JPH045270A - Aminoalkane derivative - Google Patents
Aminoalkane derivativeInfo
- Publication number
- JPH045270A JPH045270A JP2106148A JP10614890A JPH045270A JP H045270 A JPH045270 A JP H045270A JP 2106148 A JP2106148 A JP 2106148A JP 10614890 A JP10614890 A JP 10614890A JP H045270 A JPH045270 A JP H045270A
- Authority
- JP
- Japan
- Prior art keywords
- group
- amino
- acid
- yield
- melting point
- 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
- 150000001875 compounds Chemical class 0.000 claims abstract description 30
- -1 sulfo, mesyl Chemical group 0.000 claims abstract description 20
- 125000006239 protecting group Chemical group 0.000 claims abstract description 11
- 150000003839 salts Chemical class 0.000 claims abstract description 8
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 7
- 125000003884 phenylalkyl group Chemical group 0.000 claims abstract description 7
- 125000003277 amino group Chemical group 0.000 claims abstract description 6
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 6
- 229910052736 halogen Chemical group 0.000 claims abstract description 5
- 150000002367 halogens Chemical group 0.000 claims abstract description 5
- 125000002768 hydroxyalkyl group Chemical group 0.000 claims abstract description 5
- 125000002088 tosyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1C([H])([H])[H])S(*)(=O)=O 0.000 claims abstract description 4
- 239000000126 substance Substances 0.000 claims abstract 2
- 229910052739 hydrogen Inorganic materials 0.000 claims description 10
- 125000000020 sulfo group Chemical group O=S(=O)([*])O[H] 0.000 claims description 5
- 239000001257 hydrogen Substances 0.000 claims description 4
- 125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 claims description 3
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 2
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 abstract description 15
- 239000002904 solvent Substances 0.000 abstract description 12
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 abstract description 9
- GEHJYWRUCIMESM-UHFFFAOYSA-L sodium sulfite Chemical compound [Na+].[Na+].[O-]S([O-])=O GEHJYWRUCIMESM-UHFFFAOYSA-L 0.000 abstract description 8
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 abstract description 4
- 239000002994 raw material Substances 0.000 abstract description 4
- 235000010265 sodium sulphite Nutrition 0.000 abstract description 4
- 238000003328 mesylation reaction Methods 0.000 abstract description 3
- KOUKXHPPRFNWPP-UHFFFAOYSA-N pyrazine-2,5-dicarboxylic acid;hydrate Chemical compound O.OC(=O)C1=CN=C(C(O)=O)C=N1 KOUKXHPPRFNWPP-UHFFFAOYSA-N 0.000 abstract description 3
- 238000007070 tosylation reaction Methods 0.000 abstract description 3
- HDECRAPHCDXMIJ-UHFFFAOYSA-N 2-methylbenzenesulfonyl chloride Chemical compound CC1=CC=CC=C1S(Cl)(=O)=O HDECRAPHCDXMIJ-UHFFFAOYSA-N 0.000 abstract description 2
- 229910000042 hydrogen bromide Inorganic materials 0.000 abstract description 2
- QARBMVPHQWIHKH-UHFFFAOYSA-N methanesulfonyl chloride Chemical compound CS(Cl)(=O)=O QARBMVPHQWIHKH-UHFFFAOYSA-N 0.000 abstract description 2
- 239000012359 Methanesulfonyl chloride Substances 0.000 abstract 1
- 239000000463 material Substances 0.000 abstract 1
- 238000002844 melting Methods 0.000 description 38
- 230000008018 melting Effects 0.000 description 38
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 21
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 18
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 17
- 238000000921 elemental analysis Methods 0.000 description 15
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 12
- 229910052757 nitrogen Inorganic materials 0.000 description 12
- 239000013078 crystal Substances 0.000 description 11
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 10
- 238000000354 decomposition reaction Methods 0.000 description 10
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 9
- 239000000243 solution Substances 0.000 description 9
- 239000002253 acid Substances 0.000 description 7
- 238000001914 filtration Methods 0.000 description 7
- 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 6
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 6
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 6
- 239000003456 ion exchange resin Substances 0.000 description 6
- 229920003303 ion-exchange polymer Polymers 0.000 description 6
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 6
- 238000000034 method Methods 0.000 description 6
- RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 6
- 238000006243 chemical reaction Methods 0.000 description 5
- 230000003287 optical effect Effects 0.000 description 5
- 239000011541 reaction mixture Substances 0.000 description 5
- LJGHYPLBDBRCRZ-UHFFFAOYSA-N 3-(3-aminophenyl)sulfonylaniline Chemical compound NC1=CC=CC(S(=O)(=O)C=2C=C(N)C=CC=2)=C1 LJGHYPLBDBRCRZ-UHFFFAOYSA-N 0.000 description 4
- 101150065749 Churc1 gene Proteins 0.000 description 4
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 4
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 4
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 4
- 229940024606 amino acid Drugs 0.000 description 4
- 235000001014 amino acid Nutrition 0.000 description 4
- 150000001413 amino acids Chemical class 0.000 description 4
- 229910052799 carbon Inorganic materials 0.000 description 4
- 125000004432 carbon atom Chemical group C* 0.000 description 4
- 239000003153 chemical reaction reagent Substances 0.000 description 4
- XEKOWRVHYACXOJ-UHFFFAOYSA-N ethyl acetate Substances CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 4
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 4
- KWGKDLIKAYFUFQ-UHFFFAOYSA-M lithium chloride Chemical compound [Li+].[Cl-] KWGKDLIKAYFUFQ-UHFFFAOYSA-M 0.000 description 4
- 238000004519 manufacturing process Methods 0.000 description 4
- 230000008635 plant growth Effects 0.000 description 4
- 230000001105 regulatory effect Effects 0.000 description 4
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical class O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 4
- 238000003756 stirring Methods 0.000 description 4
- 229910052717 sulfur Inorganic materials 0.000 description 4
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 3
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
- LSNNMFCWUKXFEE-UHFFFAOYSA-M Bisulfite Chemical compound OS([O-])=O LSNNMFCWUKXFEE-UHFFFAOYSA-M 0.000 description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- HEMHJVSKTPXQMS-DYCDLGHISA-M Sodium hydroxide-d Chemical compound [Na+].[2H][O-] HEMHJVSKTPXQMS-DYCDLGHISA-M 0.000 description 3
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
- 230000002378 acidificating effect Effects 0.000 description 3
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 3
- 235000019253 formic acid Nutrition 0.000 description 3
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 3
- 230000003647 oxidation Effects 0.000 description 3
- 238000007254 oxidation reaction Methods 0.000 description 3
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 3
- 238000006277 sulfonation reaction Methods 0.000 description 3
- OAZUHBHKEZYYSU-NUBCRITNSA-N (2S)-1-bromo-3-methylbutan-2-amine hydrochloride Chemical compound CC(C)[C@@H](CBr)N.Cl OAZUHBHKEZYYSU-NUBCRITNSA-N 0.000 description 2
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 2
- HVBSAKJJOYLTQU-UHFFFAOYSA-N 4-aminobenzenesulfonic acid Chemical compound NC1=CC=C(S(O)(=O)=O)C=C1 HVBSAKJJOYLTQU-UHFFFAOYSA-N 0.000 description 2
- PQUCIEFHOVEZAU-UHFFFAOYSA-N Diammonium sulfite Chemical compound [NH4+].[NH4+].[O-]S([O-])=O PQUCIEFHOVEZAU-UHFFFAOYSA-N 0.000 description 2
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 2
- AEMRFAOFKBGASW-UHFFFAOYSA-N Glycolic acid Chemical compound OCC(O)=O AEMRFAOFKBGASW-UHFFFAOYSA-N 0.000 description 2
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 2
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 2
- OFOBLEOULBTSOW-UHFFFAOYSA-N Malonic acid Chemical compound OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 2
- PXHVJJICTQNCMI-UHFFFAOYSA-N Nickel Chemical compound [Ni] PXHVJJICTQNCMI-UHFFFAOYSA-N 0.000 description 2
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- RWZYAGGXGHYGMB-UHFFFAOYSA-N anthranilic acid Chemical compound NC1=CC=CC=C1C(O)=O RWZYAGGXGHYGMB-UHFFFAOYSA-N 0.000 description 2
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 2
- 239000003054 catalyst Substances 0.000 description 2
- 238000010531 catalytic reduction reaction Methods 0.000 description 2
- 238000007796 conventional method Methods 0.000 description 2
- 238000001816 cooling Methods 0.000 description 2
- 238000010511 deprotection reaction Methods 0.000 description 2
- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 2
- FAMRKDQNMBBFBR-UHFFFAOYSA-N ethyl n-ethoxycarbonyliminocarbamate Chemical compound CCOC(=O)N=NC(=O)OCC FAMRKDQNMBBFBR-UHFFFAOYSA-N 0.000 description 2
- 239000000706 filtrate Substances 0.000 description 2
- 230000002140 halogenating effect Effects 0.000 description 2
- 230000026030 halogenation Effects 0.000 description 2
- 238000005658 halogenation reaction Methods 0.000 description 2
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 2
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 2
- AMXOYNBUYSYVKV-UHFFFAOYSA-M lithium bromide Chemical compound [Li+].[Br-] AMXOYNBUYSYVKV-UHFFFAOYSA-M 0.000 description 2
- 238000005259 measurement Methods 0.000 description 2
- UKVIEHSSVKSQBA-UHFFFAOYSA-N methane;palladium Chemical compound C.[Pd] UKVIEHSSVKSQBA-UHFFFAOYSA-N 0.000 description 2
- 239000012046 mixed solvent Substances 0.000 description 2
- 238000010647 peptide synthesis reaction Methods 0.000 description 2
- VLTRZXGMWDSKGL-UHFFFAOYSA-N perchloric acid Chemical compound OCl(=O)(=O)=O VLTRZXGMWDSKGL-UHFFFAOYSA-N 0.000 description 2
- WGYKZJWCGVVSQN-UHFFFAOYSA-N propylamine Chemical compound CCCN WGYKZJWCGVVSQN-UHFFFAOYSA-N 0.000 description 2
- 238000010898 silica gel chromatography Methods 0.000 description 2
- 229910052708 sodium Inorganic materials 0.000 description 2
- 239000011734 sodium Substances 0.000 description 2
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 2
- 235000017557 sodium bicarbonate Nutrition 0.000 description 2
- 239000007858 starting material Substances 0.000 description 2
- XOAAWQZATWQOTB-UHFFFAOYSA-N taurine Chemical compound NCCS(O)(=O)=O XOAAWQZATWQOTB-UHFFFAOYSA-N 0.000 description 2
- HJUGFYREWKUQJT-UHFFFAOYSA-N tetrabromomethane Chemical compound BrC(Br)(Br)Br HJUGFYREWKUQJT-UHFFFAOYSA-N 0.000 description 2
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 2
- ZMZDMBWJUHKJPS-UHFFFAOYSA-N thiocyanic acid Chemical compound SC#N ZMZDMBWJUHKJPS-UHFFFAOYSA-N 0.000 description 2
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 2
- MTCFGRXMJLQNBG-REOHCLBHSA-N (2S)-2-Amino-3-hydroxypropansäure Chemical compound OC[C@H](N)C(O)=O MTCFGRXMJLQNBG-REOHCLBHSA-N 0.000 description 1
- WVIVEABPZNXWQX-RXMQYKEDSA-N (2S)-2-amino-3-methylbutane-1-sulfonic acid Chemical compound N[C@H](CS(=O)(=O)O)C(C)C WVIVEABPZNXWQX-RXMQYKEDSA-N 0.000 description 1
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- SCOSYQFUYOGOAI-JTQLQIEISA-N (2s)-2-amino-3-phenylmethoxypropane-1-sulfonic acid Chemical compound OS(=O)(=O)C[C@@H](N)COCC1=CC=CC=C1 SCOSYQFUYOGOAI-JTQLQIEISA-N 0.000 description 1
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- KZSNJWFQEVHDMF-UHFFFAOYSA-N Valine Natural products CC(C)C(N)C(O)=O KZSNJWFQEVHDMF-UHFFFAOYSA-N 0.000 description 1
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 1
- FXOAPDMKKFVOGK-ZCFIWIBFSA-N [(2S)-2-amino-3-methylbutyl] methanesulfonate Chemical compound CC(C)[C@H](N)COS(C)(=O)=O FXOAPDMKKFVOGK-ZCFIWIBFSA-N 0.000 description 1
- 230000003213 activating effect Effects 0.000 description 1
- 235000004279 alanine Nutrition 0.000 description 1
- 229910052783 alkali metal Inorganic materials 0.000 description 1
- 150000001340 alkali metals Chemical class 0.000 description 1
- 229910052784 alkaline earth metal Inorganic materials 0.000 description 1
- 150000001342 alkaline earth metals Chemical class 0.000 description 1
- 125000004453 alkoxycarbonyl group Chemical group 0.000 description 1
- 229910052782 aluminium Inorganic materials 0.000 description 1
- XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 150000001412 amines Chemical class 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 239000012300 argon atmosphere Substances 0.000 description 1
- 239000012298 atmosphere Substances 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
- 239000002585 base Substances 0.000 description 1
- 235000010233 benzoic acid Nutrition 0.000 description 1
- 125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 description 1
- UCMIRNVEIXFBKS-UHFFFAOYSA-N beta-alanine Chemical compound NCCC(O)=O UCMIRNVEIXFBKS-UHFFFAOYSA-N 0.000 description 1
- 230000015572 biosynthetic process Effects 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
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 1
- 229910052794 bromium Inorganic materials 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
- 239000011575 calcium Substances 0.000 description 1
- 229910052791 calcium Inorganic materials 0.000 description 1
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 239000000460 chlorine Substances 0.000 description 1
- 229910052801 chlorine Inorganic materials 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- 235000013985 cinnamic acid Nutrition 0.000 description 1
- 229930016911 cinnamic acid Natural products 0.000 description 1
- 229910017052 cobalt Inorganic materials 0.000 description 1
- 239000010941 cobalt Substances 0.000 description 1
- GUTLYIVDDKVIGB-UHFFFAOYSA-N cobalt atom Chemical compound [Co] GUTLYIVDDKVIGB-UHFFFAOYSA-N 0.000 description 1
- 229910052802 copper Inorganic materials 0.000 description 1
- 239000010949 copper Substances 0.000 description 1
- 239000002537 cosmetic Substances 0.000 description 1
- 239000012043 crude product Substances 0.000 description 1
- 239000002178 crystalline material Substances 0.000 description 1
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
- FAMRKDQNMBBFBR-BQYQJAHWSA-N diethyl azodicarboxylate Substances CCOC(=O)\N=N\C(=O)OCC FAMRKDQNMBBFBR-BQYQJAHWSA-N 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- IDGUHHHQCWSQLU-UHFFFAOYSA-N ethanol;hydrate Chemical compound O.CCO IDGUHHHQCWSQLU-UHFFFAOYSA-N 0.000 description 1
- 125000002485 formyl group Chemical group [H]C(*)=O 0.000 description 1
- 239000001530 fumaric acid Substances 0.000 description 1
- 239000000174 gluconic acid Substances 0.000 description 1
- 235000012208 gluconic acid Nutrition 0.000 description 1
- 150000002431 hydrogen Chemical group 0.000 description 1
- 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 description 1
- 229910052740 iodine Inorganic materials 0.000 description 1
- 239000011630 iodine Substances 0.000 description 1
- 229910052742 iron Inorganic materials 0.000 description 1
- 229960000310 isoleucine Drugs 0.000 description 1
- AGPKZVBTJJNPAG-UHFFFAOYSA-N isoleucine Natural products CCC(C)C(N)C(O)=O AGPKZVBTJJNPAG-UHFFFAOYSA-N 0.000 description 1
- PHTQWCKDNZKARW-UHFFFAOYSA-N isopentyl alcohol Natural products CC(C)CCO PHTQWCKDNZKARW-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
- 239000010410 layer Substances 0.000 description 1
- 238000001819 mass spectrum Methods 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- 150000002739 metals Chemical class 0.000 description 1
- DWKPPFQULDPWHX-UHFFFAOYSA-N methyl 2-aminopropanoate Chemical compound COC(=O)C(C)N DWKPPFQULDPWHX-UHFFFAOYSA-N 0.000 description 1
- WBYWAXJHAXSJNI-UHFFFAOYSA-N methyl p-hydroxycinnamate Natural products OC(=O)C=CC1=CC=CC=C1 WBYWAXJHAXSJNI-UHFFFAOYSA-N 0.000 description 1
- 235000013336 milk Nutrition 0.000 description 1
- 239000008267 milk Substances 0.000 description 1
- 210000004080 milk Anatomy 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- PSZYNBSKGUBXEH-UHFFFAOYSA-N naphthalene-1-sulfonic acid Chemical compound C1=CC=C2C(S(=O)(=O)O)=CC=CC2=C1 PSZYNBSKGUBXEH-UHFFFAOYSA-N 0.000 description 1
- 229910052759 nickel Inorganic materials 0.000 description 1
- 229910017604 nitric acid Inorganic materials 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 239000012044 organic layer Substances 0.000 description 1
- 150000002978 peroxides Chemical class 0.000 description 1
- 239000003208 petroleum Substances 0.000 description 1
- COLNVLDHVKWLRT-UHFFFAOYSA-N phenylalanine Natural products OC(=O)C(N)CC1=CC=CC=C1 COLNVLDHVKWLRT-UHFFFAOYSA-N 0.000 description 1
- 125000000612 phthaloyl group Chemical group C(C=1C(C(=O)*)=CC=CC1)(=O)* 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 229960003975 potassium Drugs 0.000 description 1
- 229910000028 potassium bicarbonate Inorganic materials 0.000 description 1
- 235000015497 potassium bicarbonate Nutrition 0.000 description 1
- 239000011736 potassium bicarbonate Substances 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
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
- 108090000765 processed proteins & peptides Proteins 0.000 description 1
- 235000019260 propionic acid Nutrition 0.000 description 1
- ODLMAHJVESYWTB-UHFFFAOYSA-N propylbenzene Chemical compound CCCC1=CC=CC=C1 ODLMAHJVESYWTB-UHFFFAOYSA-N 0.000 description 1
- IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 description 1
- 230000006340 racemization Effects 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- UQDJGEHQDNVPGU-UHFFFAOYSA-N serine phosphoethanolamine Chemical compound [NH3+]CCOP([O-])(=O)OCC([NH3+])C([O-])=O UQDJGEHQDNVPGU-UHFFFAOYSA-N 0.000 description 1
- 239000012279 sodium borohydride Substances 0.000 description 1
- 229910000033 sodium borohydride Inorganic materials 0.000 description 1
- 229910052938 sodium sulfate Inorganic materials 0.000 description 1
- 235000011152 sodium sulphate Nutrition 0.000 description 1
- 125000001424 substituent group Chemical group 0.000 description 1
- 229950000244 sulfanilic acid Drugs 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- 229960003080 taurine Drugs 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
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 1
- 125000002221 trityl group Chemical group [H]C1=C([H])C([H])=C([H])C([H])=C1C([*])(C1=C(C(=C(C(=C1[H])[H])[H])[H])[H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 1
- OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 description 1
- 239000004474 valine Substances 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- 229910052725 zinc Inorganic materials 0.000 description 1
- 239000011701 zinc Substances 0.000 description 1
Classifications
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P20/00—Technologies relating to chemical industry
- Y02P20/50—Improvements relating to the production of bulk chemicals
- Y02P20/55—Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups
Abstract
Description
【発明の詳細な説明】
（産業上の利用分野）
本発明は新規アミノアルカン誘導体及びその薬学的に許
容される塩に関する。DETAILED DESCRIPTION OF THE INVENTION (Industrial Application Field) The present invention relates to novel aminoalkane derivatives and pharmaceutically acceptable salts thereof.
（従来の技術）
アミノ酸のカルボキシル基にあたる部分がスルホ基であ
るタウリン等のアミノｆｌ１Ｍ縁体は、医薬、化粧品な
ど種々の用途に有用な化合物として知られている。本発
明者らは、これらアミノ酸類縁体に関して研究を行った
結果、植物生長調整作用を有する新規アミノアルカン誘
導体並びに該化合物を製造する際に合成中間体として有
用な新規化合物を見出し、本発明を完成した。(Prior Art) Amino fl1M derivatives such as taurine, in which the portion corresponding to the carboxyl group of the amino acid is a sulfo group, are known as compounds useful for various uses such as medicine and cosmetics. As a result of conducting research on these amino acid analogs, the present inventors discovered a novel aminoalkane derivative having a plant growth regulating effect and a new compound useful as a synthetic intermediate in the production of the compound, and completed the present invention. did.
（発明が解決しようとする問題点）
本発明の目的は、植物生長調整作用を有する新規アミノ
アルカン誘導体及びその合成中間体を提供することにあ
る。(Problems to be Solved by the Invention) An object of the present invention is to provide a novel aminoalkane derivative having a plant growth regulating effect and a synthetic intermediate thereof.
（問題点を解決するための手段）
本発明化合物は、下記一般式（１）で表される新規アミ
ノアルカン誘導体である。(Means for solving the problems) The compound of the present invention is a novel aminoalkane derivative represented by the following general formula (1).
■
〔式中、Ｒは水素又はアミノ基の保護基、Ｙは低級アル
キル基、フェニル基、フェニルアルキル基、ヒドロキシ
アルキル基、ヒドロキシフェニルアルキル基又はフェニ
ルアルキルオキシアルキル基、Ｘはスルホ基、メシル基
、トシル基、アセチルチオ基又はハロゲンを表す。〕
上記一般式（１）において、只の表すアミノ基の保護基
としては、ペプチド合成化学の分野で用いられている通
常の保護基が利用でき、即ち、ｔ−ブトキシカルボニル
、【−ペントキシカルボニル基等の低級アルコキシカル
ボニル基、ヘンシルオキシカルボニル基、ｏ−クロロベ
ンジルオキシカルボニル、ｐ−ニトロヘンシルオキシカ
ルボニル、ｐ−メトキシベンジルオキシカルボニル基等
の置換基を有するベンジルオキシカルボニル基、トシル
基、トリチル基、ホルミル基、フタロイル基、０−ニト
ロフェニルスルフェニル基、９−フルオレニルメチルオ
キシカルボニル基などが挙げられる。[In the formula, R is hydrogen or a protecting group for an amino group, Y is a lower alkyl group, phenyl group, phenylalkyl group, hydroxyalkyl group, hydroxyphenylalkyl group, or phenylalkyloxyalkyl group, X is a sulfo group, mesyl group , represents a tosyl group, an acetylthio group, or a halogen. ] In the above general formula (1), as a protecting group for the amino group simply represented, a common protecting group used in the field of peptide synthetic chemistry can be used, such as t-butoxycarbonyl, [-pentoxycarbonyl] benzyloxycarbonyl group having a substituent such as lower alkoxycarbonyl group, hensyloxycarbonyl group, o-chlorobenzyloxycarbonyl, p-nitrohensyloxycarbonyl, p-methoxybenzyloxycarbonyl group, tosyl group, Examples include trityl group, formyl group, phthaloyl group, 0-nitrophenylsulfenyl group, and 9-fluorenylmethyloxycarbonyl group.
Ｙは水素、低級アルキル基、好ましくはメチル、エチル
、プロピル、イソプロピル、ブチル、イソフチル、５ｅ
ｃ−ブチル、ｔｅｒｔ−ブチル基等の直鎖又は分校状の
炭素数１乃至４のアルキル基、フェニル基、フェニルア
ルキル基、好ましくはメチル、エチル、プロピル基等の
炭素数１乃至３のアルキル基にフェニル基が結合したフ
ェニルアルキル基、ヒドロキシアルキル基、好ましくは
ヒドロキシメチル、ヒドロキシエチル、ヒドロキシプロ
ピル基等の炭素数１乃至３のヒドロキシアルキル基、ヒ
ドロキシフェニルアルキル基、好ましくは前述のフェニ
ルアルキル基に水酸基が結合したヒドロキシフェニルア
ルキル基、或いはフェニルアルキルオキシアルキル基、
好ましくはメチル、エチル、プロピル基等の炭素数１乃
至３のアルキル基にフェニル基が結合したフェニルアル
キル基を有するフェニルアルキルオキシメチル、フェニ
ルアルキルオキシエチル、フェニルアルキルオキシプロ
ピル
Ｘはスルホ基、メシル基、トンル基、アセチフレチオ基
又は塩素、臭素、沃素等のノ＼ロゲンを表す。Y is hydrogen, a lower alkyl group, preferably methyl, ethyl, propyl, isopropyl, butyl, isophthyl, 5e
Straight chain or branched alkyl groups having 1 to 4 carbon atoms such as c-butyl and tert-butyl groups, phenyl groups, phenylalkyl groups, preferably alkyl groups having 1 to 3 carbon atoms such as methyl, ethyl, and propyl groups. A phenylalkyl group to which a phenyl group is bonded, a hydroxyalkyl group, preferably a hydroxyalkyl group having 1 to 3 carbon atoms such as hydroxymethyl, hydroxyethyl, hydroxypropyl group, hydroxyphenylalkyl group, preferably the above-mentioned phenylalkyl group. A hydroxyphenylalkyl group to which a hydroxyl group is bonded, or a phenylalkyloxyalkyl group,
Preferably, phenylalkyloxymethyl, phenylalkyloxyethyl, and phenylalkyloxypropyl X having a phenylalkyl group in which a phenyl group is bonded to an alkyl group having 1 to 3 carbon atoms such as methyl, ethyl, and propyl group are sulfo group and mesyl group. , represents a tonl group, an acetifletio group, or a halogen such as chlorine, bromine, or iodine.
本発明アミノアルカン誘導体はその薬学的に許容される
塩を包含し、例えば、塩酸、硫酸、硝酸、臭化水素酸、
リン酸、過塩素酸、チオシアン酸、ホウ酸等の無機酸、
ギ酸、酢酸、Ａ口酢酸、プロピオン酸、グリコール酸、
クエン酸、酒石酸、コノ＼り酸、グルコン酸、乳Ｍ、マ
ロン酸、フマール酸、アントラニル酸、安息香酸、ケイ
皮酸、ｐ−トルエンスルホン酸、ナフタレンスルホン酸
、スルファニル酸等の有機酸との酸付加塩、或いはナト
リウム、カリウム等のアルカリ金属、カルシウム、バリ
ウム等のアルカリ土類金属、その他のアルミニウム等の
金属との塩、又はアンモニウム、有機アミンとの塩など
が挙げられる。The aminoalkane derivatives of the present invention include pharmaceutically acceptable salts thereof, such as hydrochloric acid, sulfuric acid, nitric acid, hydrobromic acid,
Inorganic acids such as phosphoric acid, perchloric acid, thiocyanic acid, boric acid,
Formic acid, acetic acid, A-acetic acid, propionic acid, glycolic acid,
With organic acids such as citric acid, tartaric acid, conoric acid, gluconic acid, milk M, malonic acid, fumaric acid, anthranilic acid, benzoic acid, cinnamic acid, p-toluenesulfonic acid, naphthalenesulfonic acid, and sulfanilic acid. Examples include acid addition salts, salts with alkali metals such as sodium and potassium, alkaline earth metals such as calcium and barium, other metals such as aluminum, and salts with ammonium and organic amines.
又、本発明化合物はその金属錯化合物を包含し、例えば
亜鉛、ニッケル、コバルト、銅、鉄等との錯化合物が挙
げられる。Further, the compound of the present invention includes its metal complex compounds, such as complex compounds with zinc, nickel, cobalt, copper, iron, etc.
これらの塩並びに金属錯化合物は公知の方法により遊離
の本発明アミノアルカン誘導体より製造でき、或いは相
互に変換することができる。These salts and metal complex compounds can be produced from the free aminoalkane derivative of the present invention by known methods, or can be converted into each other.
本発明化合物において光学異性体が存在する場合には、
本発明はそのいずれをも包含する。When optical isomers exist in the compound of the present invention,
The present invention includes both of them.
次に、本発明化合物の製造方法の一例を述べる。Next, an example of a method for producing the compound of the present invention will be described.
（１）原料物質として、前記一般式（１）中のＸが水酸
基である化合物を用いる。該原料物質は、試薬として入
手可能なものも多く、又、アラニン、バリン、ロイシン
、イソロイシン、フェニルアラニン、チロシン、セリン
等のアミノ酸を通常の方法により還元して得ることもで
きる。これらアミノ酸類はＤ体、Ｌ体の分割された光学
異性体が多く製造されており、本発明化合物の各々の異
性体を得る際には便利である。(1) A compound in which X in the general formula (1) is a hydroxyl group is used as a raw material. Many of these raw materials are available as reagents, and they can also be obtained by reducing amino acids such as alanine, valine, leucine, isoleucine, phenylalanine, tyrosine, and serine using conventional methods. Many of these amino acids are produced as optical isomers divided into D-form and L-form, which is convenient for obtaining each isomer of the compound of the present invention.
まず、出発物質アミノアルコール化合物のメシル化、ト
シル化、ハロゲン化、チオエート化を行う。First, the starting amino alcohol compound is mesylated, tosylated, halogenated, and thioated.
例えば、塩化メチレン等の反応を阻害しない適当な溶媒
中、トリエチルアミン等の塩基の存在下、塩化メタンス
ルホン酸を反応させることによりメシル化反応を行うこ
とができ、又、塩化トルエンスルホン酸等の試薬を用い
ることにより、トシル化することができる。For example, the mesylation reaction can be carried out by reacting methanesulfonic acid chloride in the presence of a base such as triethylamine in a suitable solvent that does not inhibit the reaction such as methylene chloride, or by reacting a reagent such as toluenesulfonic acid chloride. Tosylation can be achieved by using
ハロゲン化法としては、テトラブロモメタンとトリフェ
ニルホスフィンを反応させる方法や臭化水素等でハロゲ
ン化する方法などが挙げられ、又、メシル化した化合物
を臭化リチウム等の試薬によりハロゲン化する方法も利
用できる。又、トリフェニルホスフィン及びジエチルア
ゾカルボキシレート等の反応試剤で原料物質の水酸基を
活性化した後、チオ酢酸と反応させることによりチオエ
ート化することができる。Examples of halogenation methods include a method of reacting tetrabromomethane with triphenylphosphine, a method of halogenating with hydrogen bromide, etc., and a method of halogenating a mesylated compound with a reagent such as lithium bromide. Also available. Further, after activating the hydroxyl group of the raw material with a reaction reagent such as triphenylphosphine and diethylazocarboxylate, it can be converted into a thioate by reacting it with thioacetic acid.
これらのメシル化、トシル化、ハロゲン化、チオエート
化に際しては、出発物質の反応に関与しないアミノ基及
び水酸基を通常のペプチド合成等で用いられる保護基に
より保護しておくのが好ましいが、反応の種類に応じて
保護する必要のない場合もある。During these mesylation, tosylation, halogenation, and thioate formation, it is preferable to protect the amino groups and hydroxyl groups of the starting materials that do not participate in the reaction with protective groups used in ordinary peptide synthesis, etc.; Depending on the type, protection may not be necessary.
（２）次に、上記（１）で得られたアミノアルカン化合
物のメシルオキシ、トシルオキシ、ハロゲン、チオエー
ト誘導体のスルホン化を行う。(2) Next, the mesyloxy, tosyloxy, halogen, and thioate derivatives of the aminoalkane compound obtained in the above (1) are sulfonated.
スルホン化反応の前に、ｔ−ブトキシカルボニル等でア
ミノ基を保護されている化合物に関しては、該保護基を
除去しておくのが好ましい。保護基の種類によってそれ
ぞれ好ましい脱保護基反応が適用できるが、ペプチド合
成化学で用いられる接触還元、酸分解等の通常の方法に
より行うことができる。For compounds whose amino groups are protected with t-butoxycarbonyl or the like, it is preferable to remove the protecting group before the sulfonation reaction. Depending on the type of protecting group, a preferable deprotection reaction can be applied, but it can be carried out by conventional methods such as catalytic reduction and acid decomposition used in peptide synthesis chemistry.
スルホン化反応は、水等の反応を阻害しない適当な溶媒
中、亜硫酸ナトリウム、亜硫酸アンモニウム等と室温で
数時間乃至数十時間反応させることにより実施でき、一
般式（１）中のＸがスルホ基である本発明化合物を得る
ことができる。The sulfonation reaction can be carried out by reacting with sodium sulfite, ammonium sulfite, etc. at room temperature for several hours to several tens of hours in a suitable solvent such as water that does not inhibit the reaction. The compound of the present invention can be obtained.
チオエート誘導体に関しては、過蟻酸酸化によりスルホ
ン化することができる。保護基としてｔ−ブトキシカル
ボニル等を用いた場合、過蟻酸酸化と同時に脱保護基反
応を行うことができ、又、ヘンシルオキシカルボニル等
の保護基の場合には、過蟻酸酸化後に過剰の過酸化物を
パラジウム−炭素等で還元する反応時に保護基を除去す
ることができ、操作が簡便で好ましい。For thioate derivatives, sulfonation can be achieved by performic acid oxidation. When t-butoxycarbonyl or the like is used as a protecting group, deprotection reaction can be carried out simultaneously with performic acid oxidation, and when using a protecting group such as hensyloxycarbonyl, excess perforate can be removed after performic acid oxidation. The protecting group can be removed during the reaction of reducing the oxide with palladium-carbon or the like, and the operation is simple and preferable.
上述した本発明化合物の製造方法に従えば、分割された
光学異性体を出発物質として使用することにより、ラセ
ミ化することなく最終のアミノアルカンスルホン酸誘導
体の光学異性体を各々製造することができる。According to the method for producing the compound of the present invention described above, each of the final optical isomers of the aminoalkanesulfonic acid derivative can be produced without racemization by using the resolved optical isomers as starting materials. .
得られた本発明化合物は、クロマトグラフィー、再結晶
等の通常の手段により精製し、元素分析、融点、Ｉ Ｒ
，ＮＭＲ，ＵＶ、マススペクトル等により同定を行った
。尚、比旋光度はナトリウムのＤＩＲを用いて測定した
。The obtained compound of the present invention was purified by conventional means such as chromatography and recrystallization, and subjected to elemental analysis, melting point, I.R.
, NMR, UV, mass spectrum, etc. were used for identification. Note that the specific optical rotation was measured using sodium DIR.
以下に、本発明製造方法の実施例を示す。Examples of the manufacturing method of the present invention are shown below.
（実施例）
実施例１゜
（１１１８，９ｇの（Ｓ）−２−（Ｎ−ブトキシカルボ
ニル）アミノプロピオン酸と２０ｇの炭酸水素カリウム
をジメチルホルムアミドに溶かし、１０−のヨウ化メチ
ルを室温で加えた。２０時間かき混ぜた後、水３００−
に反応混合物を加え、ヘンゼンー酢酸エチルの混合溶媒
で抽出した。抽出液を水、５％炭酸水素ナトリウム水溶
液、１０％クエン酸水溶液、飽和食塩水で順次洗浄した
後、無水硫酸ナトリウム上で乾燥した。溶媒を減圧下に
溜去して、（Ｓ） −２−（Ｎ−ｔ−ブトキシカルボニ
ル）アミノプロピオン酸メチルエステルを油状物として
得た。(Example) Example 1゜(1118.9 g of (S)-2-(N-butoxycarbonyl)aminopropionic acid and 20 g of potassium hydrogen carbonate were dissolved in dimethylformamide, and 10-methyl iodide was added at room temperature. After stirring for 20 hours, water 300-
The reaction mixture was added to the solution and extracted with a mixed solvent of Hensen-ethyl acetate. The extract was washed successively with water, a 5% aqueous sodium bicarbonate solution, a 10% aqueous citric acid solution, and saturated brine, and then dried over anhydrous sodium sulfate. The solvent was distilled off under reduced pressure to obtain (S)-2-(Nt-butoxycarbonyl)aminopropionic acid methyl ester as an oil.
（２） （Ｓ）−２−（Ｎ−ｔ−ブトキシカルボニル）
アミノプロピオン酸メチルエステルと８．４８ｇの塩化
リチウムをテトラヒドロフラン１４０−に溶かし、７．
５７ｇの水素化ホウ素ナトリウムを加えた。室温でさら
に２８０−のエタノールを加え２０時間かき混ぜた０反
応混合物に１０％クエン酸水溶液を加えて約ｐＨ４とし
た後、有Ｉ！溶媒を減圧下に溜去した。残渣水層を塩化
メチレンで抽出処理を行い、水、１０％クエン酸水溶液
、飽和食塩水で順次洗浄し、無水硫酸ナトリウム上で乾
燥した。溶媒を減圧下に溜去し、析出した白色結晶をエ
ーテル、石油エーテルから濾取して、１６．３ｇの（Ｓ
） −２−（Ｎ−ｔ−ブトキシカルボニル）アミノプロ
パンｌ−オールを得た。(2) (S)-2-(N-t-butoxycarbonyl)
7. Dissolve aminopropionic acid methyl ester and 8.48 g of lithium chloride in tetrahydrofuran 140-.
57g of sodium borohydride was added. After adding 10% citric acid aqueous solution to the reaction mixture, which was stirred for 20 hours by adding 280 ml of ethanol at room temperature, the pH was adjusted to about 4, and then the pH was adjusted to about 4. The solvent was distilled off under reduced pressure. The residual aqueous layer was extracted with methylene chloride, washed successively with water, a 10% aqueous citric acid solution, and saturated brine, and dried over anhydrous sodium sulfate. The solvent was distilled off under reduced pressure, and the precipitated white crystals were filtered from ether and petroleum ether to give 16.3 g of (S
) -2-(N-t-butoxycarbonyl)aminopropane l-ol was obtained.
収率：９３％
融点： ５６−５７°Ｃ
Ｃａ”Ｊ ”−１０，５（ｃ＝１． ＣＨＣｈ）（１）
及び（２）の方法と同様にして、以下の化合物を得た。Yield: 93% Melting point: 56-57°C Ca”J”-10,5 (c=1.CHCh) (1)
The following compounds were obtained in the same manner as in method (2).
（Ｒ） −２−（Ｎ−ｔ−ブトキシカルボニル）アミノ
プロパン１−オールを得た。(R)-2-(N-t-butoxycarbonyl)aminopropane-1-ol was obtained.
収 率：９５％
融点： ６０−６１℃
（Ｃ１） ” ＝ ＋ １０．６ （ｃ＝１． ＣＨＣ
Ｉｚ）（Ｓ） −２−（Ｎ−ｔ−ブトキシカルボニル）
アミノ−３−メチルブタン−１−オール
（Ｒ）−２−（Ｎ−ｔ−ブトキシカルボニル）アミノ−
３−メチルブタン−１−オール
（Ｓ）−２−（Ｎ−ｔ−ブトキシカルボニル）アミノ−
４−メチルペンタン−１−オール
（Ｓ）−２−（Ｎ−ｔ−ブトキシカルボニル）アミノ−
３−フェニルプロパン−１−オール
（Ｒ） −２−（Ｎ−ｔ−ブトキシカルボニル）アミノ
−３−フェニルプロパン−１−オール
（Ｒ） −２−（Ｎ−ｔ−ブトキシカルボニル）アミノ
−２−フェニルエタノール
（Ｓ）−３−ベンジルオキシ−２−（Ｎ−ｔ−ブトキシ
カルボニル）アミノプロパン−ｌ−オール
（３）１４．９ｇの（Ｓ） −２−（Ｎ−ｔ−ブトキシ
カルボニル）アミノプロパン−１−オールと９．１１ｇ
のトリエチルアミンを３００−の塩化メチレンに溶がし
、−５℃にて９０ｍ＊ｏ ｌの塩化メタンスルホン酸の
塩化メチレン溶液を徐々に滴下して加えた。溶媒を減圧
下に溜去した後、残渣を酢酸エチルと水に溶かした。有
機層を分離して水と飽和食塩水で洗浄した後、無水硫酸
ナトリウム上で乾燥し、溶媒を減圧下に溜去して２０．
６ｇの（Ｓ）２− （Ｎ−ｔ−ブトキシカルボニル）ア
ミノ−１−（メタンスルホニル）オキシプロパンを得た
。Yield: 95% Melting point: 60-61℃ (C1) ” = + 10.6 (c = 1.CHC
Iz)(S) -2-(N-t-butoxycarbonyl)
Amino-3-methylbutan-1-ol (R)-2-(N-t-butoxycarbonyl)amino-
3-Methylbutan-1-ol (S)-2-(N-t-butoxycarbonyl)amino-
4-Methylpentan-1-ol (S)-2-(N-t-butoxycarbonyl)amino-
3-phenylpropan-1-ol (R) -2-(N-t-butoxycarbonyl)amino-3-phenylpropan-1-ol (R) -2-(N-t-butoxycarbonyl)amino-2- Phenylethanol (S)-3-benzyloxy-2-(N-t-butoxycarbonyl)aminopropan-l-ol (3) 14.9 g of (S)-2-(N-t-butoxycarbonyl)aminopropane -1-ol and 9.11g
of triethylamine was dissolved in 300 methylene chloride, and a solution of 90 m*ol of chlorinated methanesulfonic acid in methylene chloride was gradually added dropwise at -5°C. After distilling off the solvent under reduced pressure, the residue was dissolved in ethyl acetate and water. The organic layer was separated, washed with water and saturated brine, dried over anhydrous sodium sulfate, and the solvent was distilled off under reduced pressure to give 20.
6 g of (S)2-(Nt-butoxycarbonyl)amino-1-(methanesulfonyl)oxypropane was obtained.
収率：９６％
融点： ７５−７６°Ｃ
（α） ！４＝ ３０．２ （ｃ＝１． ＣＨＣｈ）
ＮＭ Ｒ（ＤＭＳＯ−ｄｉ） ’ １．０６（３Ｈ，
ｄ、Ｊ＝７Ｈｚ）、 １．３９（９Ｈ，ｓ）、 ３．１
６（３Ｈ，ｓ）、 ３．６９−３．８０（１Ｂ、＋ｗ）
、 ４．０４（２Ｈ，ｄ、Ｊ＝６Ｈｚ）、 ６．９３（
ＩＨ，ｄ、Ｊ＝８Ｈｚ）同様にして、以下の化合物を得
た。Yield: 96% Melting point: 75-76°C (α)! 4=30.2 (c=1.CHCh)
NMR(DMSO-di)' 1.06 (3H,
d, J=7Hz), 1.39 (9H, s), 3.1
6 (3H, s), 3.69-3.80 (1B, +w)
, 4.04 (2H, d, J=6Hz), 6.93 (
IH, d, J=8Hz) The following compounds were obtained in the same manner.
（Ｒ）−２４Ｎ−ｔ−ブトキシカルボニル）アミノ−１
−（メタンスルホニル）オキシプロパン
収率：９８％
融 点： ７５−７６°Ｃ（分解）
（αｌｌ ”＝ ＋２９．９ （Ｃ＝Ｌ ＣＨＣｌ３
）（Ｓ） −２−（Ｎ−ｔ−ブトキシカルボニル）アミ
ノ−１−（メタンスルホニル）オキシ−３−メチルブタ
ン収率：８９％
融 点： ７５−７７°Ｃ（分解）
〔α） ”＝ ３４．９ （ｃ＝ｌ、 ＣＨＣｈ）Ｎ
ＭＲ（ＤＭＳＯ−ｄＪ ： ０．８４（３Ｈ，ｄ、Ｊ
＝７Ｈｚ）、 ０．８７（３Ｈ，ｄ、Ｊ＝７Ｈｚ）、
１．３９（９Ｈ，ｓ）、 １．７５（ＩＨ，ｄｑｑ、Ｊ
＝７゜７、７Ｈｚ）、 ３．１６（３Ｈ，ｓ）、 ３．
５０（ＩＯ，ｄｄｄｄ、Ｊ＝４．７７、９Ｈｚ）、 ４
．０７（ＩＨ，ｄｄ、Ｊ＝７．１０Ｈｚ）、 ４．１８
（１８゜ｄｄ、Ｊ＝４．１９Ｈｚ）、 ６．９１（１８
，ｄ、Ｊ＝９Ｈｚ）（Ｒ） −２−（Ｎ−ｔ−ブトキシ
カルボニル）アミノ−１−（メタンスルホニル）オキシ
−３−メチルブタン収率：９０％
融 点： ７３−７５°Ｃ（分解）
〔α） ”＝ ＋３３．０ （ｃ＝Ｌ ＣＨＣｌ３）（
Ｓ） −２−（Ｎ−ｔ−ブトキシカルボニル）アミノ−
１−（メタンスルホニル）オキシ−４−メチルペンタン
収率：９７％
融点： ８２−８３℃
〔α） ”＝ ３２．７ （ｃ＝１． ＣＨＣｈ）（
Ｓ） −２−（Ｎ−ｔ−ブトキシカルボニル）アミノ−
１−（メタンスルホニル）オキシ−３−フェニルプロパ
ン収率：９３％
融 点： １１６−１１７°Ｃ（分解）Ｃα、１ ”
＝ １７．４ （Ｃ＝Ｌ Ｃ）ＨＣｌ３）ＮＭＲ（Ｄ
ＭＳＯ−ｄ６） ： １．３１（９Ｈ，ｓ）、 ２．
６７（ＩＨ，ｄｄＪ＝９ １４Ｈｚ）、 ２．７９（Ｌ
Ｈ，ｄｄ、Ｊ＝５．１４ｆｌｚ）、 ３．１７（３８，
ｓ）、 ３．８４−３．９３（ＬＨ，ｍ）、 ４．０８
（ＩＨ，ｄｄ、Ｊ＝６１０Ｈｚ）、 ４．１５（ＩＨ，
ｄｄ、Ｊ＝５．１０Ｈｚ）、 ７．０１（ＩＨ，ｄＪ＝
９Ｈｚ）、 ７．１７−７．３１（５Ｈ，ｍ）（Ｒ）
−２−（Ｎ−ｔ−ブトキシカルボニル）アミノ−１−（
メタンスルホニル）オキシ−３−フェニルプロパン収率
：９５％
融 点： １１６−１１７°Ｃ（分解）（ｃｒ） ”
＝ ＋ １８．０ （ｃ＝１． ＣＨＣｌａ）（Ｒ）
−２−（Ｎ−ｔ−ブトキシカルボニル）アミノ−２−フ
ェニル−１−（メタンスルホニル）オキシエタン収率：
９８％
融点： １０７−１０９°Ｃ
（ａ ） ”＝ １１．２ （ｃ＝１． ＣＨＣＩｓ
）ＮＭＲ（ＤＭＳＯ−ｄ、） ： １．３８（９Ｂ、
ｓ）、 ３．１５（３８，ｓ）。(R)-24N-t-butoxycarbonyl)amino-1
-(Methanesulfonyl)oxypropane Yield: 98% Melting point: 75-76°C (decomposition) (αll ”= +29.9 (C=L CHCl3
)(S) -2-(N-t-butoxycarbonyl)amino-1-(methanesulfonyl)oxy-3-methylbutane Yield: 89% Melting point: 75-77°C (decomposition) [α) ”= 34 .9 (c=l, CHCh)N
MR (DMSO-dJ: 0.84 (3H, d, J
=7Hz), 0.87 (3H, d, J=7Hz),
1.39 (9H, s), 1.75 (IH, dqq, J
=7°7,7Hz), 3.16 (3H,s), 3.
50 (IO, dddd, J=4.77, 9Hz), 4
．． 07 (IH, dd, J=7.10Hz), 4.18
(18°dd, J=4.19Hz), 6.91 (18
, d, J=9Hz) (R) -2-(N-t-butoxycarbonyl)amino-1-(methanesulfonyl)oxy-3-methylbutane Yield: 90% Melting point: 73-75°C (decomposition) [α) ”= +33.0 (c=L CHCl3)(
S) -2-(N-t-butoxycarbonyl)amino-
1-(Methanesulfonyl)oxy-4-methylpentane Yield: 97% Melting point: 82-83°C [α) ”= 32.7 (c=1.CHCh)(
S) -2-(N-t-butoxycarbonyl)amino-
1-(methanesulfonyl)oxy-3-phenylpropane Yield: 93% Melting point: 116-117°C (decomposition) Cα, 1”
= 17.4 (C=L C)HCl3)NMR(D
MSO-d6): 1.31 (9H, s), 2.
67 (IH, ddJ=9 14Hz), 2.79 (L
H, dd, J=5.14flz), 3.17(38,
s), 3.84-3.93 (LH, m), 4.08
(IH, dd, J=610Hz), 4.15 (IH,
dd, J=5.10Hz), 7.01(IH, dJ=
9Hz), 7.17-7.31 (5H, m) (R)
-2-(N-t-butoxycarbonyl)amino-1-(
Methanesulfonyl)oxy-3-phenylpropane Yield: 95% Melting point: 116-117°C (decomposition) (cr)
= + 18.0 (c=1.CHCla)(R)
-2-(N-t-butoxycarbonyl)amino-2-phenyl-1-(methanesulfonyl)oxyethane yield:
98% Melting point: 107-109°C (a)''= 11.2 (c=1.CHCIs
) NMR (DMSO-d, ): 1.38 (9B,
s), 3.15 (38, s).
４．２４（ＩＨ，ｄｄ、Ｊ＝８．１０Ｈｚ）、 ４．２
７（１８，ｄｄ、Ｊ＝５．５゜ＩＨｚ）、 ４．８５−
４．９１（ＩＨ，ｗ）、 ７．２６−７．４０（５Ｈ，
ｍ）。4.24 (IH, dd, J=8.10Hz), 4.2
7 (18, dd, J=5.5゜IHz), 4.85-
4.91 (IH, w), 7.26-7.40 (5H,
m).
７．６５（ＩＨ，ｄ、Ｊ＝９Ｈｚ）
（Ｓ）−３−ベンジルオキシ−２−（Ｎ−ｔ−ブトキシ
カルボニル）アミノ−１−（メタンスルホニル）オキシ
プロパン（４）２０．６ｇの（Ｓ） −２−（Ｌ ｔ−
ブトキシカルボニル）アミノ−１−（メタンスルホニル
）オキシプロパンを３００−の４Ｎ塩化水素／ジオキサ
ンで室温にて１時間処理した。減圧下に溶媒を溜去した
後、残渣結晶状物をエーテルより濾取し、水酸化ナトリ
ウム上減圧下に乾燥して、１４．２ｇの（Ｓ）−２−ア
ミノ−１−（メタンスルホニル）オキシプロパン塩酸塩
を得た。7.65 (IH, d, J = 9Hz) 20.6 g of (S)-3-benzyloxy-2-(N-t-butoxycarbonyl)amino-1-(methanesulfonyl)oxypropane (4) ) -2-(L t-
Butoxycarbonyl)amino-1-(methanesulfonyl)oxypropane was treated with 300-4N hydrogen chloride/dioxane for 1 hour at room temperature. After distilling off the solvent under reduced pressure, the residual crystalline material was filtered from ether and dried under reduced pressure over sodium hydroxide to give 14.2 g of (S)-2-amino-1-(methanesulfonyl). Oxypropane hydrochloride was obtained.
収率：１００％
融点： １３２−１３３℃
〔α） ”＝＋１０．３ （ｃ＝１． ＤＭＦ）ＮＭＲ
（ＤＭＳＯ−ｄｈ）： １．２５（３Ｈ，ｄ、Ｊ＝７
Ｈｚ）、 ３．３０（３Ｂ、ｓ）、 ３．４９−３．
５８（１Ｂ、ｍ）、 ４．３１（ＩＨ，ｄｄ、Ｊ＝７
゜１１Ｈｚ）、 ８．５３（３Ｂ、ｂｒｓ）同様にして
、以下の化合物を得た。Yield: 100% Melting point: 132-133°C [α)”=+10.3 (c=1.DMF) NMR
(DMSO-dh): 1.25 (3H, d, J=7
Hz), 3.30 (3B, s), 3.49-3.
58 (1B, m), 4.31 (IH, dd, J=7
11 Hz), 8.53 (3B, brs) The following compound was obtained in the same manner.
（Ｓ）−２−アミノ−１−（メタンスルホニル）オキシ
プロパン塩酸塩
収率：９９％
融点： １３５−１３６℃
〔α〕ローー１０．３ （ｃ＝１． ＤＭＦ）（Ｓ）−
２−アミノ−１−（メタンスルホニル）オキシ−３−メ
チルブタン塩酸塩
収 率：９９％
融点： １２６−１２８°Ｃ
〔α） ”−＋６．６ （ｃ＝１． Ｄｔ’ｌＦ）ＮＭ
Ｒ（ＤＭＳＯ−ｄｉ） ： ０．９７（３Ｈ，ｄ、Ｊ
＝７Ｈｚ）、 ０．９９（３１（、ｄ、Ｊ＝７Ｈｚ）、
１．９９（１８，ｄｑｑ、Ｊ＝７．７．７Ｈｚ）、
３．２３３．２８（ＩＩ（、■）、 ３．３Ｈ３Ｈ，ｓ
）、 ４．３４（ＩＨ，ｄｄ、Ｊ＝６゜１１Ｈｚ）、
４．４６（ＬＨ，ｄｄ、Ｊ＝３．１１Ｈｚ）、 ８．４
５（３Ｈ，ｂｒｓ）（Ｒ）−２−アミノ手（メタンスル
ホニル）オキシ−３−メチルブタン塩酸塩
収率：９８％
融点： １２９ ’−１３１”Ｃ
［α］ ”＝ −６，７（ｃ・１． ＤＭＦ）（Ｓ）−
２−アミノ小（メタンスルホニル）オキシ−４−メチル
ペンタン塩酸塩
収率：９８％
融点： １３７−１３８°Ｃ
〔α） ！４＝＋７．０ （ｃ＝１． ＤＭＦ）（Ｓ）
−２−アミノ小（メタンスルホニル）オキシ−３−フェ
ニルプロパン塩酸塩
収率：１００％
融点： １３３−１３４°Ｃ
〔α） ”−＋７．７ （ｃ＝Ｌ ＤＭＦ）ＮＭＲ（Ｄ
ＭＳＯ−ｄＪ ： ２．８９（ＬＨ，ｄｄ、Ｊ＝９．
１４１（ｚ）３．１０（ＩＩ（、ｄｄ、Ｊ＝６． １４
Ｈｚ）、 ’３．２８（３）ｔ、ｓ）、 ３．７２３
．７８（ＩＩ（、ｓ）、 ４．１９（３Ｈ，ｄｄ、Ｊ＝
５．５．１１）１２）、 ４．３４＜ＩＨ，ｄｄ、Ｊ＝
３． １１Ｈｚ）、 ７．２６−７．３９（５）１．
＋ｗ）、 ８．６９（３Ｈ，ｂｒｓ）
（Ｒン−２−アミノ−１−（メタンスルホニルェニルプ
ロパン塩酸塩
収率： １００％
融点： １２８ − １３（１℃
Ｃａ〕”−−７．４ （ｃ＝Ｉ， ＤＭＦ）（Ｒ）−２
−アミノ−２−フェニル−１−（メタンスルホニル）オ
キシエタン塩酸塩
収率：１００％
融点： １４４ − １４６℃
〔α） ”＝ −９．４ （ｃ＝１， ＤＭＦ）ＮＭＲ
（ＤＭＳＯ−ｄＪ ： ３．５６（３Ｈ，ｓ）、
４．５３（ＩＮ ｄｄＪ＝４．５， １１．５Ｈｚ）、
４．６２（１Ｂ，ｄｄ，Ｊ＝７．５， １１．５Ｈｚ
）４、７１（ＩＨ，ｄｄ，Ｊ＝４．５， ７．５Ｈｚ）
、 ７．４０−７．４９（３１（、ｗ）７、６１−７．
６５（２Ｈ．ｍ）、 ９．０９（３Ｈ，ｂｒｓ）（Ｓ
）−２−アミノ−３−ベンジルオキシ−１−（メタンス
ルボニル）オキシプロパン塩酸塩
収率：９７％
融点： １１２ − １１４ ’Ｃ
〔α） ”＝＋３．１ （ｃ＝Ｌ ＤＭＰ）ＮＭＲ（Ｄ
阿５０， ＴＭＳ） ： ３．２８（３Ｈ，ｓ）、
３．６３−３．７４（３）１．ｓ）、 ４．４０
（ＩＨ．ｄｄ．Ｊ＝５． ｌ］Ｈｚ）、 ４．４８
（ＩＨ，ｄｄＪ＝３．５ １１Ｈｚ）、 ４．５５
、４．５６（２Ｈ，ＡＢｑ，Ｊ＝１２Ｈｚ）。(S)-2-Amino-1-(methanesulfonyl)oxypropane hydrochloride Yield: 99% Melting point: 135-136°C [α] Rho 10.3 (c=1.DMF) (S)-
2-Amino-1-(methanesulfonyl)oxy-3-methylbutane hydrochloride Yield: 99% Melting point: 126-128°C [α) ”-+6.6 (c=1.Dt'lF)NM
R (DMSO-di): 0.97 (3H, d, J
=7Hz), 0.99(31(,d,J=7Hz),
1.99 (18, dqq, J=7.7.7Hz),
3.233.28(II(, ■), 3.3H3H,s
), 4.34 (IH, dd, J=6°11Hz),
4.46 (LH, dd, J=3.11Hz), 8.4
5(3H,brs)(R)-2-Aminohand(methanesulfonyl)oxy-3-methylbutane hydrochloride Yield: 98% Melting point: 129'-131"C [α]"=-6,7(c・1.DMF)(S)-
2-Amino (methanesulfonyl)oxy-4-methylpentane hydrochloride Yield: 98% Melting point: 137-138°C [α)! 4=+7.0 (c=1.DMF)(S)
-2-amino small (methanesulfonyl)oxy-3-phenylpropane hydrochloride Yield: 100% Melting point: 133-134°C [α) ”-+7.7 (c=L DMF) NMR (D
MSO-dJ: 2.89 (LH, dd, J=9.
141(z)3.10(II(,dd,J=6.14
Hz), '3.28(3)t,s), 3.723
．． 78(II(,s), 4.19(3H, dd, J=
5.5.11)12), 4.34<IH, dd, J=
3. 11Hz), 7.26-7.39(5)1.
+w), 8.69 (3H, brs) (Rn-2-amino-1-(methanesulfonylenylpropane hydrochloride) Yield: 100% Melting point: 128 - 13 (1°C Ca)'' - 7.4 ( c=I,DMF)(R)-2
-Amino-2-phenyl-1-(methanesulfonyl)oxyethane hydrochloride Yield: 100% Melting point: 144-146°C [α)”=-9.4 (c=1, DMF) NMR
(DMSO-dJ: 3.56 (3H, s),
4.53 (IN ddJ=4.5, 11.5Hz),
4.62 (1B, dd, J=7.5, 11.5Hz
)4, 71 (IH, dd, J=4.5, 7.5Hz)
, 7.40-7.49 (31(,w)7, 61-7.
65 (2H.m), 9.09 (3H, brs) (S
)-2-Amino-3-benzyloxy-1-(methanesulfonyl)oxypropane hydrochloride Yield: 97% Melting point: 112-114 'C [α)''=+3.1 (c=L DMP) NMR ( D
A50, TMS): 3.28 (3H, s),
3.63-3.74 (3) 1. s), 4.40
(IH.dd.J=5.l]Hz), 4.48
(IH, ddJ=3.5 11Hz), 4.55
, 4.56 (2H, ABq, J=12Hz).
７、２８−７．４Ｈ５Ｌｓ）、８．６３（３Ｈ，ｂｓ）
（５）７．５９ｇの（５）−２−アミノ−１−（メタン
スルホニル）オキシプロパン塩酸塩と７．５６ｇの亜硫
酸ナトリウムを水に溶かし、室温で２０時間かき混ぜた
．反応混合物を強酸性イオン交換樹脂に通し、溶出液を
減圧下に溜去して析出した結晶を再び水に溶かした．こ
れを強塩基性イオン交換樹脂に通した後、減圧下に水を
溜去して析出した白色結晶にエタノールを加えて濾取し
、４．５６ ｇの（Ｓン−２−アミノプロパン−１−ス
ルホン酸を得た。7, 28-7.4H5Ls), 8.63 (3H, bs)
(5) 7.59 g of (5)-2-amino-1-(methanesulfonyl)oxypropane hydrochloride and 7.56 g of sodium sulfite were dissolved in water and stirred at room temperature for 20 hours. The reaction mixture was passed through a strongly acidic ion exchange resin, the eluate was distilled off under reduced pressure, and the precipitated crystals were dissolved again in water. After passing this through a strongly basic ion exchange resin, the water was distilled off under reduced pressure, and ethanol was added to the precipitated white crystals, which were collected by filtration. -Sulfonic acid was obtained.
収率：８２％
融点：＞３３０℃
〔α） ”＝ ＋１８．５ （ｃ＝Ｉ， ＨｚＯ）元素
分析： Ｃ ｓ Ｈ ？ Ｎ Ｏ ｓ Ｓとして０％
Ｈ％ Ｎ％
計算値： ２５．８９ ６．５２ １０．１
６実測値： ２６．１１ ６．８６ １０
．２５ＮＭＲ （０．２ＮＮａＯＯ， ｔ−ＢｕＯＤ）
： １．１５（３Ｌｄ。Yield: 82% Melting point: >330°C [α) ”= +18.5 (c=I, HzO) Elemental analysis: C s H ? 0% as N O s S
H% N% Calculated value: 25.89 6.52 10.1
6 Actual value: 26.11 6.86 10
．． 25NMR (0.2NNaOO, t-BuOD)
: 1.15 (3Ld.
Ｊ＝６．５Ｈ２）、 ２．８６（ＩＨ，ｄｄ，Ｊ＝８．
１４Ｈｚ）、 ２．９７（１）１。J=6.5H2), 2.86(IH, dd, J=8.
14Hz), 2.97(1)1.
ｄｄ，Ｊ＝４． １４Ｈｚ）、 ３．３１−３．３９（
ＩＩ，ｍ）同様にして、以下の化合物を得た。dd, J=4. 14Hz), 3.31-3.39(
II, m) In the same manner, the following compounds were obtained.
（１？）−２−アミノプロパン−１−スルホン酸収率：
６７％
融点：＞３３０″Ｃ
Ｃａ） ”＝ １８．３ （ｃ−１． ＨｚＯ）元素
分析： Ｃ ３ Ｈ ９ Ｎ Ｏ ｓ Ｓとして０％
Ｈ％ Ｎ％
計算値： ２５．８９ ６．５２ １０．１
６実ｆｉ（ａ ： ２６．０３ ６．８０
１０．４０（Ｓ）−２−アミノ−３−メチルブタン−
１−スルホン酸収率：８９％
融 点：３２５℃（分解）
〔α） ”＝ ＋２９．８ （ｃ＝１， ＨｚＯ”）元
素分析： Ｃ ｓ Ｈ １３Ｎ Ｏ ｓ Ｓとして０
％ Ｈ％
計算値： ３５．９１ ７．８４実測値：
３５．９４ ７．９８Ｎ Ｍ Ｒ （０．２Ｎ
ＮａＯＤ， ｔ−ＢｕＯＤ） ：Ｊ＝７８２）、 ０
．９０（３Ｈ．ｄ．Ｊ＝７Ｈｚ）。(1?)-2-aminopropane-1-sulfonic acid yield:
67% Melting point: >330″C Ca)” = 18.3 (c-1.HzO) Elemental analysis: 0% as C3H9NOsS
H% N% Calculated value: 25.89 6.52 10.1
6 real fi(a: 26.03 6.80
10.40(S)-2-amino-3-methylbutane-
1-Sulfonic acid yield: 89% Melting point: 325°C (decomposition) [α) ”= +29.8 (c=1, HzO”) Elemental analysis: 0 as C s H 13N O s S
%H% Calculated value: 35.91 7.84 Actual value:
35.94 7.98N M R (0.2N
NaOD, t-BuOD): J=782), 0
．． 90 (3H.d.J=7Hz).
２、７６（１１，ｄｄ，Ｊ＝９．５， １４．５Ｈｚ）
。2,76 (11,dd, J=9.5, 14.5Hz)
.
（Ｒ）−２−アミノ−３−メチルプタンーエ収率：６７
％
融 点：３２５℃（分解）
Ｎ％
８、３８
８、１９
０、８９（３１（、ｄ
１、６６−１．７８（ｌｔｌ，＋ｗ）。(R)-2-Amino-3-methylputane Yield: 67
% Melting point: 325°C (decomposition) N% 8, 38 8, 19 0, 89 (31 (, d 1, 66-1.78 (ltl, +w).
３、０３−３．０９（２Ｈ，ｍ）
スルホン酸
（α） ”＝ ２９．７ （ｃ＝Ｌ ＨｚＯ）元素
分析： Ｃ，Ｈ．、ＮＯ，Ｓとして０％ Ｈ％
Ｎ％
計算値： ３５．９］ ７．８４ ８．３
８実測（ｉｆ ： ３５．９６ ７．９１
８．７０（Ｓ）−２−アミノ−４−メチルペンタン−
１−スルホン酸融点：＞３００°Ｃ
Ｃａ） ”＝＋１５．５ （ｃ＝１， Ｈ．Ｏ）ＮＭＲ
（０．２ＮＮａＯＤ． ｔ−ＢｕＯＤ） ： ０
．８９（３Ｈ，ｄ。3, 03-3.09 (2H, m) Sulfonic acid (α) ” = 29.7 (c = L HzO) Elemental analysis: 0% as C, H., NO, S H%
N% Calculated value: 35.9] 7.84 8.3
8 actual measurement (if: 35.96 7.91
8.70(S)-2-amino-4-methylpentane-
1-Sulfonic acid melting point: >300°C Ca) ”=+15.5 (c=1, H.O) NMR
(0.2NNaOD.t-BuOD): 0
．． 89 (3H, d.
Ｊ＝”ｌＨｚ＞、 ０．９０（３Ｈ，ｄ，Ｊ＝７）１ｘ
）、 １．３０（２Ｈ．ｄｄ，Ｊ＝７。J=”lHz>, 0.90 (3H, d, J=7) 1x
), 1.30 (2H.dd, J=7.
７Ｈｚ）、 １．６７（１Ｎ，ｄｑＱ，Ｊ＝７．７．７
）１ｘ）、 ２．７８（１）１，ｄｄ。7Hz), 1.67 (1N, dqQ, J=7.7.7
)1x), 2.78(1)1,dd.
Ｊ＝ＩＨ．ｄｄ，Ｊ＝９． １４Ｈｚ）、 ３．０１（
ＩＨ．ｄｄ，Ｊ＝３． １４８２）３、２９（ＩＨ，ｄ
ｄｔ．Ｊ＝３． ９， ７Ｌｚ）（Ｓ）−２−アミ八３
ーフェニルプロパンー１ースルホン酸収率ニア２％
融点：＞３３０℃
（ａ’Ｊ ”＝ ３．５ （ｃ＝１， ＨｚＯ）元素
分析： Ｃ ９ Ｈ Ｉｘ Ｎ Ｏ ｘ Ｓとして０
％ Ｈ％ Ｎ％
計算値： ５０．２２ ６．０９ ６．
５１実測値： ５０．４４ ６．３０ ６
．３ＯＮＭＲ （０．２ＮＮａＯ口， ｔ−ＢｕＯ
Ｄ） ： ２．６Ｂ＜ＩＨ，ｄｄ。J=IH. dd, J=9. 14Hz), 3.01(
IH. dd, J=3. 1482) 3, 29 (IH, d
dt. J=3. 9, 7Lz)(S)-2-ami83
-Phenylpropane-1-sulfonic acid Yield near 2% Melting point: >330°C (a'J''= 3.5 (c=1, HzO) Elemental analysis: 0 as C 9 H Ix N O x S
% H% N% Calculated value: 50.22 6.09 6.
51 actual measurement value: 50.44 6.30 6
．． 3ONMR (0.2NNaO, t-BuO
D): 2.6B<IH, dd.
Ｊ＝８． １３Ｈｚ）、 ２．８５（ＩＦＩ，ｄｄ，Ｊ
＝９． １４Ｈｚ）、 ２．８６（ＩＨ，ｄｄ、Ｊ＝５
．５．１３Ｈｚ）、 ３．０５（Ｉｌｌ、ｄｄ、Ｊ＝３
．１４Ｈｚ）。J=8. 13Hz), 2.85(IFI, dd, J
=9. 14Hz), 2.86 (IH, dd, J=5
．． 5.13Hz), 3.05(Ill, dd, J=3
．． 14Hz).
３．４８−３．５５（ＩＨ，ｓ）、 ７．２８−７．
４Ｈ５Ｌｍ）（Ｒ）−２−アミ八３−フェニルプロパン
小スルホン酸収率：８３％
融点：＞３３０°Ｃ
〔α） ”＝＋３．６ （ｃ・Ｌ ＨｚＯ）元素分析：
ＣｌＨ，、ＮＯ，Ｓとして０％ ８％ Ｎ％
計算値： ５０．２２ ６．０９ ６．５１実
測値： ５０．０３ ６．３８ ６．４５（Ｒ
）−２−アミ八２−フェニルエタン小スルホン酸収率ニ
ア９％
融点：＞３３０℃
〔α〕３％−＋ １．３ （ｃｍｌ、 ＨｚＯ）元素分
析： Ｃ，Ｈ，、ＮＯ，Ｓとして０％ ８％ Ｎ
％
計算値： ４７．７５ ５．５１ ６．９６
実測値： ４７．８０ ５．４４ ６．９６Ｎ
ＭＲ（０，２ＮＮａＯＤ、 ｔ−ＢｕＯＤ） ： ３
．２３（１８，ｄｄ。3.48-3.55 (IH, s), 7.28-7.
4H5Lm) (R)-2-Ami8 3-phenylpropane small sulfonic acid Yield: 83% Melting point: >330°C [α)”=+3.6 (c・L HzO) Elemental analysis:
0% 8% N% as ClH,, NO, S Calculated value: 50.22 6.09 6.51 Actual value: 50.03 6.38 6.45 (R
)-2-Ami8 2-phenylethane Small sulfonic acid yield near 9% Melting point: >330℃ [α]3%-+ 1.3 (cml, HzO) Elemental analysis: as C, H,, NO, S 0% 8% N
% Calculated value: 47.75 5.51 6.96
Actual value: 47.80 5.44 6.96N
MR (0,2NNaOD, t-BuOD): 3
．． 23 (18, dd.
Ｊ＝１０．１３Ｈｚ）、 ３．４３（ＬＨ，ｄｄ、Ｊ＝
５．５．１３）１ｚ）。J=10.13Hz), 3.43(LH, dd, J=
5.5.13) 1z).
４．０８（１８，ｄｄ、Ｊ＝５．５．１０Ｈｚ）、 ７
．４０−７．４６（５Ｈ，＋＋）（Ｓ）−２−アミノ−
３−ベンジルオキシプロパン−１−スルホン酸
収 率ニア６％
融点： ２４２−２４３°Ｃ
Ｃα） ｚ５＝−８，４（Ｃ，１，ＨｚＯ）元素分析：
Ｃ，、Ｈ，、ＮＯ，Ｓとして０％ ８％ Ｎ％
計算値： ４８．９７ ６．１６ ５．７１
実測値： ４Ｂ、９５ ５．８８ ５．７８
ＮＭＲ（０，２ＮＮａＯＤ、 ｔ−ＢｕＯＤ） ：
２．８３（ＬＨ，ｄｄＪ＝８ １４Ｈｚ）、 ３．０５
（ＩＨ，ｄｄ、Ｊ＝３．５．１４Ｈｚ）。4.08 (18, dd, J=5.5.10Hz), 7
．． 40-7.46(5H,++)(S)-2-amino-
3-benzyloxypropane-1-sulfonic acid Yield near 6% Melting point: 242-243°C Cα) z5=-8,4(C,1,HzO) Elemental analysis:
0% as C,,H,,NO,S 8% N% Calculated value: 48.97 6.16 5.71
Actual value: 4B, 95 5.88 5.78
NMR (0,2N NaOD, t-BuOD):
2.83 (LH, ddJ=8 14Hz), 3.05
(IH, dd, J=3.5.14Hz).
３．４２−３．５１（２８，ｍ）、 ３．５５−３．６
１（１８，ｍ）。3.42-3.51 (28, m), 3.55-3.6
1 (18, m).
４．５９（２８，ｓ）、 ７．３６−７．４６（５Ｈ，
ｗ）実施例２゜
９．８１ ｇの（Ｓ）−２−アミ八３−ベンジｌレオキ
シブロノ々ンートスルホン酸を水、酢酸、メタノールの
混合溶媒１４０−に溶かし、１ｇの１０％ツクラジウム
−炭素の存在下、常圧室温にて２０時間接触還元を１〒
つだ。触媒を濾去した後、濾液を減圧下Ｇこ溜去した。4.59 (28, s), 7.36-7.46 (5H,
w) Example 2: Dissolve 9.81 g of (S)-2-amino-3-benzyl-leoxybronobentosulfonic acid in a mixed solvent of water, acetic acid, and methanol, and add 1 g of 10% Tsucladium-carbon. Catalytic reduction for 20 hours at normal pressure and room temperature in the presence of
One. After removing the catalyst by filtration, the filtrate was distilled off under reduced pressure.
残渣にトルエンを加えて減圧下で溜去することにより、
残留する酢酸を共沸除去した。析出した白色結晶をエタ
ノールを加えて濾取した。これをエタノール水より再結
晶して４．３９ｇの（Ｓ）−２−アミノ−３−ヒドロキ
シプロパン−トスルホン酸を得た。By adding toluene to the residue and distilling it off under reduced pressure,
Residual acetic acid was removed azeotropically. The precipitated white crystals were collected by filtration after adding ethanol. This was recrystallized from ethanol water to obtain 4.39 g of (S)-2-amino-3-hydroxypropane-tosulfonic acid.
収 率ニア９％
融 点： ２７９−２８１°Ｃ（分解）［α］ ”＝
＋’ｙ、ｓ （Ｃ＝１． ８２０）元素分析：
Ｃｓ Ｈ＊ Ｎ Ｏ４Ｓとして０％ ８％ Ｎ％
計算値： ２３．２２ ５．８４ ９．０３
実測値： ２３．５０ ６．１４ ８．９１Ｎ
ＭＲ（０，２ＮＮａＯＤ ｔ−ＢｕＯＤ） ： ２．
８３（ＩＨ，ｄｄＪ＝９．１４Ｈｚ）、 ３．０７（１
８，ｄｄ、Ｊ＝３．５． ｌ１ｚ）。Yield near 9% Melting point: 279-281°C (decomposition) [α] ”=
+'y, s (C=1.820) Elemental analysis:
Cs H* N 0% 8% N% Calculated value: 23.22 5.84 9.03
Actual value: 23.50 6.14 8.91N
MR (0,2N NaOD t-BuOD): 2.
83 (IH, ddJ=9.14Hz), 3.07 (1
8, dd, J=3.5. l1z).
３．２３−３．３４（ＩＨ，ｍ）、 ３．５１（ＩＨ，
ｄｄ、Ｊ＝６．５．１１Ｈｚ）。3.23-3.34 (IH, m), 3.51 (IH,
dd, J=6.5.11Hz).
３．５８（ＩＨ，ｄｄ、Ｊ＝５．５．１１Ｈｚ）実施例
３゜
４．３５ｇの（Ｓ）−２−アミノ−１−（メタンスルホ
ニル）オキシ−３−メチルブタンと４．０２ｇの亜硫酸
アンモニウムを水に溶かし、室温で２０時間かき混ぜた
０反応混合物を、強酸性イオン交換樹脂に通し、溶出液
を減圧下に溜去して析出した結晶を再び水に溶かした。3.58 (IH, dd, J = 5.5.11 Hz) Example 3 4.35 g of (S)-2-amino-1-(methanesulfonyl)oxy-3-methylbutane and 4.02 g of ammonium sulfite was dissolved in water and stirred at room temperature for 20 hours. The reaction mixture was passed through a strongly acidic ion exchange resin, the eluate was distilled off under reduced pressure, and the precipitated crystals were dissolved in water again.
これを強塩基性イオン交換樹脂に通した後、減圧下に水
を溜去して析出した白色結晶にエタノールを加えて濾取
し、２．８７ｇの（Ｓ）−２−アミノ−３−メチルブタ
ン−１−スルホン酸を得た。After passing this through a strongly basic ion exchange resin, the water was distilled off under reduced pressure, and ethanol was added to the precipitated white crystals, which were collected by filtration. -1-sulfonic acid was obtained.
収率：８６％
実施例４゜
（１）１３．２ｇの（Ｓ） −２−（Ｎ−ｔ−ブトキシ
カルボニル）アミノ−１−（メタンスルホニル）オキシ
−３−メチルブタンとと１２．３ｇの臭化リチウムを１
００−の無水アセトンに溶かし、室温で２０時間かき混
ぜた。水、５％炭酸水素ナトリウム水溶液、飽和食塩水
で順次洗浄した後、硫酸ナトリウム上で乾燥した。溶媒
を減圧下で溜去し、得られた粗生成物をシリカゲルカラ
ムクロマトグラフィーで精製して７．１９ｇの（Ｓ）
−２−（Ｎ−ｔ−ブトキシカルボニル）アミノ−１−ブ
ロモ−３−メチルブタンを得た。Yield: 86% Example 4゜(1) 13.2 g of (S)-2-(Nt-butoxycarbonyl)amino-1-(methanesulfonyl)oxy-3-methylbutane and 12.3 g of odor 1 lithium chloride
00- in anhydrous acetone and stirred at room temperature for 20 hours. After sequentially washing with water, 5% aqueous sodium hydrogen carbonate solution, and saturated brine, it was dried over sodium sulfate. The solvent was distilled off under reduced pressure, and the resulting crude product was purified by silica gel column chromatography to yield 7.19 g of (S).
-2-(N-t-butoxycarbonyl)amino-1-bromo-3-methylbutane was obtained.
収率：５７％
融点： Ｔｏ −７１°Ｃ
（ａ ） ”−３５，６（ｃｍｌ、 ＣＩＣｌＣｌ５）
Ｎ （ＤＭＳＯ−ｄｉ） ： ０．８４（６）１．
ｔ、Ｊ＝７Ｈｚ）、 １．３９（９Ｂ、ｓ）、 １．
７２−１．８４（ＩＨ，−）、 ３．４０−３．４９
（２Ｂ、ｍ）３．５４−３．６１（ＩＨ４）、 ６．８
４（ＩＨ，ｄ、Ｊ＝８Ｈｚ）（２）６．１２ｇの（Ｓ）
−２−（Ｎ−ｔ−ブトキシカルボニル）アミノ−１−
ブロモ−３−メチルブタンと４Ｎ塩化水素／ジオキサン
を室温で１時間かき混ぜた。溶媒を減圧下に溜去し、析
出した結晶をエタノールを加えて濾取し、４．３７ｇの
（Ｓ）−２−アミノ−１−ブロモー３−メチルブタン塩
酸塩を得た。Yield: 57% Melting point: To -71°C (a)''-35,6 (cml, CIClCl5)
N (DMSO-di): 0.84(6)1.
t, J=7Hz), 1.39 (9B, s), 1.
72-1.84 (IH, -), 3.40-3.49
(2B, m) 3.54-3.61 (IH4), 6.8
4 (IH, d, J = 8 Hz) (2) 6.12 g of (S)
-2-(N-t-butoxycarbonyl)amino-1-
Bromo-3-methylbutane and 4N hydrogen chloride/dioxane were stirred at room temperature for 1 hour. The solvent was distilled off under reduced pressure, and the precipitated crystals were collected by filtration after adding ethanol to obtain 4.37 g of (S)-2-amino-1-bromo-3-methylbutane hydrochloride.
収 率：９４％
融 点： ２０８−２０９℃（分解）
〔α） ”＝＋１７．０ （ｃ・１． ＨｚＯ）Ｎ
ＭＲ（ＤＭＳＯ−ｄＪ ： ０．９４（３Ｈ，ｄ、Ｊ
＝７Ｈｚ）、０．９９（３Ｈ，ｄ、Ｊ＝７Ｈｚ）
１．９５−２．０７（ＩＨ，ｍ）、 ３．１５−３．
２２（ＩＨ，ｍ）、 ３．７５（ＩＨ，ｄｄ、Ｊ＝５
． １１Ｈｚ）、 ３．８９（ＬＨ，ｄｄ。Yield: 94% Melting point: 208-209℃ (decomposition) [α)”=+17.0 (c・1.HzO)N
MR (DMSO-dJ: 0.94 (3H, d, J
=7Hz), 0.99 (3H, d, J=7Hz)
1.95-2.07 (IH, m), 3.15-3.
22 (IH, m), 3.75 (IH, dd, J=5
．． 11Hz), 3.89 (LH, dd.
Ｊ＝４．１１Ｈｚ）、８．５１（３８，ｂｒｓ）（３）
３．４４ｇの（Ｓ）−２−アミノ−１−ブロモ−３−メ
チルブタン塩酸塩と３．２１ ｇの亜硫酸ナトリウムを
水に溶かし、室温で２０時間かき混ぜた０反応混合物を
、強酸性イオン交換樹脂に通し、溶出液を減圧下に溜去
して析出した結晶を再び水に溶かした。これを強塩基性
イオン交換樹脂に通した後、減圧下に水を溜去して析出
した白色結晶にエタノールを加えて濾取し、２．５２ｇ
の（Ｓ）−２−アミノ−３−メチルブタン−１−スルホ
ン酸を得た（収率：８９％）。J=4.11Hz), 8.51(38,brs)(3)
3.44 g of (S)-2-amino-1-bromo-3-methylbutane hydrochloride and 3.21 g of sodium sulfite were dissolved in water and stirred at room temperature for 20 hours. The reaction mixture was then treated with a strongly acidic ion exchange resin. The eluate was distilled off under reduced pressure, and the precipitated crystals were again dissolved in water. After passing this through a strongly basic ion exchange resin, the water was distilled off under reduced pressure, ethanol was added to the precipitated white crystals, and 2.52 g was collected by filtration.
(S)-2-amino-3-methylbutane-1-sulfonic acid was obtained (yield: 89%).
同様にして、 （Ｒ）−２−アミノ−３−メチルブタン
−１スルホン酸を得た（収率：６７％）。Similarly, (R)-2-amino-3-methylbutane-1 sulfonic acid was obtained (yield: 67%).
実施例５゜
（１）アルゴン雰囲気下、６．５２ｇの（２Ｓ、３Ｒ）
−２−ベンジルオキシカルボニルアミノ−３−メチルペ
ンタノールと８．６６ ｇのトリフェニルホスフィンの
テトラヒドロフラン溶液１５０ｍを水浴にて冷却し、５
．２ｄのジエチルアゾジカルボキシレート、２．４ｄの
チオ酢酸を順次加えた。水冷下に２時間、室温で２０時
間かき混ぜた後、溶媒を減圧下に溜去した。残渣をシリ
カゲルカラムクロマトグラフィーで精製して、７．２５
ｇの（２Ｓ、３Ｒ） −２−（Ｎ−ベンジルオキシカル
ボニル）アミノ−３メチルペンチルエタンチオエートを
白色結晶として得た。Example 5゜(1) Under argon atmosphere, 6.52 g of (2S, 3R)
150 ml of a tetrahydrofuran solution of -2-benzyloxycarbonylamino-3-methylpentanol and 8.66 g of triphenylphosphine was cooled in a water bath, and
．． 2d of diethyl azodicarboxylate and 2.4d of thioacetic acid were added sequentially. After stirring for 2 hours under water cooling and 20 hours at room temperature, the solvent was distilled off under reduced pressure. The residue was purified by silica gel column chromatography to give 7.25
g of (2S,3R)-2-(N-benzyloxycarbonyl)amino-3methylpentylethanethioate was obtained as white crystals.
収率：９０％
融点： ７４−７５℃
（（ｒ ） ” ＝ １０．４ （ｃ＝Ｌ ＣＨＣｌ
＋）元素分析’ Ｃ＋ｈＨｚｓＮＯｚＳとして０％
６％ Ｎ％
計算値： ６２．１１ ７．４９ ４．５４実
測値： ６２．０８ ７．５５ ４．４８ＮＭ
Ｒ（ＣＤＣ１ｚ） ： ０．９１（３Ｈ，ｔ、Ｊ４Ｈ
ｚ）、 ０．９３（３８，ｄ、Ｊ＝７Ｈｚ）、 １．０
８−１．２０（ＩＨ，ｓ＋）、 １．４７４．６４（２
Ｆ１．ｗ）、 ２．２８Ｃ３Ｈ，ｓ）、 ２．９８（Ｌ
Ｈ，ｄｄ、Ｊ＝９．５゜１４８２）、 ３．０５（１８
，ｄｄ、Ｊ＝４．１４Ｈｚ）、 ３．７０（ＩＨ。Yield: 90% Melting point: 74-75°C ((r)” = 10.4 (c=L CHCl
+) Elemental analysis' C+hHzsNOzS 0%
6% N% Calculated value: 62.11 7.49 4.54 Actual value: 62.08 7.55 4.48NM
R (CDC1z): 0.91 (3H, t, J4H
z), 0.93 (38, d, J=7Hz), 1.0
8-1.20 (IH, s+), 1.474.64 (2
F1. w), 2.28C3H,s), 2.98(L
H, dd, J=9.5°1482), 3.05(18
, dd, J=4.14Hz), 3.70 (IH.
ｄｄｄｄ、Ｊ＝４．６．９．５．９．５Ｈ２）、 ４．
７８（ＩＨ，ｄ。dddd, J=4.6.9.5.9.5H2), 4.
78 (IH, d.
Ｊ＝９．５Ｈ２）、 ５．０５ ａｎｄ ５．１２（２
８，ＡＢｑ、Ｊ＝１２Ｈｚ）。J=9.5H2), 5.05 and 5.12(2
8, ABq, J=12Hz).
７．２８−７．４０（５Ｂ、−） 同様にして、以下の化合物を得た。7.28-7.40 (5B, -) Similarly, the following compounds were obtained.
（Ｓ） −２−（Ｎ−ｔ−ブトキシカルボニル）アミノ
−３−（４’−ベンジルオキシ）フェニルプロピルエタ
ンチオエート収率ニア４％
融点： １２４−１２５°Ｃ
（α〕”＝＋３．６ （Ｃ＝１． ＣＨＣｌ３）元素分
析”ＣｚｉＨｚ＊ＮＯ−３として０％ ６％ Ｎ％
計算値： ６６．４８ ７．０３ ３．３７
実測値： ６６．６７ ７．１８ ３．３２
ＮＭＲ（ＣＤＣ１３） ： １．４１（９Ｈ，ｓ）、
２．３６（３Ｈ，ｓ）。(S) -2-(N-t-butoxycarbonyl)amino-3-(4'-benzyloxy)phenylpropylethanethioate Yield near 4% Melting point: 124-125°C (α)"=+3.6 (C=1. CHCl3) Elemental analysis "CziHz*0% 6% N% as NO-3 Calculated value: 66.48 7.03 3.37
Actual value: 66.67 7.18 3.32
NMR (CDC13): 1.41 (9H, s),
2.36 (3H, s).
２．７１（１Ｂ、ｄｄ、Ｊ＝７．１４Ｈｚ）、 ２．８
４（１８，ｄｄ、Ｊ＝６゜１４Ｈｚ）、 ２．９２（Ｉ
Ｈ，ｄｄ、Ｊ＝８．１４Ｈｚ）、 ３．０６（ＩＨ，ｄ
ｄ。2.71 (1B, dd, J=7.14Hz), 2.8
4 (18, dd, J = 6° 14Hz), 2.92 (I
H, dd, J = 8.14Hz), 3.06 (IH, d
d.
Ｊ＝５． １４Ｈｚ）、 ３．８８−３．９８（１８
４）、 ４．６０（ＩＦＩ、ｄ。J=5. 14Hz), 3.88-3.98(18
4), 4.60 (IFI, d.
Ｊ＝８Ｈｚ）、 ５．０３（２Ｈ，ｓ）、 ６．９１（
２Ｈ，ｄ、Ｊ＝８Ｈｚ）７．１０（２８，ｄ、Ｊ＝８Ｈ
ｚ）、 ７．２９−７．４４（５Ｂ、ｍ）（２Ｓ、 ３
Ｒ）−３−ベンジルオキシ−２−（Ｎ−ｔ−ブトキシカ
ルボニル）アミノブチルエタンチオエート収率：９７％
融 点： 油状物
〔α） ”−＋１１．０ （ｃ＝１． ＣＨＧｌ＋）Ｎ
ＭＲ（ＣＤＣＩｓ） ： １．２１（３８，ｄ、Ｊ＝
６Ｈｚ）、 １．４３（９Ｂ、ｓ）、 ２．３３（３
１，ｓ）、 ３．６５−３．７５（２１，ｍ）、
４．４０ａｎｄ ４．６０（２■、ＡＢｑ＋Ｊ＝１１．
５Ｈｚ）、４．８７（１８，ｄ。J=8Hz), 5.03(2H,s), 6.91(
2H, d, J = 8Hz) 7.10 (28, d, J = 8H
z), 7.29-7.44 (5B, m) (2S, 3
R)-3-benzyloxy-2-(N-t-butoxycarbonyl)aminobutylethanethioate Yield: 97% Melting point: Oil [α)''-+11.0 (c=1.CHGl+)N
MR (CDCIs): 1.21 (38, d, J=
6Hz), 1.43 (9B, s), 2.33 (3
1,s), 3.65-3.75(21,m),
4.40and 4.60 (2■, ABq+J=11.
5Hz), 4.87 (18, d.
Ｊ＝９．５Ｈ２）、 ７．２７−７．３９（５１１，＋
＋）（２）１８ ｄの３０％過酸化水素水と１８０１ｄ
の９８％蟻酸を室温で１時間かき混ぜて過蟻酸溶液を調
製した。これを水浴にて冷却し、９．２８ｇの（２Ｓ、
３Ｒ） −２−（Ｎ−ヘア ’、；ルオキシカルボニ
ル）アミノ−３−メチルペンチルエタンチオエートの蟻
酸溶液４（ｌｄを３０分かけて滴下した。J=9.5H2), 7.27-7.39(511,+
+) (2) 18 d of 30% hydrogen peroxide solution and 1801 d
A performic acid solution was prepared by stirring 98% formic acid at room temperature for 1 hour. This was cooled in a water bath, and 9.28 g of (2S,
3R) -2-(N-hair',;ruoxycarbonyl)amino-3-methylpentylethanethioate in formic acid solution 4 (ld) was added dropwise over 30 minutes.
水冷下に２時間、室温で２０時間がき混ぜた後、０．５
ｇの１０％パラジウム−炭素を加えて過剰の過酸化物を
分解した。０．５ｇのパラジウム−炭素をさらに加え、
水素雰囲気下に１０時間がき混ぜた。触媒を濾去した後
、濾液を減圧下に溜去して３．９７ｇの（２Ｓ、３Ｒ）
２−アミ／−３−メチルベンタンートスルボン酸を白色
結晶として得た。After stirring for 2 hours under water cooling and 20 hours at room temperature, 0.5
g of 10% palladium on carbon was added to destroy excess peroxide. Add another 0.5 g of palladium-carbon;
Stirred under hydrogen atmosphere for 10 hours. After filtering off the catalyst, the filtrate was distilled off under reduced pressure to obtain 3.97 g of (2S, 3R).
2-Ami/-3-methylbentantosulfonic acid was obtained as white crystals.
収率ニア３％
融点： ２９２−２９３℃
［α］”＝＋２４．８ （ｃ＝１．ＨｚＯ）元素分析：
Ｃ，Ｈ，５ＮＯ３Ｓとして０％ ６％ Ｎ％
計算値： ３９．７６ ８．３４ ７．７３
実測値： ３９．８１ Ｂ、５２ ７．６２
ＮＭＲ（０，２Ｎ Ｎａ０Ｄ、 ｔ−ＢｕＯＤ） ：
０．８６（３８ｄＪ＝７．５Ｈｚ）、 ０．８９（３
Ｈ，ｔ、Ｊ＝７．５Ｈｚ）、 １．１２−１．２４（１
Ｂ、ｍ）、 １．３１−１．４２（１８，ｍ）、
１．４６−１．５７（ＬＨ，ｍ）。Yield near 3% Melting point: 292-293℃ [α]”=+24.8 (c=1.HzO) Elemental analysis:
0% 6% N% Calculated value as C, H, 5NO3S: 39.76 8.34 7.73
Actual value: 39.81 B, 52 7.62
NMR (0,2N Na0D, t-BuOD):
0.86 (38dJ=7.5Hz), 0.89 (3
H, t, J=7.5Hz), 1.12-1.24(1
B, m), 1.31-1.42 (18, m),
1.46-1.57 (LH, m).
２．７５（ＩＨ，ｄｄ、Ｊ＝１０．１５Ｈｚ）、 ３．
０３（ＩＨ，ｄｄ、Ｊ＝２１５）１ｚ）、 ３．１５−
３．２０（１８，ｍ）同様にして、以下の化合物を得た
。2.75 (IH, dd, J=10.15Hz), 3.
03(IH, dd, J=215)1z), 3.15-
The following compound was obtained in the same manner as 3.20 (18, m).
（Ｓ）−２−アミノ−３−（４°−ヒドロキシ）フェニ
ルプロパン−１−スルホン酸
収率ニア９％
融点：＞３３０℃
（α） ”＝ ４．７ （ｃ＝０．５． Ｉｈ０）元
素分析： Ｃｑ Ｈ＋ ｓ Ｎ Ｏａ Ｓとして０％
８％ Ｎ％
計算値： ４６．７５ ５．７６ ６．０６
実測値： ４６．６８ ５．８６ ６．１６
ＮＭＲ（０，２Ｎ Ｎａ０Ｄ、 ｔ−ＢｕＯＤ） ：
２．５０（ＩＨ，ｄｄ。(S)-2-Amino-3-(4°-hydroxy)phenylpropane-1-sulfonic acid Yield near 9% Melting point: >330°C (α) ”= 4.7 (c=0.5. Ih0) Elemental analysis: 0% as Cq H+ s N Oa S
8% N% Calculated value: 46.75 5.76 6.06
Actual value: 46.68 5.86 6.16
NMR (0,2N Na0D, t-BuOD):
2.50 (IH, dd.
Ｊ＝８．１４Ｈｚ）、 ２．６９（ＩＨ，ｄｄ、Ｊ＝５
．５．１４Ｈｚ）、 ２．８３（１１，ｄｄ、Ｊ＝９．
１４Ｈｚ）、 ３．０６（ＬＨ，ｄｄ、Ｊ＝３．１４Ｈ
ｚ）。J=8.14Hz), 2.69(IH, dd, J=5
．． 5.14Hz), 2.83 (11,dd, J=9.
14Hz), 3.06 (LH, dd, J=3.14H
z).
３．３８−３．４５（ＩＨ，簡）、 ６．５６−６．
６１（２Ｆｌ、ｍ）。3.38-3.45 (IH, simplified), 6.56-6.
61 (2 Fl, m).
６．９９−７．０３ （２８，−）
（２３，３Ｒ）−２−アミノ−３−ヒドロキシブタン−
１−スルホン酸
収率：８９％
融点： ２２０−２２２℃
（α） ｔ４＝ ＋１５．５ （ｃ＝１． ＨｔＯ）元
素分析： Ｃａ Ｈ＋ ＋ Ｎ Ｏａ Ｓとして０％
８％ Ｎ％
計算値： ２Ｂ、４０ ６．５５ ８．２８
実測値： ２８．１０ ６．３５ ７．９５Ｎ
ＭＲ（０，２Ｎ Ｎａ０Ｄ ｔ−ＢｕＯＤ）： １
．１７（３Ｈ，ｄ。6.99-7.03 (28,-) (23,3R)-2-amino-3-hydroxybutane-
1-Sulfonic acid yield: 89% Melting point: 220-222°C (α) t4 = +15.5 (c = 1. HtO) Elemental analysis: 0% as Ca H+ + N Oa S
8% N% Calculated value: 2B, 40 6.55 8.28
Actual value: 28.10 6.35 7.95N
MR (0,2N Na0D t-BuOD): 1
．． 17 (3H, d.
Ｊ＝６．５Ｈｚ）、 ２．８３（ＩＨ，ｄｄ、Ｊ＝９
． １４Ｈｚ）、 ３．１０（ＩＩ（ｄｄ、Ｊ＝２．
５． １４Ｈｚ）、 ３．１１’−３，１７（ＩＨ，
ｓ）。J=6.5Hz), 2.83(IH, dd, J=9
．． 14Hz), 3.10(II(dd, J=2.
5. 14Hz), 3.11'-3,17(IH,
s).
３．７７−３．８４（１８ｍ）
（作用及び効果）
前記一般式（１）中のＸがスルホ基である本発明化合物
の植物生育調整作用を調べた結果、本発明化合物が植物
生長調整作用を有することが明らかになった。従って、
本発明化合物は農園芸用薬剤等として有用である。3.77-3.84 (18m) (Action and Effect) As a result of investigating the plant growth regulating effect of the compound of the present invention in which X in the general formula (1) is a sulfo group, it was found that the compound of the present invention has a plant growth regulating effect. It was revealed that the Therefore,
The compounds of the present invention are useful as agricultural and horticultural agents.
Claims (1)
キル基、フェニル基、フェニルアルキル基、ヒドロキシ
アルキル基、ヒドロキシフェニルアルキル基又はフェニ
ルアルキルオキシアルキル基、Ｘはスルホ基、メシル基
、トシル基、アセチルチオ基又はハロゲンを表す。〕 で表される化合物及びその薬学的に許容される塩。(1) The following general formula (I): ▲Mathematical formulas, chemical formulas, tables, etc.▼(I) [In the formula, R is hydrogen or a protecting group for an amino group, Y is a lower alkyl group, phenyl group, phenylalkyl group, hydroxyalkyl group, hydroxyphenylalkyl group or phenylalkyloxyalkyl group; X represents a sulfo group, mesyl group, tosyl group, acetylthio group or halogen; ] A compound represented by these and its pharmaceutically acceptable salt.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP10614890A JP3174566B2 (en) | 1990-04-20 | 1990-04-20 | Aminoalkane derivatives |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP10614890A JP3174566B2 (en) | 1990-04-20 | 1990-04-20 | Aminoalkane derivatives |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPH045270A true JPH045270A (en) | 1992-01-09 |
| JP3174566B2 JP3174566B2 (en) | 2001-06-11 |
Family
ID=14426264
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP10614890A Expired - Fee Related JP3174566B2 (en) | 1990-04-20 | 1990-04-20 | Aminoalkane derivatives |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JP3174566B2 (en) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2007526228A (en) * | 2003-06-23 | 2007-09-13 | ニューロケム （インターナショナル） リミテッド | Methods and compositions for the treatment of amyloid-related diseases and epilepsy-related diseases |
| WO2010014943A2 (en) * | 2008-08-01 | 2010-02-04 | Bioxiness Pharmaceutics, Inc. | Methionine analogs and methods of using same |
-
1990
- 1990-04-20 JP JP10614890A patent/JP3174566B2/en not_active Expired - Fee Related
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2007526228A (en) * | 2003-06-23 | 2007-09-13 | ニューロケム （インターナショナル） リミテッド | Methods and compositions for the treatment of amyloid-related diseases and epilepsy-related diseases |
| WO2010014943A2 (en) * | 2008-08-01 | 2010-02-04 | Bioxiness Pharmaceutics, Inc. | Methionine analogs and methods of using same |
| WO2010014943A3 (en) * | 2008-08-01 | 2011-01-13 | Bioxiness Pharmaceutics, Inc. | Methionine analogs and methods of using same |
| US8580859B2 (en) | 2008-08-01 | 2013-11-12 | Bioxiness Pharmaceuticals, Inc. | Methionine analogs and methods of using same |
| US9695119B2 (en) | 2008-08-01 | 2017-07-04 | Bioxiness Pharmaceuticals, Inc. | Methionine analogs and methods of using same |
Also Published As
| Publication number | Publication date |
|---|---|
| JP3174566B2 (en) | 2001-06-11 |
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