTLRG-UHFFFAOYSA-N 1h-imidazole-2-carbaldehyde Chemical compound O=CC1=NC=CN1 XYHKNCXZYYTLRG-UHFFFAOYSA-N 0.000 description 2
- ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 description 2
- BSKHPKMHTQYZBB-UHFFFAOYSA-N 2-methylpyridine Chemical class CC1=CC=CC=N1 BSKHPKMHTQYZBB-UHFFFAOYSA-N 0.000 description 2
- LVBXEMGDVWVTGY-SREVYHEPSA-N 2-octenal Chemical compound CCCCC\C=C/C=O LVBXEMGDVWVTGY-SREVYHEPSA-N 0.000 description 2
- GWYFCOCPABKNJV-UHFFFAOYSA-M 3-Methylbutanoic acid Natural products CC(C)CC([O-])=O GWYFCOCPABKNJV-UHFFFAOYSA-M 0.000 description 2
- YEJRWHAVMIAJKC-UHFFFAOYSA-N 4-Butyrolactone Chemical group O=C1CCCO1 YEJRWHAVMIAJKC-UHFFFAOYSA-N 0.000 description 2
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 2
- 239000004475 Arginine Substances 0.000 description 2
- FERIUCNNQQJTOY-UHFFFAOYSA-N Butyric acid Chemical compound CCCC(O)=O FERIUCNNQQJTOY-UHFFFAOYSA-N 0.000 description 2
- 239000005632 Capric acid (CAS 334-48-5) Substances 0.000 description 2
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 2
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 2
- YLQBMQCUIZJEEH-UHFFFAOYSA-N Furan Chemical group C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 2
- AHLPHDHHMVZTML-BYPYZUCNSA-N L-Ornithine Chemical compound NCCC[C@H](N)C(O)=O AHLPHDHHMVZTML-BYPYZUCNSA-N 0.000 description 2
- ODKSFYDXXFIFQN-BYPYZUCNSA-P L-argininium(2+) Chemical compound NC(=[NH2+])NCCC[C@H]([NH3+])C(O)=O ODKSFYDXXFIFQN-BYPYZUCNSA-P 0.000 description 2
- KDXKERNSBIXSRK-YFKPBYRVSA-N L-lysine Chemical compound NCCCC[C@H](N)C(O)=O KDXKERNSBIXSRK-YFKPBYRVSA-N 0.000 description 2
- 239000004472 Lysine Substances 0.000 description 2
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 2
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 2
- MBBZMMPHUWSWHV-BDVNFPICSA-N N-methylglucamine Chemical compound CNC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO MBBZMMPHUWSWHV-BDVNFPICSA-N 0.000 description 2
- AHLPHDHHMVZTML-UHFFFAOYSA-N Orn-delta-NH2 Natural products NCCCC(N)C(O)=O AHLPHDHHMVZTML-UHFFFAOYSA-N 0.000 description 2
- UTJLXEIPEHZYQJ-UHFFFAOYSA-N Ornithine Natural products OC(=O)C(C)CCCN UTJLXEIPEHZYQJ-UHFFFAOYSA-N 0.000 description 2
- OFBQJSOFQDEBGM-UHFFFAOYSA-N Pentane Chemical compound CCCCC OFBQJSOFQDEBGM-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
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 description 2
- 230000009471 action Effects 0.000 description 2
- 239000013543 active substance Substances 0.000 description 2
- 229910052784 alkaline earth metal Inorganic materials 0.000 description 2
- 125000004453 alkoxycarbonyl group Chemical group 0.000 description 2
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 2
- 150000001412 amines Chemical class 0.000 description 2
- 235000001014 amino acid Nutrition 0.000 description 2
- 150000001413 amino acids Chemical class 0.000 description 2
- RDOXTESZEPMUJZ-UHFFFAOYSA-N anisole Chemical compound COC1=CC=CC=C1 RDOXTESZEPMUJZ-UHFFFAOYSA-N 0.000 description 2
- 230000000844 anti-bacterial effect Effects 0.000 description 2
- 230000003078 antioxidant effect Effects 0.000 description 2
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 2
- 235000009697 arginine Nutrition 0.000 description 2
- 125000006615 aromatic heterocyclic group Chemical group 0.000 description 2
- 150000004945 aromatic hydrocarbons Chemical class 0.000 description 2
- 239000012298 atmosphere Substances 0.000 description 2
- TZCXTZWJZNENPQ-UHFFFAOYSA-L barium sulfate Chemical compound [Ba+2].[O-]S([O-])(=O)=O TZCXTZWJZNENPQ-UHFFFAOYSA-L 0.000 description 2
- UPABQMWFWCMOFV-UHFFFAOYSA-N benethamine Chemical compound C=1C=CC=CC=1CNCCC1=CC=CC=C1 UPABQMWFWCMOFV-UHFFFAOYSA-N 0.000 description 2
- JUHORIMYRDESRB-UHFFFAOYSA-N benzathine Chemical compound C=1C=CC=CC=1CNCCNCC1=CC=CC=C1 JUHORIMYRDESRB-UHFFFAOYSA-N 0.000 description 2
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 2
- GWYFCOCPABKNJV-UHFFFAOYSA-N beta-methyl-butyric acid Natural products CC(C)CC(O)=O GWYFCOCPABKNJV-UHFFFAOYSA-N 0.000 description 2
- QARVLSVVCXYDNA-UHFFFAOYSA-N bromobenzene Chemical compound BrC1=CC=CC=C1 QARVLSVVCXYDNA-UHFFFAOYSA-N 0.000 description 2
- DIKBFYAXUHHXCS-UHFFFAOYSA-N bromoform Chemical compound BrC(Br)Br DIKBFYAXUHHXCS-UHFFFAOYSA-N 0.000 description 2
- 150000004649 carbonic acid derivatives Chemical class 0.000 description 2
- 230000003197 catalytic effect Effects 0.000 description 2
- MVPPADPHJFYWMZ-UHFFFAOYSA-N chlorobenzene Chemical compound ClC1=CC=CC=C1 MVPPADPHJFYWMZ-UHFFFAOYSA-N 0.000 description 2
- 239000006071 cream Substances 0.000 description 2
- 238000002425 crystallisation Methods 0.000 description 2
- 230000008025 crystallization Effects 0.000 description 2
- PAFZNILMFXTMIY-UHFFFAOYSA-N cyclohexylamine Chemical class NC1CCCCC1 PAFZNILMFXTMIY-UHFFFAOYSA-N 0.000 description 2
- 230000001877 deodorizing effect Effects 0.000 description 2
- 229940000033 dermatological agent Drugs 0.000 description 2
- 239000003241 dermatological agent Substances 0.000 description 2
- HPNMFZURTQLUMO-UHFFFAOYSA-N diethylamine Chemical class CCNCC HPNMFZURTQLUMO-UHFFFAOYSA-N 0.000 description 2
- 239000000839 emulsion Substances 0.000 description 2
- 210000005175 epidermal keratinocyte Anatomy 0.000 description 2
- 238000011156 evaluation Methods 0.000 description 2
- 230000001747 exhibiting effect Effects 0.000 description 2
- 239000000835 fiber Substances 0.000 description 2
- 239000000499 gel Substances 0.000 description 2
- ZNNLBTZKUZBEKO-UHFFFAOYSA-N glyburide Chemical compound COC1=CC=C(Cl)C=C1C(=O)NCCC1=CC=C(S(=O)(=O)NC(=O)NC2CCCCC2)C=C1 ZNNLBTZKUZBEKO-UHFFFAOYSA-N 0.000 description 2
- 150000008282 halocarbons Chemical class 0.000 description 2
- 238000001319 headspace solid-phase micro-extraction Methods 0.000 description 2
- 230000036074 healthy skin Effects 0.000 description 2
- 150000004679 hydroxides Chemical class 0.000 description 2
- 239000006210 lotion Substances 0.000 description 2
- 235000018977 lysine Nutrition 0.000 description 2
- VTHJTEIRLNZDEV-UHFFFAOYSA-L magnesium dihydroxide Chemical compound [OH-].[OH-].[Mg+2] VTHJTEIRLNZDEV-UHFFFAOYSA-L 0.000 description 2
- 239000000347 magnesium hydroxide Substances 0.000 description 2
- 229910001862 magnesium hydroxide Inorganic materials 0.000 description 2
- 239000002609 medium Substances 0.000 description 2
- 229910052751 metal Inorganic materials 0.000 description 2
- 239000002184 metal Substances 0.000 description 2
- 150000007522 mineralic acids Chemical class 0.000 description 2
- PSHKMPUSSFXUIA-UHFFFAOYSA-N n,n-dimethylpyridin-2-amine Chemical class CN(C)C1=CC=CC=N1 PSHKMPUSSFXUIA-UHFFFAOYSA-N 0.000 description 2
- 125000001624 naphthyl group Chemical group 0.000 description 2
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 2
- 229910052757 nitrogen Inorganic materials 0.000 description 2
- 125000004433 nitrogen atom Chemical group N* 0.000 description 2
- 150000007524 organic acids Chemical class 0.000 description 2
- 150000007530 organic bases Chemical class 0.000 description 2
- 229960003104 ornithine Drugs 0.000 description 2
- 125000001820 oxy group Chemical group [*:1]O[*:2] 0.000 description 2
- 125000004430 oxygen atom Chemical group O* 0.000 description 2
- 229910052763 palladium Inorganic materials 0.000 description 2
- YBYRMVIVWMBXKQ-UHFFFAOYSA-N phenylmethanesulfonyl fluoride Chemical compound FS(=O)(=O)CC1=CC=CC=C1 YBYRMVIVWMBXKQ-UHFFFAOYSA-N 0.000 description 2
- OJMIONKXNSYLSR-UHFFFAOYSA-N phosphorous acid Chemical compound OP(O)O OJMIONKXNSYLSR-UHFFFAOYSA-N 0.000 description 2
- 125000004437 phosphorous atom Chemical group 0.000 description 2
- 229910052698 phosphorus Inorganic materials 0.000 description 2
- XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 2
- BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 description 2
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 2
- MFDFERRIHVXMIY-UHFFFAOYSA-N procaine Chemical class CCN(CC)CCOC(=O)C1=CC=C(N)C=C1 MFDFERRIHVXMIY-UHFFFAOYSA-N 0.000 description 2
- 229960004919 procaine Drugs 0.000 description 2
- 230000009467 reduction Effects 0.000 description 2
- 210000002374 sebum Anatomy 0.000 description 2
- 238000000926 separation method Methods 0.000 description 2
- 210000004927 skin cell Anatomy 0.000 description 2
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 2
- 235000017557 sodium bicarbonate Nutrition 0.000 description 2
- 238000002470 solid-phase micro-extraction Methods 0.000 description 2
- 241000894007 species Species 0.000 description 2
- 230000001629 suppression Effects 0.000 description 2
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 2
- LVBXEMGDVWVTGY-UHFFFAOYSA-N trans-2-octenal Natural products CCCCCC=CC=O LVBXEMGDVWVTGY-UHFFFAOYSA-N 0.000 description 2
- IIYFAKIEWZDVMP-UHFFFAOYSA-N tridecane Chemical compound CCCCCCCCCCCCC IIYFAKIEWZDVMP-UHFFFAOYSA-N 0.000 description 2
- VYXLXSNBECGAOH-UHFFFAOYSA-N $l^{1}-azanylcyclohexane Chemical compound [N]C1CCCCC1 VYXLXSNBECGAOH-UHFFFAOYSA-N 0.000 description 1
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 description 1
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 description 1
- 125000006651 (C3-C20) cycloalkyl group Chemical group 0.000 description 1
- UGUHFDPGDQDVGX-UHFFFAOYSA-N 1,2,3-thiadiazole Chemical group C1=CSN=N1 UGUHFDPGDQDVGX-UHFFFAOYSA-N 0.000 description 1
- QWUWMCYKGHVNAV-UHFFFAOYSA-N 1,2-dihydrostilbene Chemical class C=1C=CC=CC=1CCC1=CC=CC=C1 QWUWMCYKGHVNAV-UHFFFAOYSA-N 0.000 description 1
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
- FLBAYUMRQUHISI-UHFFFAOYSA-N 1,8-naphthyridine Chemical group N1=CC=CC2=CC=CN=C21 FLBAYUMRQUHISI-UHFFFAOYSA-N 0.000 description 1
- IANQTJSKSUMEQM-UHFFFAOYSA-N 1-benzofuran Chemical group C1=CC=C2OC=CC2=C1 IANQTJSKSUMEQM-UHFFFAOYSA-N 0.000 description 1
- 125000004973 1-butenyl group Chemical group C(=CCC)* 0.000 description 1
- MCTWTZJPVLRJOU-UHFFFAOYSA-N 1-methyl-1H-imidazole Chemical compound CN1C=CN=C1 MCTWTZJPVLRJOU-UHFFFAOYSA-N 0.000 description 1
- 125000004214 1-pyrrolidinyl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 description 1
- VLJLXEKIAALSJE-UHFFFAOYSA-N 13-oxabicyclo[10.1.0]tridecane Chemical compound C1CCCCCCCCCC2OC21 VLJLXEKIAALSJE-UHFFFAOYSA-N 0.000 description 1
- NTFPDEDRMYYPAC-UHFFFAOYSA-N 2-amino-4-[[3-(carboxymethyl)phenoxy]-methoxyphosphoryl]butanoic acid Chemical compound OC(=O)C(N)CCP(=O)(OC)OC1=CC=CC(CC(O)=O)=C1 NTFPDEDRMYYPAC-UHFFFAOYSA-N 0.000 description 1
- UXGVMFHEKMGWMA-UHFFFAOYSA-N 2-benzofuran Chemical group C1=CC=CC2=COC=C21 UXGVMFHEKMGWMA-UHFFFAOYSA-N 0.000 description 1
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 description 1
- ZSCDRSWJZRRPGN-UHFFFAOYSA-N 4-oxahomoadamantan-5-one Chemical group C1C(C2)C(=O)OC3CC1CC2C3 ZSCDRSWJZRRPGN-UHFFFAOYSA-N 0.000 description 1
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical group [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
- KDCGOANMDULRCW-UHFFFAOYSA-N 7H-purine Chemical group N1=CNC2=NC=NC2=C1 KDCGOANMDULRCW-UHFFFAOYSA-N 0.000 description 1
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 1
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical group [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
- 229920000742 Cotton Polymers 0.000 description 1
- BWLUMTFWVZZZND-UHFFFAOYSA-N Dibenzylamine Chemical compound C=1C=CC=CC=1CNCC1=CC=CC=C1 BWLUMTFWVZZZND-UHFFFAOYSA-N 0.000 description 1
- OIFBSDVPJOWBCH-UHFFFAOYSA-N Diethyl carbonate Chemical compound CCOC(=O)OCC OIFBSDVPJOWBCH-UHFFFAOYSA-N 0.000 description 1
- KMTRUDSVKNLOMY-UHFFFAOYSA-N Ethylene carbonate Chemical compound O=C1OCCO1 KMTRUDSVKNLOMY-UHFFFAOYSA-N 0.000 description 1
- 101710107035 Gamma-glutamyltranspeptidase Proteins 0.000 description 1
- 108010063907 Glutathione Reductase Proteins 0.000 description 1
- 101710173228 Glutathione hydrolase proenzyme Proteins 0.000 description 1
- 102100036442 Glutathione reductase, mitochondrial Human genes 0.000 description 1
- ODKSFYDXXFIFQN-BYPYZUCNSA-N L-arginine Chemical compound OC(=O)[C@@H](N)CCCN=C(N)N ODKSFYDXXFIFQN-BYPYZUCNSA-N 0.000 description 1
- 229930064664 L-arginine Natural products 0.000 description 1
- 235000014852 L-arginine Nutrition 0.000 description 1
- 238000005654 Michaelis-Arbuzov synthesis reaction Methods 0.000 description 1
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical group C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 1
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 1
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 1
- 241000219925 Oenothera Species 0.000 description 1
- 235000004496 Oenothera biennis Nutrition 0.000 description 1
- 229940121708 Oxygenase inhibitor Drugs 0.000 description 1
- 102000004020 Oxygenases Human genes 0.000 description 1
- 108090000417 Oxygenases Proteins 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- 235000004347 Perilla Nutrition 0.000 description 1
- 244000124853 Perilla frutescens Species 0.000 description 1
- GOOHAUXETOMSMM-UHFFFAOYSA-N Propylene oxide Chemical compound CC1CO1 GOOHAUXETOMSMM-UHFFFAOYSA-N 0.000 description 1
- CVQUWLDCFXOXEN-UHFFFAOYSA-N Pyran-4-one Chemical group O=C1C=COC=C1 CVQUWLDCFXOXEN-UHFFFAOYSA-N 0.000 description 1
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical group C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 1
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 1
- DHXVGJBLRPWPCS-UHFFFAOYSA-N Tetrahydropyran Chemical group C1CCOCC1 DHXVGJBLRPWPCS-UHFFFAOYSA-N 0.000 description 1
- FZWLAAWBMGSTSO-UHFFFAOYSA-N Thiazole Chemical group C1=CSC=N1 FZWLAAWBMGSTSO-UHFFFAOYSA-N 0.000 description 1
- YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical group C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 description 1
- VYGUBTIWNBFFMQ-UHFFFAOYSA-N [N+](#[C-])N1C(=O)NC=2NC(=O)NC2C1=O Chemical group [N+](#[C-])N1C(=O)NC=2NC(=O)NC2C1=O VYGUBTIWNBFFMQ-UHFFFAOYSA-N 0.000 description 1
- 239000003377 acid catalyst Substances 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 125000000641 acridinyl group Chemical group C1(=CC=CC2=NC3=CC=CC=C3C=C12)* 0.000 description 1
- 125000002252 acyl group Chemical group 0.000 description 1
- 125000004442 acylamino group Chemical group 0.000 description 1
- 125000004423 acyloxy group Chemical group 0.000 description 1
- 125000005073 adamantyl group Chemical group C12(CC3CC(CC(C1)C3)C2)* 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 230000000996 additive effect Effects 0.000 description 1
- 150000001298 alcohols Chemical class 0.000 description 1
- 229910000288 alkali metal carbonate Inorganic materials 0.000 description 1
- 150000008041 alkali metal carbonates Chemical class 0.000 description 1
- 229910000318 alkali metal phosphate Inorganic materials 0.000 description 1
- 150000001340 alkali metals Chemical class 0.000 description 1
- 150000001342 alkaline earth metals Chemical class 0.000 description 1
- 125000004450 alkenylene group Chemical group 0.000 description 1
- 125000003302 alkenyloxy group Chemical group 0.000 description 1
- 150000004703 alkoxides Chemical class 0.000 description 1
- 125000003282 alkyl amino group Chemical group 0.000 description 1
- 125000002947 alkylene group Chemical group 0.000 description 1
- 125000000304 alkynyl group Chemical group 0.000 description 1
- OENHQHLEOONYIE-UKMVMLAPSA-N all-trans beta-carotene Natural products CC=1CCCC(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 OENHQHLEOONYIE-UKMVMLAPSA-N 0.000 description 1
- 150000001408 amides Chemical class 0.000 description 1
- 229910021529 ammonia Inorganic materials 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 239000003242 anti bacterial agent Substances 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 239000012300 argon atmosphere Substances 0.000 description 1
- 125000002102 aryl alkyloxo group Chemical group 0.000 description 1
- 125000005161 aryl oxy carbonyl group Chemical group 0.000 description 1
- 229910052788 barium Inorganic materials 0.000 description 1
- DSAJWYNOEDNPEQ-UHFFFAOYSA-N barium atom Chemical compound [Ba] DSAJWYNOEDNPEQ-UHFFFAOYSA-N 0.000 description 1
- 159000000009 barium salts Chemical class 0.000 description 1
- 125000000649 benzylidene group Chemical group [H]C(=[*])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 1
- 125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 description 1
- 235000013734 beta-carotene Nutrition 0.000 description 1
- 239000011648 beta-carotene Substances 0.000 description 1
- TUPZEYHYWIEDIH-WAIFQNFQSA-N beta-carotene Natural products CC(=C/C=C/C=C(C)/C=C/C=C(C)/C=C/C1=C(C)CCCC1(C)C)C=CC=C(/C)C=CC2=CCCCC2(C)C TUPZEYHYWIEDIH-WAIFQNFQSA-N 0.000 description 1
- 229960002747 betacarotene Drugs 0.000 description 1
- KGBXLFKZBHKPEV-UHFFFAOYSA-N boric acid Chemical compound OB(O)O KGBXLFKZBHKPEV-UHFFFAOYSA-N 0.000 description 1
- 239000004327 boric acid Substances 0.000 description 1
- WVQUCYVTZWVNLV-UHFFFAOYSA-N boric acid;oxalic acid Chemical compound OB(O)O.OC(=O)C(O)=O WVQUCYVTZWVNLV-UHFFFAOYSA-N 0.000 description 1
- 229950005228 bromoform Drugs 0.000 description 1
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- AXCZMVOFGPJBDE-UHFFFAOYSA-L calcium dihydroxide Chemical compound [OH-].[OH-].[Ca+2] AXCZMVOFGPJBDE-UHFFFAOYSA-L 0.000 description 1
- 239000000920 calcium hydroxide Substances 0.000 description 1
- 229910001861 calcium hydroxide Inorganic materials 0.000 description 1
- BRPQOXSCLDDYGP-UHFFFAOYSA-N calcium oxide Chemical compound [O-2].[Ca+2] BRPQOXSCLDDYGP-UHFFFAOYSA-N 0.000 description 1
- 239000000292 calcium oxide Substances 0.000 description 1
- ODINCKMPIJJUCX-UHFFFAOYSA-N calcium oxide Inorganic materials [Ca]=O ODINCKMPIJJUCX-UHFFFAOYSA-N 0.000 description 1
- 159000000007 calcium salts Chemical class 0.000 description 1
- 150000007942 carboxylates Chemical class 0.000 description 1
- 239000003729 cation exchange resin Substances 0.000 description 1
- 229920001429 chelating resin Polymers 0.000 description 1
- 229910052801 chlorine Inorganic materials 0.000 description 1
- 125000001309 chloro group Chemical group Cl* 0.000 description 1
- VZWXIQHBIQLMPN-UHFFFAOYSA-N chromane Chemical group C1=CC=C2CCCOC2=C1 VZWXIQHBIQLMPN-UHFFFAOYSA-N 0.000 description 1
- OTAFHZMPRISVEM-UHFFFAOYSA-N chromone Chemical group C1=CC=C2C(=O)C=COC2=C1 OTAFHZMPRISVEM-UHFFFAOYSA-N 0.000 description 1
- 239000011248 coating agent Substances 0.000 description 1
- 238000004440 column chromatography Methods 0.000 description 1
- 150000005676 cyclic carbonates Chemical class 0.000 description 1
- 125000004122 cyclic group Chemical group 0.000 description 1
- 125000000392 cycloalkenyl group Chemical group 0.000 description 1
- 125000000753 cycloalkyl group Chemical group 0.000 description 1
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
- 125000000596 cyclohexenyl group Chemical group C1(=CCCCC1)* 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
- 125000004210 cyclohexylmethyl group Chemical group [H]C([H])(*)C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 description 1
- 125000000640 cyclooctyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 description 1
- 125000002433 cyclopentenyl group Chemical group C1(=CCCC1)* 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
- 125000004851 cyclopentylmethyl group Chemical group C1(CCCC1)C* 0.000 description 1
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 1
- XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 description 1
- 235000018417 cysteine Nutrition 0.000 description 1
- 238000000354 decomposition reaction Methods 0.000 description 1
- 125000002704 decyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- IEJIGPNLZYLLBP-UHFFFAOYSA-N dimethyl carbonate Chemical compound COC(=O)OC IEJIGPNLZYLLBP-UHFFFAOYSA-N 0.000 description 1
- 239000004205 dimethyl polysiloxane Substances 0.000 description 1
- 238000004821 distillation Methods 0.000 description 1
- 125000003438 dodecyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- 239000004210 ether based solvent Substances 0.000 description 1
- 150000002170 ethers Chemical class 0.000 description 1
- JBTWLSYIZRCDFO-UHFFFAOYSA-N ethyl methyl carbonate Chemical compound CCOC(=O)OC JBTWLSYIZRCDFO-UHFFFAOYSA-N 0.000 description 1
- LVGKNOAMLMIIKO-QXMHVHEDSA-N ethyl oleate Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OCC LVGKNOAMLMIIKO-QXMHVHEDSA-N 0.000 description 1
- 125000002534 ethynyl group Chemical group [H]C#C* 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 229910052731 fluorine Inorganic materials 0.000 description 1
- 125000001153 fluoro group Chemical group F* 0.000 description 1
- 238000001640 fractional crystallisation Methods 0.000 description 1
- 102000006640 gamma-Glutamyltransferase Human genes 0.000 description 1
- 238000004817 gas chromatography Methods 0.000 description 1
- 239000001963 growth medium Substances 0.000 description 1
- 150000004820 halides Chemical class 0.000 description 1
- 229910052736 halogen Inorganic materials 0.000 description 1
- 230000002140 halogenating effect Effects 0.000 description 1
- 150000002367 halogens Chemical class 0.000 description 1
- ARGGOKUVIPUXPJ-UHFFFAOYSA-N hexahydro-2h-3,5-methanocyclopenta[b]furan-2-one Chemical group C1C2C3OC(=O)C2CC1C3 ARGGOKUVIPUXPJ-UHFFFAOYSA-N 0.000 description 1
- 125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 229930195733 hydrocarbon Natural products 0.000 description 1
- 125000002883 imidazolyl group Chemical group 0.000 description 1
- 125000003387 indolinyl group Chemical group N1(CCC2=CC=CC=C12)* 0.000 description 1
- 125000001041 indolyl group Chemical group 0.000 description 1
- 229910052740 iodine Inorganic materials 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
- HEBMCVBCEDMUOF-UHFFFAOYSA-N isochromane Chemical group C1=CC=C2COCCC2=C1 HEBMCVBCEDMUOF-UHFFFAOYSA-N 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- ZLTPDFXIESTBQG-UHFFFAOYSA-N isothiazole Chemical group C=1C=NSC=1 ZLTPDFXIESTBQG-UHFFFAOYSA-N 0.000 description 1
- 125000000842 isoxazolyl group Chemical group 0.000 description 1
- 150000002576 ketones Chemical class 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 159000000003 magnesium salts Chemical class 0.000 description 1
- 230000010534 mechanism of action Effects 0.000 description 1
- 230000004060 metabolic process Effects 0.000 description 1
- UZKWTJUDCOPSNM-UHFFFAOYSA-N methoxybenzene Substances CCCCOC=C UZKWTJUDCOPSNM-UHFFFAOYSA-N 0.000 description 1
- 229910000402 monopotassium phosphate Inorganic materials 0.000 description 1
- 235000019796 monopotassium phosphate Nutrition 0.000 description 1
- 229910000403 monosodium phosphate Inorganic materials 0.000 description 1
- 235000019799 monosodium phosphate Nutrition 0.000 description 1
- ULWOJODHECIZAU-UHFFFAOYSA-N n,n-diethylpropan-2-amine Chemical compound CCN(CC)C(C)C ULWOJODHECIZAU-UHFFFAOYSA-N 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
- 229910017604 nitric acid Inorganic materials 0.000 description 1
- 150000002825 nitriles Chemical class 0.000 description 1
- 239000012299 nitrogen atmosphere Substances 0.000 description 1
- LYGJENNIWJXYER-UHFFFAOYSA-N nitromethane Chemical compound C[N+]([O-])=O LYGJENNIWJXYER-UHFFFAOYSA-N 0.000 description 1
- 231100001083 no cytotoxicity Toxicity 0.000 description 1
- 125000002868 norbornyl group Chemical group C12(CCC(CC1)C2)* 0.000 description 1
- 238000010899 nucleation Methods 0.000 description 1
- 239000002674 ointment Substances 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 125000000962 organic group Chemical group 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 235000006408 oxalic acid Nutrition 0.000 description 1
- 125000002971 oxazolyl group Chemical group 0.000 description 1
- 125000003566 oxetanyl group Chemical group 0.000 description 1
- 125000000466 oxiranyl group Chemical group 0.000 description 1
- 125000004043 oxo group Chemical group O=* 0.000 description 1
- 125000005740 oxycarbonyl group Chemical group [*:1]OC([*:2])=O 0.000 description 1
- 239000003650 oxygenase inhibitor Substances 0.000 description 1
- 125000006503 p-nitrobenzyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1[N+]([O-])=O)C([H])([H])* 0.000 description 1
- 125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
- 239000003208 petroleum Substances 0.000 description 1
- 235000021317 phosphate Nutrition 0.000 description 1
- 239000008363 phosphate buffer Substances 0.000 description 1
- 125000002467 phosphate group Chemical group [H]OP(=O)(O[H])O[*] 0.000 description 1
- ABLZXFCXXLZCGV-UHFFFAOYSA-N phosphonic acid group Chemical group P(O)(O)=O ABLZXFCXXLZCGV-UHFFFAOYSA-N 0.000 description 1
- 150000003013 phosphoric acid derivatives Chemical class 0.000 description 1
- PJNZPQUBCPKICU-UHFFFAOYSA-N phosphoric acid;potassium Chemical compound [K].OP(O)(O)=O PJNZPQUBCPKICU-UHFFFAOYSA-N 0.000 description 1
- DHRLEVQXOMLTIM-UHFFFAOYSA-N phosphoric acid;trioxomolybdenum Chemical compound O=[Mo](=O)=O.O=[Mo](=O)=O.O=[Mo](=O)=O.O=[Mo](=O)=O.O=[Mo](=O)=O.O=[Mo](=O)=O.O=[Mo](=O)=O.O=[Mo](=O)=O.O=[Mo](=O)=O.O=[Mo](=O)=O.O=[Mo](=O)=O.O=[Mo](=O)=O.OP(O)(O)=O DHRLEVQXOMLTIM-UHFFFAOYSA-N 0.000 description 1
- UHZYTMXLRWXGPK-UHFFFAOYSA-N phosphorus pentachloride Chemical compound ClP(Cl)(Cl)(Cl)Cl UHZYTMXLRWXGPK-UHFFFAOYSA-N 0.000 description 1
- 125000004193 piperazinyl group Chemical group 0.000 description 1
- 125000003386 piperidinyl group Chemical group 0.000 description 1
- 229910052697 platinum Inorganic materials 0.000 description 1
- 239000002798 polar solvent Substances 0.000 description 1
- 229920000435 poly(dimethylsiloxane) Polymers 0.000 description 1
- 150000008442 polyphenolic compounds Chemical class 0.000 description 1
- 235000013824 polyphenols Nutrition 0.000 description 1
- XAEFZNCEHLXOMS-UHFFFAOYSA-M potassium benzoate Chemical compound [K+].[O-]C(=O)C1=CC=CC=C1 XAEFZNCEHLXOMS-UHFFFAOYSA-M 0.000 description 1
- 239000011736 potassium bicarbonate Substances 0.000 description 1
- 229910000028 potassium bicarbonate Inorganic materials 0.000 description 1
- 235000015497 potassium bicarbonate Nutrition 0.000 description 1
- 229910000027 potassium carbonate Inorganic materials 0.000 description 1
- 235000011181 potassium carbonates Nutrition 0.000 description 1
- TYJJADVDDVDEDZ-UHFFFAOYSA-M potassium hydrogencarbonate Chemical compound [K+].OC([O-])=O TYJJADVDDVDEDZ-UHFFFAOYSA-M 0.000 description 1
- 229940086066 potassium hydrogencarbonate Drugs 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- 230000035755 proliferation Effects 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- RUOJZAUFBMNUDX-UHFFFAOYSA-N propylene carbonate Chemical compound CC1COC(=O)O1 RUOJZAUFBMNUDX-UHFFFAOYSA-N 0.000 description 1
- 125000002568 propynyl group Chemical group [*]C#CC([H])([H])[H] 0.000 description 1
- 125000004309 pyranyl group Chemical group O1C(C=CC=C1)* 0.000 description 1
- 125000003373 pyrazinyl group Chemical group 0.000 description 1
- 125000003226 pyrazolyl group Chemical group 0.000 description 1
- PBMFSQRYOILNGV-UHFFFAOYSA-N pyridazine Chemical group C1=CC=NN=C1 PBMFSQRYOILNGV-UHFFFAOYSA-N 0.000 description 1
- 125000000714 pyrimidinyl group Chemical group 0.000 description 1
- 125000000168 pyrrolyl group Chemical group 0.000 description 1
- 125000002294 quinazolinyl group Chemical group N1=C(N=CC2=CC=CC=C12)* 0.000 description 1
- 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 239000000376 reactant Substances 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 230000009257 reactivity Effects 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 238000004064 recycling Methods 0.000 description 1
- 230000003716 rejuvenation Effects 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- 229930195734 saturated hydrocarbon Natural products 0.000 description 1
- 210000001732 sebaceous gland Anatomy 0.000 description 1
- 244000005714 skin microbiome Species 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- 235000017550 sodium carbonate Nutrition 0.000 description 1
- AJPJDKMHJJGVTQ-UHFFFAOYSA-M sodium dihydrogen phosphate Chemical compound [Na+].OP(O)([O-])=O AJPJDKMHJJGVTQ-UHFFFAOYSA-M 0.000 description 1
- QDRKDTQENPPHOJ-UHFFFAOYSA-N sodium ethoxide Chemical compound [Na+].CC[O-] QDRKDTQENPPHOJ-UHFFFAOYSA-N 0.000 description 1
- 239000012312 sodium hydride Substances 0.000 description 1
- 229910000104 sodium hydride Inorganic materials 0.000 description 1
- 159000000000 sodium salts Chemical class 0.000 description 1
- 239000000243 solution Substances 0.000 description 1
- 238000000527 sonication Methods 0.000 description 1
- 238000001179 sorption measurement Methods 0.000 description 1
- 239000007921 spray Substances 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 125000000547 substituted alkyl group Chemical group 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- WPLOVIFNBMNBPD-ATHMIXSHSA-N subtilin Chemical compound CC1SCC(NC2=O)C(=O)NC(CC(N)=O)C(=O)NC(C(=O)NC(CCCCN)C(=O)NC(C(C)CC)C(=O)NC(=C)C(=O)NC(CCCCN)C(O)=O)CSC(C)C2NC(=O)C(CC(C)C)NC(=O)C1NC(=O)C(CCC(N)=O)NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C1NC(=O)C(=C/C)/NC(=O)C(CCC(N)=O)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)CNC(=O)C(NC(=O)C(NC(=O)C2NC(=O)CNC(=O)C3CCCN3C(=O)C(NC(=O)C3NC(=O)C(CC(C)C)NC(=O)C(=C)NC(=O)C(CCC(O)=O)NC(=O)C(NC(=O)C(CCCCN)NC(=O)C(N)CC=4C5=CC=CC=C5NC=4)CSC3)C(C)SC2)C(C)C)C(C)SC1)CC1=CC=CC=C1 WPLOVIFNBMNBPD-ATHMIXSHSA-N 0.000 description 1
- 125000000020 sulfo group Chemical group O=S(=O)([*])O[H] 0.000 description 1
- HXJUTPCZVOIRIF-UHFFFAOYSA-N sulfolane Chemical compound O=S1(=O)CCCC1 HXJUTPCZVOIRIF-UHFFFAOYSA-N 0.000 description 1
- 150000003457 sulfones Chemical class 0.000 description 1
- 125000006296 sulfonyl amino group Chemical group [H]N(*)S(*)(=O)=O 0.000 description 1
- 150000003462 sulfoxides Chemical class 0.000 description 1
- 229910052717 sulfur Inorganic materials 0.000 description 1
- 125000004434 sulfur atom Chemical group 0.000 description 1
- 210000000106 sweat gland Anatomy 0.000 description 1
- 208000024891 symptom Diseases 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
- GYDJEQRTZSCIOI-LJGSYFOKSA-N tranexamic acid Chemical compound NC[C@H]1CC[C@H](C(O)=O)CC1 GYDJEQRTZSCIOI-LJGSYFOKSA-N 0.000 description 1
- 229960000401 tranexamic acid Drugs 0.000 description 1
- 229910052723 transition metal Inorganic materials 0.000 description 1
- 125000001425 triazolyl group Chemical group 0.000 description 1
- 229930195735 unsaturated hydrocarbon Natural products 0.000 description 1
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
- 229920002554 vinyl polymer Polymers 0.000 description 1
- 239000008096 xylene Substances 0.000 description 1
- OENHQHLEOONYIE-JLTXGRSLSA-N β-Carotene Chemical compound CC=1CCCC(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 OENHQHLEOONYIE-JLTXGRSLSA-N 0.000 description 1
Images
Landscapes
- Cosmetics (AREA)
Abstract
Description
本発明は、体臭抑制剤に関する。 The present invention relates to a body odor suppressant.
近年、衛生志向が高まり、体臭が嫌悪される傾向が強まっている。体臭には、腋臭、足臭、加齢臭等が含まれる。腋臭や足臭の主な原因物質としては、イソ吉草酸、ノナン酸、カプリン酸等の低級脂肪酸が知られている。また、加齢臭の主な原因物質としては、２−オクテナールや２−ノネナール等の不飽和アルデヒドが知られている。 In recent years, hygiene consciousness has increased, and the tendency for body odor to be disliked has increased. Body odor includes axillary odor, foot odor, aging odor and the like. Lower fatty acids such as isovaleric acid, nonanoic acid, and capric acid are known as main causes of axillary odor and foot odor. As a main cause substance of the aging odor, unsaturated aldehydes such as 2-octenal and 2-nonenal are known.
特許文献１には、１３−オキサビシクロ［１０．１．０］トリデカン類を含有する抗菌剤を使用して、腋臭の発生に関与する皮膚常在菌の増殖を抑制することにより、体臭を抑制する方法が記載されている。しかし、この方法によれば、皮膚常在菌のうち健康な皮膚を維持する為に欠かせない菌も増殖が抑制されるので、体臭は抑制されても、他の問題が新たに発生する恐れがあった。 Patent Document 1 discloses that an antibacterial agent containing 13-oxabicyclo [10.1.0] tridecane is used to suppress the growth of bacteria indigenous to the skin involved in the generation of axillary odor, thereby suppressing body odor. A method is described. However, according to this method, among the indigenous bacteria of the skin, bacteria that are indispensable for maintaining healthy skin are also suppressed from growing, so even if body odor is suppressed, other problems may newly occur. was there.
また、特許文献２には、加齢により皮脂中において含有比率が高まるパルミトレイン酸が表在菌の酸素添加酵素によってパルミトレイン酸ヒドロペルオキシドへと酸化され、次いでこのパルミトレイン酸ヒドロペルオキシドがβ開裂することでオクテナールや２−ノネナール等の不飽和アルデヒドが生成することが記載され、トラネキサム酸やβ−カロチン等の脂肪酸酸素添加酵素阻害剤を使用することで前記不飽和アルデヒドの生成を抑制することができることが記載されている。 In addition, Patent Document 2 discloses that palmitoleic acid, whose content in sebum increases with aging, is oxidized to palmitoleic acid hydroperoxide by an oxygenase of a superficial bacterium, and then the palmitoleic acid hydroperoxide is cleaved by β. It is described that unsaturated aldehydes such as octenal and 2-nonenal are generated, and the generation of the unsaturated aldehyde can be suppressed by using a fatty acid oxygenase inhibitor such as tranexamic acid or β-carotene. Has been described.
その他、特許文献３には、シソ及び月見草由来のポリフェノールを体内に摂取すると、オクテナールや２−ノネナール等の不飽和アルデヒドの生成が抑制されることが記載されている。 In addition, Patent Document 3 describes that when polyphenols derived from perilla and evening primrose are taken into the body, the production of unsaturated aldehydes such as octenal and 2-nonenal is suppressed.
特許文献２、３の方法によれば加齢臭の原因となる不飽和アルデヒドの生成を抑制することはできるが、一旦生成された不飽和アルデヒドについてはその臭気を抑制することはできなかった。 According to the methods of Patent Documents 2 and 3, the generation of unsaturated aldehyde causing an aging odor can be suppressed, but the odor of unsaturated aldehyde once generated cannot be suppressed.
従って、本発明の目的は、体臭の原因物質の揮発性を低下させることにより、臭いの発生を抑制する効果を発揮する、体臭抑制剤を提供することにある。
本発明の他の目的は、体臭の原因物質の産生を抑制し、且つ産生された体臭の原因物質の揮発性を低下させることにより、臭いの発生を抑制する効果を発揮する、体臭抑制剤を提供することにある。
Accordingly, an object of the present invention is to provide a body odor suppressant that exhibits an effect of suppressing the generation of odor by reducing the volatility of a substance causing the body odor.
Another object of the present invention is to provide a body odor suppressant which suppresses the production of a substance causing body odor and reduces the volatility of the substance causing body odor, thereby exhibiting an effect of suppressing generation of odor. To provide.
本発明者等は上記課題を解決するため鋭意検討した結果、下記事項を見いだした。
１．グルタチオンは体臭の原因物質に速やかに付加反応することにより、体臭の原因物質を高分子量化し、高極性化して、揮発性を著しく低下させること
２．グルタチオンは、体内において抗酸化作用、細胞賦活作用等を発揮して、体臭の原因物質の産生を抑制する効果を発揮すること
３．下記式（１）で表される化合物、その塩、及びそれらの水和物は、グルタチオンの合成促進効果に優れ、皮膚に適用することによりグルタチオン濃度を速やかに上昇させることができること
４．皮膚表面の、体臭の原因物質が存する部位に、下記式（１）で表される化合物、その塩、及びそれらの水和物を適用すると、これを適用することにより生成したグルタチオンが体臭の原因物質の産生を抑制し、且つ産生された体臭の原因物質には、揮発性を低下させるよう作用することにより体臭を抑制する効果を発揮すること
本発明はこれらの知見に基づいて完成させたものである。
The present inventors have conducted intensive studies to solve the above-mentioned problems, and as a result, have found the following matters.
1. 1. Glutathione rapidly adds to the substance causing body odor, thereby increasing the molecular weight of the substance causing body odor, increasing its polarity, and significantly reducing volatility. 2. Glutathione exerts an antioxidant action, a cell activating action, and the like in the body, and exerts an effect of suppressing the production of substances causing body odor. 3. The compound represented by the following formula (1), a salt thereof, and a hydrate thereof are excellent in promoting the synthesis of glutathione, and can rapidly increase the glutathione concentration when applied to the skin. When a compound represented by the following formula (1), a salt thereof, and a hydrate thereof are applied to a site on the skin surface where a substance causing body odor exists, glutathione generated by applying the compound, the salt thereof, and the hydrate thereof cause the body odor. The present invention has been completed based on these findings by suppressing the production of substances and exerting an effect of suppressing body odor by acting to reduce volatility to the causative substance of the generated body odor. It is.
すなわち、本発明は、下記式（１）
で表される化合物、その塩、及びそれらの水和物から選択される少なくとも１種を有効成分として含む、体臭抑制剤を提供する。
That is, the present invention provides the following formula (1)
The present invention provides a body odor suppressant comprising, as an active ingredient, at least one selected from a compound represented by the formula:
本発明の体臭抑制剤は、皮膚に適用すると、皮膚細胞内においてグルタチオン濃度を速やかに上昇させることができる。そして、産生されたグルタチオンは体臭の原因物質と速やかに反応して高分子量化し、高極性化することにより、不揮発化して、臭いの発生を抑制することができる。また、産生したグルタチオンは、体臭の原因物質の産生を抑制する効果も発揮することができる。
更に、上記式（１）で表される化合物、その塩、及びそれらの水和物は、それ自体は抗菌性を有さず、安全性に優れる。そのため、これを使用しても、健康な皮膚を維持する為に欠かせない皮膚常在菌が損なわれることはない。
When applied to the skin, the body odor suppressant of the present invention can rapidly increase the glutathione concentration in skin cells. Then, the produced glutathione quickly reacts with a substance causing body odor to have a high molecular weight and become highly polar, so that it becomes non-volatile and can suppress generation of odor. Further, the produced glutathione can also exert an effect of suppressing the production of a substance causing body odor.
Furthermore, the compound represented by the formula (1), a salt thereof, and a hydrate thereof have no antibacterial properties themselves and are excellent in safety. Therefore, its use does not impair the indigenous skin bacteria essential for maintaining healthy skin.
［体臭抑制剤］
本発明の体臭抑制剤は、有効成分として、下記式（１）で表される化合物、その塩、及びそれらの水和物から選択される少なくとも１種を含む。
[Body odor suppressant]
The body odor suppressant of the present invention contains, as an active ingredient, at least one selected from a compound represented by the following formula (1), a salt thereof, and a hydrate thereof.
下記式（１）で表される化合物は少なくとも１個の不斉原子を有する。そのため、下記式（１）で表される化合物には少なくとも２種の光学異性体が存在する。本発明の体臭抑制剤は、下記式（１）で表される化合物として、光学異性体（若しくは、鏡像異性体）の等量混合物（＝ラセミ体）を使用してもよく、又前記光学異性体の等量混合物を光学分割して得られる光学活性体（若しくは、片方の鏡像異性体）を使用しても良い。尚、ラセミ体の光学分割にはジアステレオマー塩法やキラルカラムを用いた分割法等、周知慣用の方法を採用することができる。 The compound represented by the following formula (1) has at least one asymmetric atom. Therefore, the compound represented by the following formula (1) has at least two types of optical isomers. As the compound represented by the following formula (1), an equivalent mixture (= racemate) of optical isomers (or enantiomers) may be used as the compound represented by the following formula (1). An optically active substance (or one enantiomer) obtained by optically resolving a mixture of isomers may be used. For the optical resolution of the racemate, a known and commonly used method such as a diastereomer salt method or a resolution method using a chiral column can be employed.
前記Ｒ1、Ｒ2における炭化水素基には、脂肪族炭化水素基、脂環式炭化水素基、芳香族炭化水素基、及びこれらが単結合を介して結合した基が含まれる。 The hydrocarbon group for R 1 and R 2 includes an aliphatic hydrocarbon group, an alicyclic hydrocarbon group, an aromatic hydrocarbon group, and a group in which these are bonded via a single bond.
脂肪族炭化水素基としては、Ｃ1-20（＝炭素数１〜２０）の脂肪族炭化水素基が好ましく、例えば、メチル基、エチル基、プロピル基、イソプロピル基、ブチル基、イソブチル基、ｓ−ブチル基、ｔ−ブチル基、ペンチル基、ヘキシル基、デシル基、ドデシル基等の炭素数Ｃ1-20（好ましくはＣ1-10、特に好ましくはＣ1-3）程度のアルキル基；ビニル基、アリル基、１−ブテニル基等のＣ2-20（好ましくはＣ2-10、特に好ましくはＣ2-3）程度のアルケニル基；エチニル基、プロピニル基等のＣ2-20（好ましくはＣ2-10、特に好ましくはＣ2-3）程度のアルキニル基等が挙げられる。 As the aliphatic hydrocarbon group, a C 1-20 (= C 1-20 ) aliphatic hydrocarbon group is preferable, and examples thereof include a methyl group, an ethyl group, a propyl group, an isopropyl group, a butyl group, an isobutyl group, and an s group. An alkyl group having about C 1-20 (preferably C 1-10 , particularly preferably C 1-3 ) carbon atoms such as -butyl group, t-butyl group, pentyl group, hexyl group, decyl group and dodecyl group; vinyl; An alkenyl group of about C 2-20 (preferably C 2-10 , particularly preferably C 2-3 ) such as a group, allyl group, and 1-butenyl group; C 2-20 (preferably a ethynyl group or propynyl group) An alkynyl group of about C 2-10 , particularly preferably about C 2-3 ) is exemplified.
脂環式炭化水素基としては、Ｃ3-20脂環式炭化水素基が好ましく、例えば、シクロプロピル基、シクロブチル基、シクロペンチル基、シクロヘキシル基、シクロオクチル基等のＣ3-20（好ましくはＣ3-15、特に好ましくはＣ5-8）程度のシクロアルキル基；シクロペンテニル基、シクロへキセニル基等のＣ3-20（好ましくはＣ3-15、特に好ましくはＣ5-8）程度のシクロアルケニル基；パーヒドロナフタレン−１−イル基、ノルボルニル基、アダマンチル基、トリシクロ［５．２．１．０2,6］デカン−８−イル基、テトラシクロ［４．４．０．１2,5．１7,10］ドデカン−３−イル基等の橋かけ環式炭化水素基等が挙げられる。 As the alicyclic hydrocarbon group, a C 3-20 alicyclic hydrocarbon group is preferable, and for example, a C 3-20 (preferably C 3-20) such as a cyclopropyl group, a cyclobutyl group, a cyclopentyl group, a cyclohexyl group, and a cyclooctyl group is preferred. 3-15, especially preferably C 5-8) about a cycloalkyl group; cyclopentenyl group, C 3-20 (preferably C 3-15, such as cyclohexenyl group cycloheteroalkyl, particularly preferably C 5-8) about the cycloalkenyl group; perhydronaphthalene-1-yl group, a norbornyl group, an adamantyl group, a tricyclo [5.2.1.0 2,6] decan-8-yl group, tetracyclo [4.4.0.1 2, 5 ． [ 7,10 ] dodecane-3-yl group and the like.
芳香族炭化水素基としては、Ｃ6-14（特に、Ｃ6-10）芳香族炭化水素基が好ましく、例えば、フェニル基、ナフチル基等が挙げられる。 As the aromatic hydrocarbon group, a C 6-14 (particularly, C 6-10 ) aromatic hydrocarbon group is preferable, and examples thereof include a phenyl group and a naphthyl group.
脂肪族炭化水素基と脂環式炭化水素基とが結合した基には、シクロペンチルメチル基、シクロヘキシルメチル基、２−シクロヘキシルエチル基等のシクロアルキル置換アルキル基（例えば、Ｃ3-20シクロアルキル置換Ｃ1-4アルキル基等）等が含まれる。また、脂肪族炭化水素基と芳香族炭化水素基とが結合した基には、アラルキル基（例えば、Ｃ7-18アラルキル基等）、アルキル置換アリール基（例えば、１〜４個程度のＣ1-4アルキル基が置換したフェニル基又はナフチル基等）等が含まれる。 Examples of the group in which the aliphatic hydrocarbon group and the alicyclic hydrocarbon group are bonded include a cycloalkyl-substituted alkyl group such as a cyclopentylmethyl group, a cyclohexylmethyl group, and a 2-cyclohexylethyl group (for example, a C 3-20 cycloalkyl substitution group) C 1-4 alkyl group) and the like. Examples of the group in which the aliphatic hydrocarbon group and the aromatic hydrocarbon group are bonded include an aralkyl group (for example, a C 7-18 aralkyl group) and an alkyl-substituted aryl group (for example, about 1 to 4 C 1 -4 alkyl group-substituted phenyl group or naphthyl group).
前記Ｒ3における脂肪族炭化水素基としては、上記Ｒ1、Ｒ2における脂肪族炭化水素基と同様の例を挙げることができる。 Examples of the aliphatic hydrocarbon group for R 3 include the same examples as the aliphatic hydrocarbon group for R 1 and R 2 .
前記Ｒ3における脂肪族炭化水素基が有していてもよい置換基としては、例えば、ハロゲン原子、オキソ基、ヒドロキシル基、置換オキシ基（例えば、Ｃ1-4アルコキシ基、Ｃ6-10アリールオキシ基、Ｃ7-16アラルキルオキシ基、Ｃ1-4アシルオキシ基等）、カルボキシル基、置換オキシカルボニル基（例えば、Ｃ1-4アルコキシカルボニル基、Ｃ6-10アリールオキシカルボニル基、Ｃ7-16アラルキルオキシカルボニル基等）、置換又は無置換カルバモイル基（例えば、カルバモイル、メチルカルバモイル等のＣ1-4アルキル置換カルバモイル、フェニルカルバモイル基等のＣ6-10アリール置換カルバモイル基）、シアノ基、ニトロ基、置換又は無置換アミノ基（例えば、メチルアミノ、ジメチルアミノ、エチルアミノ、ジエチルアミノ基等のモノ又はジＣ1-4アルキルアミノ基；１−ピロリジニル、ピペリジノ、モルホリノ基等の５〜８員の環状アミノ基；アセチルアミノ、プロピオニルアミノ、ベンゾイルアミノ基等のＣ1-10アシルアミノ基；ベンゼンスルホニルアミノ、ｐ−トルエンスルホニルアミノ基等のスルホニルアミノ基）、スルホ基、複素環式基等が挙げられる。また、前記ヒドロキシル基やカルボキシル基は有機合成の分野で慣用の保護基で保護されていてもよい。 Examples of the substituent which the aliphatic hydrocarbon group for R 3 may have include, for example, a halogen atom, an oxo group, a hydroxyl group, a substituted oxy group (for example, a C 1-4 alkoxy group, a C 6-10 aryl) Oxy group, C 7-16 aralkyloxy group, C 1-4 acyloxy group, etc., carboxyl group, substituted oxycarbonyl group (for example, C 1-4 alkoxycarbonyl group, C 6-10 aryloxycarbonyl group, C 7- A substituted or unsubstituted carbamoyl group (eg, a C 1-4 alkyl-substituted carbamoyl such as carbamoyl or methylcarbamoyl, a C 6-10 aryl-substituted carbamoyl group such as a phenylcarbamoyl group), a cyano group, a nitro group Group, substituted or unsubstituted amino group (for example, mono- or Di-C 1-4 alkylamino group; 5- to 8-membered cyclic amino group such as 1-pyrrolidinyl, piperidino, morpholino group; C 1-10 acylamino group such as acetylamino, propionylamino, benzoylamino group; benzenesulfonylamino; a sulfonylamino group such as a p-toluenesulfonylamino group), a sulfo group, and a heterocyclic group. Further, the hydroxyl group and the carboxyl group may be protected with a protecting group commonly used in the field of organic synthesis.
ｎは１以上の整数を示し、例えば１〜１０の整数である。 n represents an integer of 1 or more, for example, an integer of 1 to 10.
式（１）で表される化合物としては、下記［Ｉ］［II］が含まれる。
［Ｉ］式（１）中のＯＲ1基とＯＲ2基が何れもＯＨ基である化合物（化合物（Ｉ））
［II］式（１）中のＯＲ1基とＯＲ2基の少なくとも一方が、ＯＨ基以外の基である化合物（化合物（II））
The compounds represented by the formula (1) include the following [I] and [II].
[I] Compound wherein both OR 1 and OR 2 groups in formula (1) are OH groups (compound (I))
[II] A compound in which at least one of the OR 1 group and the OR 2 group in the formula (1) is a group other than an OH group (compound (II))
化合物（Ｉ）の場合、ｎとしては、好ましくは２〜１０の整数、特に好ましくは２〜８の整数である。 In the case of the compound (I), n is preferably an integer of 2 to 10, particularly preferably an integer of 2 to 8.
化合物（II）の場合、ｎとしては、好ましくは１〜８の整数、特に好ましくは２〜６の整数である。 In the case of the compound (II), n is preferably an integer of 1 to 8, particularly preferably an integer of 2 to 6.
化合物（II）におけるＯＲ1基とＯＲ2基の組みあわせとしては、下記［II-i］〜［II-v］の組み合わせが好ましい。特に、式（１）中のｎが１又は２の場合は下記［II-i］〜［II-iv］の組み合わせが好ましく、式（１）中のｎが３以上の整数の場合は下記［II-v］の組み合わせが好ましい。 As the combination of the OR 1 group and the OR 2 group in the compound (II), the following combinations [II-i] to [II-v] are preferable. In particular, when n in the formula (1) is 1 or 2, a combination of the following [II-i] to [II-iv] is preferable, and when n in the formula (1) is an integer of 3 or more, the following [ II-v] is preferred.
［II-i］下記式（i-1）で表される基と下記式（i-2）で表される基の組み合わせ
［式（i-2）中、Ｒ5〜Ｒ7は、同一又は異なって、水素原子、置換基を有していてもよい脂肪族炭化水素基、置換基を有していてもよい芳香族炭化水素基、ハロゲン原子、−ＣＯＯＲ8、−ＣＯＮＲ8 2、−ＣＯＲ8、−ＯＣＯＲ8、−ＣＦ3、−ＣＮ、−ＳＲ8、−ＳＯＲ8、−ＳＯ2Ｒ8、−ＳＯ2ＮＲ8 2、−ＰＯ（ＯＲ8）2、及び−ＮＯ2からなる群より選択される基を示す。前記Ｒ8は、水素原子、アルキル基、又はアルケニル基を示す。Ｒ5〜Ｒ7から選択される２つの基は互いに結合して、式（i-2）で示される基において、これらの基が結合する炭素原子と共に、環を形成していてもよい］
[II-i] Combination of a group represented by the following formula (i-1) and a group represented by the following formula (i-2)
[In the formula (i-2), R 5 to R 7 are the same or different and are each a hydrogen atom, an aliphatic hydrocarbon group which may have a substituent, or an aromatic group which may have a substituent. hydrocarbon group, a halogen atom, -COOR 8, -CONR 8 2, -COR 8, -OCOR 8, -CF 3, -CN, -SR 8, -SOR 8, -SO 2 R 8, -SO 2 NR 8 2, -PO (oR 8) 2 , and represents a group selected from the group consisting of -NO 2. R 8 represents a hydrogen atom, an alkyl group, or an alkenyl group. Two groups selected from R 5 to R 7 may be bonded to each other to form a ring together with the carbon atom to which these groups are bonded in the group represented by the formula (i-2)]
前記脂肪族炭化水素基、芳香族炭化水素基としては、上述のＲ1、Ｒ2における脂肪族炭化水素基、芳香族炭化水素基と同様の例を挙げることができる。 Examples of the aliphatic hydrocarbon group and the aromatic hydrocarbon group include the same examples as the aliphatic hydrocarbon group and the aromatic hydrocarbon group in R 1 and R 2 described above.
前記複素環式基を構成する複素環には、芳香族性複素環及び非芳香族性複素環が含まれる。このような複素環としては、環を構成する原子に炭素原子と少なくとも１種のヘテロ原子（例えば、酸素原子、イオウ原子、窒素原子等）を有する３〜１０員環（好ましくは４〜６員環）、及びこれらの縮合環を挙げることができる。具体的には、ヘテロ原子として酸素原子を含む複素環（例えば、オキシラン環等の３員環；オキセタン環等の４員環；フラン環、テトラヒドロフラン環、オキサゾール環、イソオキサゾール環、γ−ブチロラクトン環等の５員環；４−オキソ−４Ｈ−ピラン環、テトラヒドロピラン環、モルホリン環等の６員環；ベンゾフラン環、イソベンゾフラン環、４−オキソ−４Ｈ−クロメン環、クロマン環、イソクロマン環等の縮合環；３−オキサトリシクロ［４．３．１．１4,8］ウンデカン−２−オン環、３−オキサトリシクロ［４．２．１．０4,8］ノナン−２−オン環等の橋かけ環）、ヘテロ原子としてイオウ原子を含む複素環（例えば、チオフェン環、チアゾール環、イソチアゾール環、チアジアゾール環等の５員環；４−オキソ−４Ｈ−チオピラン環等の６員環；ベンゾチオフェン環等の縮合環等）、ヘテロ原子として窒素原子を含む複素環（例えば、ピロール環、ピロリジン環、ピラゾール環、イミダゾール環、トリアゾール環等の５員環；イソシアヌル環、ピリジン環、ピリダジン環、ピリミジン環、ピラジン環、ピペリジン環、ピペラジン環等の６員環；インドール環、インドリン環、キノリン環、アクリジン環、ナフチリジン環、キナゾリン環、プリン環等の縮合環等）等が挙げられる。複素環式基は前記複素環の構造式から１個の水素原子を除いた基である。 The heterocyclic ring constituting the heterocyclic group includes an aromatic heterocyclic ring and a non-aromatic heterocyclic ring. As such a heterocyclic ring, a 3- to 10-membered ring (preferably a 4- to 6-membered) having a carbon atom and at least one kind of hetero atom (for example, an oxygen atom, a sulfur atom, a nitrogen atom, etc.) as atoms constituting the ring is preferred. Ring) and condensed rings thereof. Specifically, a heterocyclic ring containing an oxygen atom as a hetero atom (for example, a three-membered ring such as an oxirane ring; a four-membered ring such as an oxetane ring; a furan ring, a tetrahydrofuran ring, an oxazole ring, an isoxazole ring, and a γ-butyrolactone ring) 5-membered ring such as 4-oxo-4H-pyran ring, tetrahydropyran ring, morpholine ring and the like; benzofuran ring, isobenzofuran ring, 4-oxo-4H-chromene ring, chroman ring, isochroman ring and the like Condensed ring; 3-oxatricyclo [4.3.1.1 4,8 ] undecane-2-one ring, 3-oxatricyclo [4.2.1.0 4,8 ] nonan-2-one ring A 5-membered ring such as a thiophene ring, a thiazole ring, an isothiazole ring, and a thiadiazole ring; 4-oxo-4H-thio A 6-membered ring such as a pyran ring; a condensed ring such as a benzothiophene ring); a heterocyclic ring containing a nitrogen atom as a hetero atom (eg, a 5-membered ring such as a pyrrole ring, a pyrrolidine ring, a pyrazole ring, an imidazole ring, a triazole ring; 6-membered ring such as isocyanuric ring, pyridine ring, pyridazine ring, pyrimidine ring, pyrazine ring, piperidine ring, piperazine ring; condensed ring such as indole ring, indoline ring, quinoline ring, acridine ring, naphthyridine ring, quinazoline ring and purine ring Etc.). The heterocyclic group is a group obtained by removing one hydrogen atom from the structural formula of the heterocyclic ring.
前記Ｒ4〜Ｒ7における脂肪族炭化水素基、芳香族炭化水素基、及び複素環式基が有していてもよい置換基としては、前記Ｒ3における脂肪族炭化水素基が有していてもよい置換基と同様の例を挙げることができる。 As the substituent which the aliphatic hydrocarbon group, aromatic hydrocarbon group, and heterocyclic group for R 4 to R 7 may have, the aliphatic hydrocarbon group for R 3 has Examples of the substituent may be the same as those described above.
［II-ii］下記式（ii-1）で表される基と下記式（ii-2）で表される基の組み合わせ
で表される基を示す］
［式（ii-2）中、Ｙ1は水素原子、アルキル基、アルケニル基、アルコキシ基、アルケニルオキシ基、ハロゲン原子、−ＣＯＯＲ8、−ＣＯＮＲ8 2、−ＣＯＲ8、−ＯＣＯＲ8、−ＣＦ3、−ＣＮ、−ＳＲ8、−ＳＯＲ8、−ＳＯ2Ｒ8、−ＳＯ2ＮＲ8 2、−ＰＯ（ＯＲ8）2、及び−ＮＯ2からなる群より選択される基を示す。Ｒ8は前記に同じ。Ｙ2は水素原子、置換基を有していてもよいアルキル基、置換基を有していてもよいアルケニル基、−ＣＯＯＲ3、−ＣＯＮＲ3 2、−ＣＯＲ3、−ＣＮ、−ＮＯ2、−ＮＨＣＯＲ3、−ＯＲ3、−ＳＲ3、−ＯＣＯＲ3、−ＳＯ3Ｒ3、及び−ＳＯ2ＮＲ3 2からなる群より選択される基（前記Ｒ3は、前記に同じ）を示す。Ｙ1とＹ2は互いに結合して、式（ii-2）中のベンゼン環を構成する炭素原子と共に、環を形成していてもよい］
[II-ii] Combination of a group represented by the following formula (ii-1) and a group represented by the following formula (ii-2)
Represents a group represented by
Wherein (ii-2), Y 1 is a hydrogen atom, an alkyl group, an alkenyl group, an alkoxy group, an alkenyloxy group, a halogen atom, -COOR 8, -CONR 8 2, -COR 8, -OCOR 8, -CF 3 shows -CN, -SR 8, -SOR 8, -SO 2 R 8, -SO 2 NR 8 2, -PO (oR 8) 2, and a group selected from the group consisting of -NO 2. R 8 is the same as above. Y 2 is a hydrogen atom, an optionally substituted alkyl group, alkenyl group which may have a substituent group, -COOR 3, -CONR 3 2, -COR 3, -CN, -NO 2, -NHCOR 3, -OR 3, -SR 3 , -OCOR 3, -SO 3 R 3, and -SO 2 NR 3 2 consisting of groups selected from the group (wherein R 3 is as defined above) shows a. Y 1 and Y 2 may be bonded to each other to form a ring together with the carbon atoms constituting the benzene ring in formula (ii-2).
［II-iii］置換基を有していてもよいアルコキシ基と、下記式（iii-1）〜（iii-4）で表される基から選択される基の組み合わせ
［II-iv］ＯＲ1基とＯＲ2基が、同一又は異なって、下記式（iv-1）で表される基である組み合わせ
［II-v］ヒドロキシル基と置換基を有していてもよい脂肪族炭化水素オキシ基（好ましくはＣ1-6アルコキシ基）との組み合わせ [II-v] Combination of a hydroxyl group and an optionally substituted aliphatic hydrocarbonoxy group (preferably a C 1-6 alkoxy group)
上記アルキル基、アルケニル基、アリール基、アルコキシ基、及び脂肪族炭化水素オキシ基が有していてもよい置換基としては、前記Ｒ3における脂肪族炭化水素基が有していてもよい置換基と同様の例を挙げることができる。 Examples of the substituent that the alkyl group, alkenyl group, aryl group, alkoxy group, and aliphatic hydrocarbonoxy group may have include substituents that the aliphatic hydrocarbon group for R 3 may have. The same example as described above can be given.
前記脂肪族炭化水素オキシ基を構成する脂肪族炭化水素基としては、上記Ｒ1、Ｒ2における脂肪族炭化水素基と同様の例を挙げることができる。 Examples of the aliphatic hydrocarbon group constituting the aliphatic hydrocarbon oxy group include the same examples as the aliphatic hydrocarbon group for R 1 and R 2 .
前記化合物（Ｉ）としては、下記式（I-1）〜（I-5）で表される化合物（光学異性体を含む）が好ましい。
前記化合物（II）としては、下記式（II-1）〜（II-2）で表される化合物（光学異性体を含む）が好ましい。
式（１）で表される化合物は水和物であってもよく、又、式（１）で表される化合物やその水和物は塩を形成していてもよい。式（１）で表される化合物やその水和物の塩としては、例えば、ナトリウム塩、カリウム塩等のアルカリ金属塩；マグネシウム塩、カルシウム塩、バリウム塩等のアルカリ土類金属塩；アンモニアとの塩；トリメチルアミン、トリエチルアミン、トリブチルアミン、ピリジン、キノリン、ピペリジン、イミダゾール、ピコリン、ジメチルアミノピリジン、Ｎ，Ｎ−ジメチルアニリン、Ｎ−メチルピペリジン、Ｎ−メチルモルホリン、ジエチルアミン、シクロヘキシルアミン、プロカイン、ジベンジルアミン、Ｎ−ベンジル−β−フェネチルアミン、１−エフェナミン、Ｎ，Ｎ’−ジベンジルエチレンジアミン、Ｎ−メチル−Ｄ−グルカミン等の含窒素有機塩基との塩；リジン、アルギニン、オルニチン等の塩基性アミノ酸との塩；遷移金属塩；塩酸、硫酸、硝酸、リン酸、ホウ酸等の無機酸との塩；シュウ酸、酢酸、ｐ−トルエンスルホン酸等の有機酸との塩等が挙げられる。 The compound represented by the formula (1) may be a hydrate, and the compound represented by the formula (1) or a hydrate thereof may form a salt. Examples of the salt of the compound represented by the formula (1) or a hydrate thereof include alkali metal salts such as sodium salt and potassium salt; alkaline earth metal salts such as magnesium salt, calcium salt and barium salt; Salts of trimethylamine, triethylamine, tributylamine, pyridine, quinoline, piperidine, imidazole, picoline, dimethylaminopyridine, N, N-dimethylaniline, N-methylpiperidine, N-methylmorpholine, diethylamine, cyclohexylamine, procaine, dibenzyl Salts with nitrogen-containing organic bases such as amine, N-benzyl-β-phenethylamine, 1-ephenamine, N, N′-dibenzylethylenediamine, N-methyl-D-glucamine; basic amino acids such as lysine, arginine and ornithine And transition metal salts Hydrochloric, sulfuric, nitric, phosphoric acid, salts with inorganic acids such as boric acid; oxalic acid, acetic acid, salts with organic acids such as p- toluenesulfonic acid.
上記式（１）で表される化合物のうち化合物（Ｉ）は、例えば下記工程［１］〜［４］を経て製造することができる。また、化合物（II）は、例えば下記工程［１］〜［１０］を経て製造することができる。 Compound (I) among the compounds represented by the above formula (1) can be produced, for example, through the following steps [1] to [4]. Compound (II) can be produced, for example, through the following steps [1] to [10].
下記式中、ｎは前記に同じ。Ｘはハロゲン原子（フッ素原子、塩素原子、臭素原子、又はヨウ素原子）を示し、Ｒ、Ｒ’は、同一又は異なって、炭素数１〜１０のアルキル基を示す。Ｒ”はアミノ基の保護基を示す。ＤＰＲは脱保護剤を示す。尚、アミノ基の保護基としては、例えば、炭素数１〜１０のアルキル基、炭素数７〜１８のアラルキル基、アシル基（ＲaＣ（＝Ｏ）基；Ｒaは炭素数１〜１０のアルキル基）、アルコキシカルボニル基（ＲbＯＣ（＝Ｏ）基；Ｒbは炭素数１〜１０のアルキル基）、置換基を有していても良いベンジルオキシカルボニル基、置換基を有していても良いフェニルメチリデン基、置換基を有していても良いジフェニルメチリデン基等が挙げられる。また、前記置換基としては、例えば、ハロゲン原子、炭素数１〜３のアルコキシ基、ニトロ基等が挙げられる。 In the following formula, n is the same as described above. X represents a halogen atom (a fluorine atom, a chlorine atom, a bromine atom, or an iodine atom), and R and R ′ are the same or different and represent an alkyl group having 1 to 10 carbon atoms. R ″ represents an amino-protecting group. DPR represents a deprotecting agent. Examples of the amino-protecting group include an alkyl group having 1 to 10 carbon atoms, an aralkyl group having 7 to 18 carbon atoms, and an acyl group. group (R a C (= O) group; R a is an alkyl group having 1 to 10 carbon atoms), an alkoxycarbonyl group (R b OC (= O) group; R b represents an alkyl group having 1 to 10 carbon atoms), A benzyloxycarbonyl group which may have a substituent, a phenylmethylidene group which may have a substituent, a diphenylmethylidene group which may have a substituent, and the like. Examples of the group include a halogen atom, an alkoxy group having 1 to 3 carbon atoms, a nitro group, and the like.
工程［１］の反応は、式（２）で表されるジハロゲン化アルキレンに、式（３）で表される亜リン酸エステルを反応させて、式（４）で表されるホスホノアルカン酸を得る反応（ミカエリス・アルブゾフ反応；Michaelis-Arbuzov Reaction）である。前記式（３）で表される亜リン酸エステルの使用量は、式（２）で表されるジハロゲン化アルキレン１モルに対して、例えば０．１〜１．０モル程度である。 In the reaction of the step [1], the dialkylene halide represented by the formula (2) is reacted with a phosphite represented by the formula (3), and the phosphonoalkanoic acid represented by the formula (4) is reacted. (Michaelis-Arbuzov Reaction). The used amount of the phosphite represented by the formula (3) is, for example, about 0.1 to 1.0 mol based on 1 mol of the alkylene dihalide represented by the formula (2).
工程［１］の反応の反応温度は、例えば１３０〜１４０℃程度が好ましい。反応時間は、例えば０．５〜２時間程度である。 The reaction temperature of the reaction in the step [1] is preferably, for example, about 130 to 140 ° C. The reaction time is, for example, about 0.5 to 2 hours.
工程［２］の反応は、工程［１］の反応を経て得られた式（４）で表されるホスホノアルカン酸に、式（５）で表される化合物を反応させて、式（６）で表される化合物を得る反応である。前記式（５）で表される化合物の使用量は、式（４）で表されるホスホノアルカン酸１モルに対して、例えば０．７〜１．３モル程度である。 In the reaction of the step [2], the compound represented by the formula (5) is reacted with the phosphonoalkanoic acid represented by the formula (4) obtained through the reaction of the step [1] to give a compound represented by the formula (6). This is a reaction for obtaining the compound represented by the formula (1). The amount of the compound represented by the formula (5) is, for example, about 0.7 to 1.3 mol per 1 mol of the phosphonoalkanoic acid represented by the formula (4).
工程［２］の反応は、塩基の存在下で行うことが、反応の進行を促進する効果が得られる点で好ましい。前記塩基としては、例えば、炭酸水素カリウム、炭酸水素ナトリウム、炭酸カリウム、炭酸ナトリウム等の炭酸塩類（特にアルカリ金属の炭酸塩類）；水酸化ナトリウム、水酸化カリウム等のアルカリ金属の水酸化物；水酸化カルシウム、水酸化マグネシウム等のアルカリ土類金属の水酸化物；リン酸二水素ナトリウムやリン酸二水素カリウム等のリン酸塩類（特にアルカリ金属のリン酸塩類）；酢酸ナトリウムや酢酸カリウム等のカルボン酸塩類（特にアルカリ金属のカルボン酸塩類）；トリエチルアミン、ピリジン等の有機塩基類；ナトリウムメトキシド、ナトリウムエトキシド等の金属アルコキシド類（特にアルカリ金属のアルコキシ類）；水素化ナトリウム等の金属水素化物類等が挙げられる。これらは１種を単独で、又は２種以上を組み合わせて使用することができる。塩基の使用量は、式（４）で表されるホスホノアルカン酸１モルに対して、例えば０．９〜１．１モル程度である。 The reaction in step [2] is preferably performed in the presence of a base, since an effect of accelerating the progress of the reaction can be obtained. Examples of the base include carbonates such as potassium hydrogen carbonate, sodium hydrogen carbonate, potassium carbonate and sodium carbonate (particularly, alkali metal carbonates); hydroxides of alkali metals such as sodium hydroxide and potassium hydroxide; and water. Hydroxides of alkaline earth metals such as calcium oxide and magnesium hydroxide; phosphates (especially alkali metal phosphates) such as sodium dihydrogen phosphate and potassium dihydrogen phosphate; Carboxylates (especially alkali metal carboxylates); organic bases such as triethylamine and pyridine; metal alkoxides such as sodium methoxide and sodium ethoxide (especially alkali metal alkoxys); metal hydrogen such as sodium hydride And the like. These can be used alone or in combination of two or more. The amount of the base used is, for example, about 0.9 to 1.1 mol per 1 mol of the phosphonoalkanoic acid represented by the formula (4).
工程［２］の反応は溶媒の存在下で行うことが好ましい。前記溶媒としては、例えば、アセトン、エチルメチルケトン等のケトン類；テトラヒドロフラン、ジオキサン等のエーテル類；アセトニトリル等のニトリル類；ジメチルスルホキシド等のスルホキシド類；スルホラン等のスルホン類；酢酸エチル等のエステル類；ジメチルホルムアミド等のアミド類；メタノール、エタノール、ｔ−ブタノール等のアルコール類；ペンタン、ヘキサン、石油エーテル等の炭化水素類；ベンゼン、トルエン、キシレン等の芳香族炭化水素類；塩化メチレン、クロロホルム、ブロモホルム、クロロベンゼン、ブロモベンゼン等の含ハロゲン化合物；ジメチルカーボネート、ジエチルカーボネート、エチルメチルカーボネート等の鎖状カーボネート；エチレンカーボネート、プロピレンカーボネート等の環状カーボネート等が挙げられる。これらは１種を単独で、又は２種以上を組み併せて使用することができる。 The reaction in step [2] is preferably performed in the presence of a solvent. Examples of the solvent include ketones such as acetone and ethyl methyl ketone; ethers such as tetrahydrofuran and dioxane; nitriles such as acetonitrile; sulfoxides such as dimethyl sulfoxide; sulfones such as sulfolane; esters such as ethyl acetate. Amides such as dimethylformamide; alcohols such as methanol, ethanol and t-butanol; hydrocarbons such as pentane, hexane and petroleum ether; aromatic hydrocarbons such as benzene, toluene and xylene; methylene chloride, chloroform; Halogen-containing compounds such as bromoform, chlorobenzene and bromobenzene; linear carbonates such as dimethyl carbonate, diethyl carbonate and ethyl methyl carbonate; cyclic carbonates such as ethylene carbonate and propylene carbonate Over doors and the like. These can be used alone or in combination of two or more.
工程［２］の反応の反応温度は、例えば１００〜１１０℃程度が好ましい。反応時間は、例えば６〜２４時間程度である。 The reaction temperature of the reaction in the step [2] is preferably, for example, about 100 to 110 ° C. The reaction time is, for example, about 6 to 24 hours.
工程［３］の反応は、工程［２］の反応を経て得られた式（６）で表される化合物の保護基で保護されたカルボキシ基（−ＣＯＯＲ’）、及び保護基で保護されたアミノ基（−ＮＨＲ"）、及び保護基で保護されたホスホン酸基（−Ｐ（＝Ｏ）（ＯＲ）2）を脱保護して、式（７）で表される化合物を得る反応である。保護基で保護された基の脱保護は、脱保護剤を反応させることにより行うことができる。前記脱保護剤（上記式中では、「ＤＰＲ」で表される）としては、強塩基（例えば、水酸化ナトリウム）又は強酸（例えば、塩酸）を好適に使用することができる。 In the reaction of the step [3], the compound represented by the formula (6) obtained through the reaction of the step [2] was protected with a carboxy group (—COOR ′) protected with a protecting group, and with a protecting group. Deprotection of an amino group (—NHR ″) and a phosphonic acid group (—P (＝ O) (OR) 2 ) protected by a protecting group to obtain a compound represented by the formula (7). The deprotection of the group protected by the protecting group can be performed by reacting a deprotecting agent, wherein the deprotecting agent (represented by “DPR” in the above formula) includes a strong base ( For example, sodium hydroxide) or a strong acid (eg, hydrochloric acid) can be suitably used.
工程［３］の反応の反応温度は、例えば９０〜１００℃程度が好ましい。反応時間は、例えば２０〜２４時間程度である。 The reaction temperature of the reaction in the step [3] is preferably, for example, about 90 to 100 ° C. The reaction time is, for example, about 20 to 24 hours.
工程［４］の反応は、工程［３］の反応を経て得られた式（７）で表される化合物に、脱保護剤をトラップする作用を有する化合物を反応させて、化合物（Ｉ）を得る反応である。脱保護剤をトラップする作用を有する化合物としては、例えば脱保護剤が塩酸である場合は、プロピレンオキシドを使用することができる。脱保護剤をトラップする作用を有する化合物の使用量は、式（７）で表される化合物１モルに対して、例えば３．０〜６．０モル程度である。 In the reaction of the step [4], the compound represented by the formula (7) obtained through the reaction of the step [3] is reacted with a compound having an action of trapping a deprotecting agent to convert the compound (I). It is a reaction to get. As the compound having an action of trapping the deprotecting agent, for example, when the deprotecting agent is hydrochloric acid, propylene oxide can be used. The amount of the compound having the function of trapping the deprotecting agent is, for example, about 3.0 to 6.0 mol per 1 mol of the compound represented by the formula (7).
工程［５］は、化合物（Ｉ）のカルボキシル基に保護基を導入する工程であり、例えば、化合物（Ｉ）とＲCＯＨ（ＲCは置換基を有していてもよいアリール基又はアラルキル基を示し、好ましくはベンジル、４−ニトロベンジル基である）を反応させることにより保護基を導入することができる。この反応は、酸触媒（例えば、塩酸等）の存在下、室温付近の温度環境下で行うことが好ましい。反応時間は、例えば１２〜２４時間程度である。 Step [5] is a step of introducing a protecting group into the carboxyl group of compound (I). For example, compound (I) and R C OH (where R C is an aryl group or aralkyl which may have a substituent) A protecting group can be introduced by reacting a benzyl group, preferably a benzyl or 4-nitrobenzyl group. This reaction is preferably performed in the presence of an acid catalyst (for example, hydrochloric acid or the like) in a temperature environment near room temperature. The reaction time is, for example, about 12 to 24 hours.
工程［６］は、化合物（Ｉ）のアミノ基に保護基を導入する工程であり、例えば、溶媒に溶解した化合物（Ｉ）中にＲ”Ｘを滴下して反応させることにより、保護基を導入することができる。この反応は、塩基（例えば、炭酸水素ナトリウム等）の存在下で行うことが好ましい。 Step [6] is a step of introducing a protecting group into the amino group of compound (I). For example, the protecting group is added by dropping R ″ X into compound (I) dissolved in a solvent and reacting. This reaction is preferably carried out in the presence of a base (for example, sodium bicarbonate or the like).
前記溶媒としては、例えば、水、ハロゲン化炭化水素系溶媒、飽和又は不飽和炭化水素系溶媒、芳香族炭化水素系溶媒、エーテル系溶媒等を１種又は２種以上使用することができる。 As the solvent, for example, one or more of water, a halogenated hydrocarbon solvent, a saturated or unsaturated hydrocarbon solvent, an aromatic hydrocarbon solvent, an ether solvent, and the like can be used.
滴下時温度は、室温以下が好ましく、特に０℃付近が好ましい。反応時間は、例えば０．５〜２時間程度である。また、滴下終了後は例えば２５〜３０℃に保温した状態で、例えば１０〜２４時間程度、撹拌しつつ熟成させることが好ましい。 The temperature at the time of dropping is preferably room temperature or lower, particularly preferably around 0 ° C. The reaction time is, for example, about 0.5 to 2 hours. After completion of the dropping, it is preferable to ripen the mixture while stirring, for example, for about 10 to 24 hours while keeping the temperature at 25 to 30 ° C.
工程［７］は、リン酸基の２つのヒドロキシル基をハロゲン原子で置換する工程であり、例えば、工程［５］［６］を経て得られた化合物に、触媒及び溶媒の存在下でハロゲン化剤を反応させることにより行うことができる。前記触媒としては、例えば、Ｎ，Ｎ−ジメチルホルムアミド等を使用することができる。また、前記溶媒としては、ハロゲン化炭化水素系溶媒、エーテル系溶媒等を１種又は２種以上使用することができる。前記ハロゲン化剤としては、例えば、塩酸オキサリル、塩化チオニル、五塩化リン、オキシ塩化リン等が挙げられる。これらは１種を単独で、又は２種以上を組み合わせて使用することができる。この反応は、室温付近の温度で１時間程度行うことが好ましい。 Step [7] is a step of substituting two hydroxyl groups of a phosphate group with a halogen atom. For example, the compound obtained through steps [5] and [6] is halogenated in the presence of a catalyst and a solvent. The reaction can be carried out by reacting an agent. As the catalyst, for example, N, N-dimethylformamide and the like can be used. Further, as the solvent, one or more halogenated hydrocarbon solvents, ether solvents and the like can be used. Examples of the halogenating agent include oxalyl hydrochloride, thionyl chloride, phosphorus pentachloride, phosphorus oxychloride and the like. These can be used alone or in combination of two or more. This reaction is preferably performed at a temperature near room temperature for about one hour.
工程［８］は、Ｒ1ＯＨを反応させて、工程［７］を経て得られたリン原子に結合するハロゲン原子の一方をＯＲ1に置換する工程である。この反応は塩基の存在下で行うことが好ましく、塩基としては、例えば、トリエチルアミン、トリブチルアミン、ジイソプロピルエチルアミン、Ｎ−メチルピペリジン、Ｎ−メチルモルホリン、ジエチルイソプロピルアミン、Ｎ−メチルイミダゾール、ピリジン等が挙げられる。また、この反応は溶媒の存在下で行うことが好ましく、溶媒としては乾燥ジクロロメタンを使用することが好ましい。反応は、−６５℃付近で３０分間程度撹拌した後、室温までゆっくり昇温し、その後室温を保持した状態で１〜３時間程撹拌して行うことが好ましい。 Step [8] is a step of reacting R 1 OH to replace one of the halogen atoms bonded to the phosphorus atom obtained through step [7] with OR 1 . This reaction is preferably performed in the presence of a base. Examples of the base include triethylamine, tributylamine, diisopropylethylamine, N-methylpiperidine, N-methylmorpholine, diethylisopropylamine, N-methylimidazole, pyridine and the like. Can be This reaction is preferably performed in the presence of a solvent, and it is preferable to use dry dichloromethane as the solvent. The reaction is preferably stirred at about -65 ° C for about 30 minutes, then slowly heated to room temperature, and then stirred for about 1 to 3 hours while maintaining the room temperature.
工程［９］は、Ｒ2ＯＨを反応させて、リン原子に結合するハロゲン原子の他方をＯＲ2に置換する工程である。工程［９］は、Ｒ1ＯＨに代えてＲ2ＯＨを使用する以外は工程［８］と同様の方法で行うことができる。 Step [9] is a step of reacting R 2 OH to replace the other of the halogen atoms bonded to the phosphorus atom with OR 2 . Step [9] can be performed in the same manner as in step [8] except that R 2 OH is used instead of R 1 OH.
工程［１０］は、保護基で保護されたカルボキシル基とアミノ基を脱保護する工程であり、例えば、接触水素還元法、塩化アルミニウムを用いた脱保護法等により行うことができる。前記接触水素還元法は、パラジウムを活性炭や硫酸バリウム等の担体に担持させたパラジウム系触媒や白金系触媒の存在下で、水素ガスをバブリングする方法である。また、前記塩化アルミニウムを用いた脱保護法は、三塩化アルミニウムを加えた溶媒（例えば、乾燥ニトロメタン等の高極性溶媒）で、工程［９］を経て得られた化合物とアニソールとを反応させる方法である。 Step [10] is a step of deprotecting a carboxyl group and an amino group protected by a protecting group, and can be performed by, for example, a catalytic hydrogen reduction method, a deprotection method using aluminum chloride, or the like. The catalytic hydrogen reduction method is a method in which hydrogen gas is bubbled in the presence of a palladium-based catalyst or a platinum-based catalyst in which palladium is supported on a carrier such as activated carbon or barium sulfate. The deprotection method using aluminum chloride is a method of reacting the compound obtained through step [9] with anisole in a solvent to which aluminum trichloride is added (for example, a highly polar solvent such as dry nitromethane). It is.
各工程の反応雰囲気としては反応を阻害しない限り特に限定されず、例えば、空気雰囲気、窒素雰囲気、アルゴン雰囲気等の何れであってもよい。また、反応は常圧、減圧又は加圧下で行なうことができる。更に、反応はバッチ式、セミバッチ式、連続式等の何れの方法でも行うことができる。 The reaction atmosphere in each step is not particularly limited as long as the reaction is not hindered, and may be, for example, any of an air atmosphere, a nitrogen atmosphere, and an argon atmosphere. The reaction can be carried out under normal pressure, reduced pressure or increased pressure. Further, the reaction can be performed by any method such as a batch system, a semi-batch system, and a continuous system.
各工程終了後は、得られた反応生成物に、例えば、ろ過、濃縮、蒸留、抽出、晶析、吸着、再結晶、カラムクロマトグラフィー等の分離手段や、これらを組み合わせた分離手段を施して精製してもよい。 After completion of each step, the obtained reaction product is subjected to, for example, filtration, concentration, distillation, extraction, crystallization, adsorption, recrystallization, separation means such as column chromatography, or a separation means combining these. It may be purified.
式（１）で表される化合物の水和物は、上記方法で得られた化合物（Ｉ）又は化合物（II）を、水と水溶性溶媒とを用いた晶析処理に付すことにより製造することができる。 The hydrate of the compound represented by the formula (1) is produced by subjecting the compound (I) or the compound (II) obtained by the above method to a crystallization treatment using water and a water-soluble solvent. be able to.
前記水溶性溶媒としては、室温（２５℃）において水に溶解する有機溶媒が好ましく、水に対する溶解度が５０％以上（好ましくは８０％以上、特に好ましくは９５以上）のものが好ましい。 The water-soluble solvent is preferably an organic solvent that dissolves in water at room temperature (25 ° C.), and preferably has a solubility in water of 50% or more (preferably 80% or more, particularly preferably 95 or more).
前記水溶性溶媒としては、アルコール（例えば、メタノール、エタノール等の炭素数１〜５の低級アルコール）を使用することが好ましい。 As the water-soluble solvent, it is preferable to use an alcohol (for example, a lower alcohol having 1 to 5 carbon atoms such as methanol and ethanol).
式（１）で表される化合物の塩は、上記方法で得られた化合物（Ｉ）又は化合物（II）に、例えば、水酸化ナトリウム、水酸化カリウム、水酸化マグネシウム、水酸化カルシウム、水酸化バリウム等の塩基性化合物；アンモニア；トリメチルアミン、トリエチルアミン、トリブチルアミン、ピリジン、キノリン、ピペリジン、イミダゾール、ピコリン、ジメチルアミノピリジン、Ｎ，Ｎ−ジメチルアニリン、Ｎ−メチルピペリジン、Ｎ−メチルモルホリン、ジエチルアミン、シクロヘキシルアミン、プロカイン、ジベンジルアミン、Ｎ−ベンジル−β−フェネチルアミン、１−エフェナミン、Ｎ，Ｎ’−ジベンジルエチレンジアミン、Ｎ−メチル−Ｄ−グルカミン等の含窒素有機塩基；リジン、アルギニン、オルニチン等の塩基性アミノ酸；塩酸、硫酸、硝酸、リン酸、ホウ酸等の無機酸；シュウ酸、酢酸、ｐ−トルエンスルホン酸等の有機酸等を反応させることにより製造することができる。 The salt of the compound represented by the formula (1) may be added to the compound (I) or the compound (II) obtained by the above method, for example, sodium hydroxide, potassium hydroxide, magnesium hydroxide, calcium hydroxide, hydroxide Basic compounds such as barium; ammonia; trimethylamine, triethylamine, tributylamine, pyridine, quinoline, piperidine, imidazole, picoline, dimethylaminopyridine, N, N-dimethylaniline, N-methylpiperidine, N-methylmorpholine, diethylamine, cyclohexyl Nitrogen-containing organic bases such as amine, procaine, dibenzylamine, N-benzyl-β-phenethylamine, 1-ephenamine, N, N′-dibenzylethylenediamine, N-methyl-D-glucamine; lysine, arginine, ornithine Basic amino acid; salt It can be produced by reacting an inorganic acid such as acid, sulfuric acid, nitric acid, phosphoric acid and boric acid; and an organic acid such as oxalic acid, acetic acid and p-toluenesulfonic acid.
式（１）で表される化合物は少なくとも１個の不斉原子を有する。例えば、式（１）で表される化合物が１個の不斉原子を有する場合、式（１）で表される化合物は２種の光学異性体の等量混合物（＝ラセミ体）である。ラセミ体の光学分割にはジアステレオマー塩法やキラルカラムを用いた分割法等、周知慣用の方法を採用することができる。 The compound represented by the formula (1) has at least one asymmetric atom. For example, when the compound represented by the formula (1) has one asymmetric atom, the compound represented by the formula (1) is an equal mixture (= racemate) of two optical isomers. For the optical resolution of the racemate, known and commonly used methods such as a diastereomer salt method and a resolution method using a chiral column can be employed.
ジアステレオマー塩法では、ラセミ体に塩基性光学活性物質を反応させて２種のジアステレオマー塩を形成させ、これらの溶解度の差を利用して分別晶析することにより一方のジアステレオマー塩を容易に単離することができる。 In the diastereomer salt method, two diastereomeric salts are formed by reacting a racemic form with a basic optically active substance, and fractional crystallization is carried out by utilizing the difference in solubility between the two to form one diastereomer. The salt can be easily isolated.
前記塩基性光学活性化合物としては、例えば、Ｄ−又はＬ−リジン、Ｄ−又はＬ−アルギニン、Ｄ−又はＬ−ｐ−ヒドロキシフェニルグリシンヒドラジド、Ｄ−又はＬ−ｐ−ヒドロキシフェニルグリシンメチルエステル等が挙げられる。 Examples of the basic optically active compound include D- or L-lysine, D- or L-arginine, D- or Lp-hydroxyphenylglycine hydrazide, D- or Lp-hydroxyphenylglycine methyl ester, and the like. Is mentioned.
また、単離された一方のジアステレオマー塩を、例えばイオン交換樹脂を用いて分解することにより、式（１）で表される化合物に含まれる２種の光学異性体の一方を単離することができる。前記イオン交換樹脂としては、酸性陽イオン交換樹脂が好ましく、例えば、商品名「アンバーライトＩＲ−１２０Ｂ」（オルガノ（株）製）、商品名「ダイヤイオン」（三菱化学（株）製）等を使用することができる。 Further, one of the two diastereoisomers contained in the compound represented by the formula (1) is isolated by decomposing one of the isolated diastereomeric salts using, for example, an ion exchange resin. be able to. As the ion exchange resin, an acidic cation exchange resin is preferable. Examples of the ion exchange resin include “Amberlite IR-120B” (manufactured by Organo Corporation) and “Diaion” (manufactured by Mitsubishi Chemical Corporation). Can be used.
本発明の体臭抑制剤は、有効成分として、上記式（１）で表される化合物［例えば化合物（Ｉ）及び／又は化合物（II）、好ましくは上記式（I-1）〜（I-5）（II-1）〜（II-2）で表される化合物］、その塩、及びそれらの水和物から選択される少なくとも１種（光学異性体を含む）を含む。 The body odor suppressant of the present invention comprises, as an active ingredient, a compound represented by the above formula (1) [for example, the compound (I) and / or the compound (II), preferably the above formulas (I-1) to (I-5). ) (II-1) to (II-2)], salts thereof, and hydrates thereof (including optical isomers).
本発明の体臭抑制剤は、皮膚表面に適用することにより、γ−グルタミルトランスペプチダーゼを阻害し、グルタチオンの代謝を抑制することにより、グルタチオンの原料であるシステインの供給を滞らせ、その結果としてグルタチオンの再合成を滞らせて、一時的にグルタチオン濃度を低下させる。そして、グルタチオン濃度の低下を引き金としてグルタチオンの産生を促進する。本発明の体臭抑制剤は、上記の作用機序によってグルタチオンの産生を促進する効果を発揮して、表皮細胞中のグルタチオン濃度を、本発明の体臭抑制剤を適用しない場合に比べて有意に上昇させることができる。 The body odor suppressant of the present invention, when applied to the skin surface, inhibits γ-glutamyl transpeptidase and suppresses metabolism of glutathione, thereby delaying the supply of cysteine, a raw material of glutathione, and consequently glutathione Slows down glutathione concentration by delaying the resynthesis of Then, the production of glutathione is promoted by a decrease in glutathione concentration. The body odor suppressant of the present invention exerts the effect of promoting the production of glutathione by the above-mentioned mechanism of action, and significantly increases the glutathione concentration in epidermal cells as compared with the case where the body odor suppressant of the present invention is not applied. Can be done.
そして、グルタチオンは、抗酸化作用、解毒作用、細胞賦活作用等を発揮して、体臭の原因物質の産生を抑制する効果を発揮する。例えば、腋臭や足臭の主な原因物質であるイソ吉草酸、ノナン酸、カプリン酸等の低級脂肪酸は、汗腺や皮脂腺からの分泌物を皮膚常在菌が分解することにより発生するが、グルタチオンは前記皮膚常在菌による分泌物の分解を抑制する効果を示すことにより、結果として腋臭や足臭の原因物質の産生を抑制する。また、加齢臭の主な原因物質である２−オクテナールや２−ノネナール等の不飽和アルデヒドは、加齢により皮脂中において含有比率が高まるパルミトレイン酸がその原料であるが、グルタチオンは皮膚細胞を賦活化して若返らせ、パルミトレイン酸の含有比率を低減する効果を示すことにより、結果として加齢臭の原因物質の産生を抑制する。 Glutathione exerts an antioxidant effect, a detoxifying effect, a cell activating effect, and the like, and exerts an effect of suppressing production of a substance causing body odor. For example, lower fatty acids such as isovaleric acid, nonanoic acid, and capric acid, which are main causes of axillary odor and foot odor, are generated by the resident bacteria decomposing secretions from sweat glands and sebaceous glands. Has an effect of suppressing the decomposition of secretions by the indigenous bacteria of the skin, thereby suppressing the production of substances causing axillary odor and foot odor. In addition, unsaturated aldehydes such as 2-octenal and 2-nonenal, which are the main causes of the aging odor, are palmitoleic acid whose content in sebum increases with aging, and glutathione removes skin cells. By activating and rejuvenating it, it has the effect of reducing the content of palmitoleic acid, thereby suppressing the production of the causative substance of the aging odor.
更に、グルタチオンはＳＨ基、アミノ基、及びカルボキシル基を有するため反応性に富み、産生された体臭の原因物質と反応してこれを高分子量化（グルタチオンと体臭の原因物質との付加反応物の分子量は、例えば３００以上であり、好ましくは３５０以上である。尚、分子量の上限は、例えば５００である）し、揮発性を著しく低下させることにより臭いの発生を抑制することができる。また、産生された体臭の原因物質にグルタチオンが付加すると極性が著しく高まるため、これによっても揮発性が低下する。 Furthermore, since glutathione has an SH group, an amino group, and a carboxyl group, it is highly reactive and reacts with the produced substance causing body odor to increase its molecular weight (the addition reaction product of glutathione and the substance causing body odor is reduced). The molecular weight is, for example, 300 or more, preferably 350 or more. The upper limit of the molecular weight is, for example, 500), and the generation of odor can be suppressed by remarkably reducing the volatility. In addition, when glutathione is added to the produced substance causing body odor, the polarity is significantly increased, so that the volatility is also reduced.
例えば体臭の原因物質が２−ノネナールである場合、グルタチオンは２−ノネナールと以下の様に反応して高分子量の付加反応物（下記式（ad-2）で表される化合物）が得られると考えられる。体臭の原因物質が２−ノネナール以外の不飽和アルデヒド（例えば、Ｃ4-10不飽和アルデヒド）の場合も、同様に反応すると考えられる。
本発明の体臭抑制剤は細胞毒性を有さず、安全性に優れる。そのため、例えば、外皮用薬やスキンケア用化粧料等に添加剤として使用することができる。 The body odor suppressant of the present invention has no cytotoxicity and is excellent in safety. Therefore, for example, it can be used as an additive to a medicine for skin or a cosmetic for skin care.
本発明の体臭抑制剤を外皮用薬やスキンケア用化粧料に添加する場合、その添加量は、式（１）で表される化合物、その塩、及びそれらの水和物から選択される少なくとも１種の濃度（２種以上含有する場合はその合計の濃度）が、例えば０．５〜７０μＭ程度となる範囲であり、好ましくは１０〜６０μＭ、特に好ましくは３０〜６０μＭ、最も好ましくは４０〜６０μＭである。 When the body odor suppressant of the present invention is added to a dermatological agent or a skin care cosmetic, the amount added is at least one selected from the compound represented by the formula (1), a salt thereof, and a hydrate thereof. The concentration of the species (when two or more species are contained, the total concentration) is, for example, in the range of about 0.5 to 70 μM, preferably 10 to 60 μM, particularly preferably 30 to 60 μM, and most preferably 40 to 60 μM. It is.
前記外皮用薬やスキンケア用化粧料の使用形態は、特に制限されず、例えば、ペースト状、ゲル状、液状、乳液状、クリーム状の製剤として使用することができる。また、シート状基材に含浸させてシート状製剤として使用したり、容器に封入してエアゾール状の製剤やスプレー状の製剤として使用することもできる。尚、外皮用薬やスキンケア用化粧料の使用回数は特に制限がなく、症状や用途に応じて適宜調整することができる。 The form of use of the skin medicine or skin care cosmetic is not particularly limited, and for example, it can be used as a paste, a gel, a liquid, an emulsion, or a cream. It can also be used as a sheet-form preparation by impregnating it in a sheet-form substrate, or enclosed in a container and used as an aerosol-form preparation or a spray-form preparation. In addition, the number of times of use of the medicine for skin and the cosmetic for skin care is not particularly limited, and can be appropriately adjusted according to symptoms and uses.
前記外皮用薬には、塗布剤（クリーム剤、軟膏剤、ゲル剤、ローション剤、液剤、チンキ剤）、貼付剤（パップ剤、プラスター剤、テープ剤、パッチ剤）が含まれる。 The dermatological agents include coating agents (creams, ointments, gels, lotions, solutions, tinctures) and patches (patches, plasters, tapes, patches).
前記スキンケア用化粧料には、例えば、化粧水、乳液等の基礎化粧料等が含まれる。 The cosmetics for skin care include, for example, basic cosmetics such as lotions and emulsions.
以下、実施例により本発明をより具体的に説明するが、本発明はこれらの実施例により限定されるものではない。 Hereinafter, the present invention will be described more specifically with reference to examples, but the present invention is not limited to these examples.
実施例１
式（II-2）で表される４種類の光学異性体（ジアステレオマー）の等量混合物（ＤＬ−２−アミノ−４−［（ＲＳｐ）−（３−カルボキシメチルフェノキシ）（メトキシ）ホスホリル］ブタン酸、抗菌性を有しない化合物、商品名「ＧＧｓＴｏｐ」、和光純薬工業（株）製）を体臭抑制剤（１）とした。
Example 1
Equivalent mixture (DL-2-amino-4-[(RSp)-(3-carboxymethylphenoxy) (methoxy) phosphoryl) of four kinds of optical isomers (diastereomers) represented by the formula (II-2) ] Butanoic acid, a compound having no antibacterial properties, trade name "GGsTop", manufactured by Wako Pure Chemical Industries, Ltd.) was used as body odor suppressant (1).
＜体臭抑制効果の評価＞
９名の男性パネラー（５３歳〜６２歳）が、朝晩、スプレーに詰めた体臭抑制剤（１）の０．００５％水溶液を、左腋下に各３回噴霧し、これを１か月続けた。その後、左腋下（体臭抑制剤処理区）と右腋下（体臭抑制剤未処理区）をそれぞれ別のカット綿（メタノールで２回洗浄し、その後１１０℃で二晩乾燥させて脱臭したもの）を使用して、皮膚表面をこすり取るように２０回擦って体表分泌物（サンプル）を採取した。
下記条件下でＳＰＭＥ法により抽出した臭い成分をガスクロマトグラフィーで分析した。
Head Space Solid Phase Micro Extraction (HS-SPME)GS-MS
SPME fiber:50/30 μm divinylbenzene / Carboxen on polydimethylsiloxane on a StableFlex fiber
Collection: 80℃ for 20 min
GS-MS
Column: DB-WAX
<Evaluation of body odor suppression effect>
Nine male panelists (53 to 62 years old) sprayed a 0.005% aqueous solution of body odor suppressant (1) in a spray onto the left armpit three times each in the morning and evening, and continued this for one month. Was. After that, the left axilla (body odor control agent-treated section) and the right axilla (body odor control agent-untreated section) were separately cut cotton (washed twice with methanol, then dried at 110 ° C. for 2 nights and deodorized). ), The body surface secretions (samples) were collected by rubbing the skin surface 20 times.
The odor components extracted by the SPME method under the following conditions were analyzed by gas chromatography.
Head Space Solid Phase Micro Extraction (HS-SPME) GS-MS
SPME fiber: 50/30 μm divinylbenzene / Carboxen on polydimethylsiloxane on a StableFlex fiber
Collection: 80 ℃ for 20 min
GS-MS
Column: DB-WAX
この結果、９名のうち４名のサンプルでは左腋下と右腋下において有意差が認められなかったが、５名のサンプルでは左腋下と右腋下において顕著な差が認められ、体臭抑制剤で処理された右腋下から採取したサンプルは、体臭抑制剤で処理を行っていない左腋下から採取したサンプルに比べて、２−ノネナールが還元されてなる２−ノネノール（保持時間：１３．４分）や、２−ノネナールの前駆体であるエチル−９−オクタデセノエート（保持時間：１６．０分）及びトリデカン（保持時間：１０．５分）の含有量が著しく低下しており、臭い成分の産生が抑制されたことが確認できた（図１、２参照）。 As a result, no significant difference was observed between the left axilla and the right axillary in four out of the nine samples, but a remarkable difference was observed between the left axilla and the right axilla in the five samples, and body odor was observed. The sample collected from the right axillary treated with the inhibitor was compared with a sample collected from the left axillary not treated with the body odor inhibitor, where 2-nonenal was obtained by reducing 2-nonenal (retention time: 13.4 minutes) and the content of ethyl-9-octadecenoate (retention time: 16.0 minutes) and tridecane (retention time: 10.5 minutes), which are precursors of 2-nonenal, are significantly reduced. It was confirmed that production of odorous components was suppressed (see FIGS. 1 and 2).
また、前記体臭抑制剤（１）は、下記方法によりグルタチオン合成促進効果を有することが確認できた。
すなわち、正常ヒト表皮細胞を、正常ヒト表皮角化細胞増殖用培地（商品名「HuMedia KG2」、倉敷紡績（株）製）を用いて９６穴マイクロプレートに、２．０×１０4cells/96wellの細胞密度にて播種した。播種２４時間後に、体臭抑制剤（１）２５μＭを含有した正常ヒト表皮角化細胞増殖用培地（商品名「HuMedia KB2」、倉敷紡績（株）製）と交換して培養を続けた。
３時間の培養後、１００μＭのフェニルメチルスルフォニルフルオライド含有リン酸バッファーを用い、超音波処理にて細胞を破砕し、グルタチオンレダクターゼリサイクリング法により総グルタチオン量を定量した。
この結果、３時間の培養後の総グルタチオン量は、培養前の１．１４倍に上昇していた。
In addition, it was confirmed that the body odor suppressant (1) had a glutathione synthesis promoting effect by the following method.
That is, 2.0 × 10 4 cells / 96 well of normal human epidermal cells were transferred to a 96-well microplate using a medium for normal human epidermal keratinocyte proliferation (trade name “HuMedia KG2”, manufactured by Kurashiki Boseki Co., Ltd.). At a cell density of Twenty-four hours after seeding, the medium was replaced with a culture medium for normal human epidermal keratinocyte growth (trade name “HuMedia KB2”, manufactured by Kurashiki Boseki Co., Ltd.) containing 25 μM of the body odor inhibitor (1), and the culture was continued.
After culturing for 3 hours, the cells were disrupted by sonication using a phosphate buffer containing 100 μM of phenylmethylsulfonyl fluoride, and the total amount of glutathione was quantified by a glutathione reductase recycling method.
As a result, the total amount of glutathione after culturing for 3 hours was increased to 1.14 times that before culturing.
更に、グルタチオンと、体臭の主な原因成分である２−ノネナールとの反応性を下記方法により評価した。
すなわち、反応容器にグルタチオン０．２ミリモル、２−ノネナール０．２ミリモル、水０．５ｍＬ、及びエタノール０．５ｍＬを仕込み、室温（２５℃）において１８時間反応させた。その後、反応液をＴＬＣ分析［展開溶媒（ヘキサン：酢酸エチル＝９：１），発色剤（５％リンモリブデン酸）］に付したところ、グルタチオンと２−ノネナールの付加反応物が生成し、２−ノネナールは消失したことが確認された。また、前記付加反応物（下記式（ad-2）で表される化合物）は分子量３７７．４１であり、揮発性が低く、臭いが著しく緩和された。
更に、２−ノネナールの使用量を０．２ミリモルから０．１ミリモルに変更した以外は上記方法と同様にしたところ、やはり２−ノネナールは消失したことが確認された。
Further, the reactivity between glutathione and 2-nonenal, which is a main cause component of body odor, was evaluated by the following method.
That is, 0.2 mmol of glutathione, 0.2 mmol of 2-nonenal, 0.5 mL of water, and 0.5 mL of ethanol were charged into a reaction vessel and reacted at room temperature (25 ° C.) for 18 hours. Thereafter, the reaction mixture was subjected to TLC analysis [developing solvent (hexane: ethyl acetate = 9: 1), color former (5% phosphomolybdic acid)], and an addition reaction product of glutathione and 2-nonenal was formed. -It was confirmed that nonenal had disappeared. The addition reaction product (compound represented by the following formula (ad-2)) had a molecular weight of 377.41 and low volatility, and the odor was remarkably reduced.
Furthermore, when the same method was used as described above except that the amount of 2-nonenal was changed from 0.2 mmol to 0.1 mmol, it was confirmed that 2-nonenal had disappeared.
これより、グルタチオンは体臭の主な原因成分である２−ノネナールと付加反応し、２−ノネナールを高分子量化して揮発性を低下させることにより、消臭効果を発揮することがわかった。
さらに、本発明の体臭抑制剤は、グルタチオンの合成促進効果を有することもわかった。
以上より、本発明の体臭抑制剤は、表皮細胞においてグルタチオンの合成を促進し、合成されたグルタチオンが体臭の原因物質と付加反応することによって消臭効果が発揮されると考えられる。
From this, it was found that glutathione exerts an deodorizing effect by causing an addition reaction with 2-nonenal, which is a main cause component of body odor, to increase the molecular weight of 2-nonenal to lower its volatility.
Furthermore, it was also found that the body odor suppressant of the present invention has a glutathione synthesis promoting effect.
From the above, it is considered that the body odor suppressant of the present invention promotes the synthesis of glutathione in epidermal cells, and the synthesized glutathione exerts an addition reaction with a substance causing body odor, thereby exhibiting a deodorizing effect.
Claims (1)
で表される化合物、その塩、及びそれらの水和物から選択される少なくとも１種を有効成分として含む、体臭抑制剤。 The following equation (1)
The body odor suppressant which contains at least 1 sort (s) selected from the compound represented by these, its salt, and those hydrates as an active ingredient.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP2018163456A JP7280562B2 (en) | 2018-08-31 | 2018-08-31 | Body odor suppressant |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP2018163456A JP7280562B2 (en) | 2018-08-31 | 2018-08-31 | Body odor suppressant |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JP2020033326A true JP2020033326A (en) | 2020-03-05 |
| JP7280562B2 JP7280562B2 (en) | 2023-05-24 |
Family
ID=69667085
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2018163456A Active JP7280562B2 (en) | 2018-08-31 | 2018-08-31 | Body odor suppressant |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JP7280562B2 (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2021250130A1 (en) * | 2020-06-10 | 2021-12-16 | Firmenich Sa | Prevention, reduction, or amelioration of old person smell |
Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH11286423A (en) * | 1998-03-31 | 1999-10-19 | Shiseido Co Ltd | Composition for suppressing body odor |
| WO2007066705A1 (en) * | 2005-12-07 | 2007-06-14 | Kyoto University | Phosphonic acid diester derivative and method for producing same |
| WO2007108438A1 (en) * | 2006-03-20 | 2007-09-27 | Rohto Pharmaceutical Co., Ltd. | External composition for promoting of glutathione production and relevant method |
| WO2010123102A1 (en) * | 2009-04-24 | 2010-10-28 | Yuasa Isao | Collagen production promoter, anti-photoaging agent, moisture-retention improvement agent, and composite for use on skin |
| JP2011168511A (en) * | 2010-02-17 | 2011-09-01 | Kyoto Univ | Renal insufficiency therapeutic agent |
| JP2017100993A (en) * | 2015-12-01 | 2017-06-08 | 株式会社ナールスコーポレーション | Glutathione production promoter |
-
2018
- 2018-08-31 JP JP2018163456A patent/JP7280562B2/en active Active
Patent Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH11286423A (en) * | 1998-03-31 | 1999-10-19 | Shiseido Co Ltd | Composition for suppressing body odor |
| WO2007066705A1 (en) * | 2005-12-07 | 2007-06-14 | Kyoto University | Phosphonic acid diester derivative and method for producing same |
| WO2007108438A1 (en) * | 2006-03-20 | 2007-09-27 | Rohto Pharmaceutical Co., Ltd. | External composition for promoting of glutathione production and relevant method |
| WO2010123102A1 (en) * | 2009-04-24 | 2010-10-28 | Yuasa Isao | Collagen production promoter, anti-photoaging agent, moisture-retention improvement agent, and composite for use on skin |
| JP2011168511A (en) * | 2010-02-17 | 2011-09-01 | Kyoto Univ | Renal insufficiency therapeutic agent |
| JP2017100993A (en) * | 2015-12-01 | 2017-06-08 | 株式会社ナールスコーポレーション | Glutathione production promoter |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2021250130A1 (en) * | 2020-06-10 | 2021-12-16 | Firmenich Sa | Prevention, reduction, or amelioration of old person smell |
Also Published As
| Publication number | Publication date |
|---|---|
| JP7280562B2 (en) | 2023-05-24 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| EP4081511B1 (en) | Carboxy derivatives with antiinflammatory properties | |
| Aursnes et al. | Stereoselective synthesis of protectin D1: a potent anti-inflammatory and proresolving lipid mediator | |
| JP2007137904A (en) | METHOD FOR PRODUCING SALT OR COMPLEX OF [R-(R*,R*)]-2-(4-FLUOROPHENYL)-beta,delta-DIHYDROXY-5-(1-METHYLETHYL)-3-PHENYL-4-[(PHENYLAMINO)CARBONYL]-1H-PYRROLE-1-HEPTANOIC ACID | |
| EP3235801B1 (en) | Carboxylic acid ester production method | |
| JP2022512736A (en) | Compounds containing deuterium | |
| EP3153495B1 (en) | Method for producing carboxylic acid anhydride, and method for producing carboxylic acid ester | |
| JP6778362B2 (en) | Glutathione production promoter | |
| JP2020033326A (en) | Deodorant | |
| JP2006052152A (en) | Antioxidative compound | |
| JP4070357B2 (en) | Skin preparation | |
| Li et al. | Stereoselective Synthesis of (−)‐Chloramphenicol,(+)‐Thiamphenicol and (+)‐Sphinganine via Chiral Tricyclic Iminolactone | |
| JP4329759B2 (en) | Novel shogaol compound and tyrosinase activity inhibitor by the compound | |
| JP2011068587A (en) | New aminoalcohol derivative salt, asymmetric organic molecule catalyst having aminoalcohol derivative salt structure and method for producing optically active compound with the asymmetric organic molecule catalyst | |
| Yamamoto et al. | Chemical synthesis of a very long-chain fatty acid, hexacosanoic acid (C26: 0), and the ceramide containing hexacosanoic acid | |
| JP2018203682A (en) | Involucrin gene expression promoter | |
| US20130005995A1 (en) | Method for preparing a fatty acid derivative | |
| EP0149201B1 (en) | Carboxylic acid derivatives, processes for their production and pharmaceutical preparations containing them | |
| SU618036A3 (en) | Method of obtaining amines or salts thereof | |
| Wadsworth et al. | A cyclic phosphate: base and metal acetate catalyzed ring opening | |
| JP3878095B2 (en) | Skin preparation for sunburn prevention | |
| JP7212900B2 (en) | Optically active 2-amino-phosphonoalkanoic acids, optically active 2-amino-phosphonoalkanoates, and hydrates thereof | |
| WO2018061884A1 (en) | Menthol derivative-containing composition | |
| WO2021162103A1 (en) | Compound and use thereof | |
| JP2017066070A (en) | Menthol derivative, method for producing the same and use therefor | |
| JP6826333B2 (en) | Narsgen optical resolution method |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20210716 |
|
| A977 | Report on retrieval |
Free format text: JAPANESE INTERMEDIATE CODE: A971007 Effective date: 20220311 |
|
| A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20220510 |
|
| A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20220629 |
|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20220908 |
|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A821 Effective date: 20220908 |
|
| A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20221221 |
|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20230202 |
|
| TRDD | Decision of grant or rejection written | ||
| A01 | Written decision to grant a patent or to grant a registration (utility model) |
Free format text: JAPANESE INTERMEDIATE CODE: A01 Effective date: 20230404 |
|
| A61 | First payment of annual fees (during grant procedure) |
Free format text: JAPANESE INTERMEDIATE CODE: A61 Effective date: 20230426 |
|
| R150 | Certificate of patent or registration of utility model |
Ref document number: 7280562 Country of ref document: JP Free format text: JAPANESE INTERMEDIATE CODE: R150 |