JPS5982091A - バイオプテリンの製法 - Google Patents
バイオプテリンの製法Info
- Publication number
- JPS5982091A JPS5982091A JP19016082A JP19016082A JPS5982091A JP S5982091 A JPS5982091 A JP S5982091A JP 19016082 A JP19016082 A JP 19016082A JP 19016082 A JP19016082 A JP 19016082A JP S5982091 A JPS5982091 A JP S5982091A
- Authority
- JP
- Japan
- Prior art keywords
- biopterin
- reduced
- tetrahydrobiopterin
- dihydrobiopterin
- ascorbic acid
- 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
- LHQIJBMDNUYRAM-UHFFFAOYSA-N L-erythro-Biopterin Natural products N1=C(N)NC(=O)C2=NC(C(O)C(O)C)=CN=C21 LHQIJBMDNUYRAM-UHFFFAOYSA-N 0.000 title claims abstract description 12
- LHQIJBMDNUYRAM-AWFVSMACSA-N D-erythro-biopterin Chemical compound N1=C(N)NC(=O)C2=NC([C@H](O)[C@H](O)C)=CN=C21 LHQIJBMDNUYRAM-AWFVSMACSA-N 0.000 title 1
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 claims abstract description 22
- 239000002211 L-ascorbic acid Substances 0.000 claims abstract description 11
- 235000000069 L-ascorbic acid Nutrition 0.000 claims abstract description 11
- LHQIJBMDNUYRAM-DZSWIPIPSA-N L-erythro-biopterin Chemical compound N1=C(N)NC(=O)C2=NC([C@@H](O)[C@@H](O)C)=CN=C21 LHQIJBMDNUYRAM-DZSWIPIPSA-N 0.000 claims abstract description 11
- 229960005070 ascorbic acid Drugs 0.000 claims abstract description 11
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 claims abstract description 6
- 239000003513 alkali Substances 0.000 claims abstract description 3
- 239000002808 molecular sieve Substances 0.000 claims abstract 2
- URGAHOPLAPQHLN-UHFFFAOYSA-N sodium aluminosilicate Chemical compound [Na+].[Al+3].[O-][Si]([O-])=O.[O-][Si]([O-])=O URGAHOPLAPQHLN-UHFFFAOYSA-N 0.000 claims abstract 2
- 108010022394 Threonine synthase Proteins 0.000 claims description 7
- 102000004419 dihydrofolate reductase Human genes 0.000 claims description 7
- 238000004519 manufacturing process Methods 0.000 claims description 7
- 229960004617 sapropterin Drugs 0.000 claims description 6
- IOCJWNPYGRVHLN-MMALYQPHSA-N (2r)-2-amino-3-[[(2r)-2-amino-2-carboxyethyl]disulfanyl]propanoic acid;hydrochloride Chemical compound Cl.OC(=O)[C@@H](N)CSSC[C@H](N)C(O)=O IOCJWNPYGRVHLN-MMALYQPHSA-N 0.000 claims description 5
- FNKQXYHWGSIFBK-RPDRRWSUSA-N sapropterin Chemical compound N1=C(N)NC(=O)C2=C1NC[C@H]([C@@H](O)[C@@H](O)C)N2 FNKQXYHWGSIFBK-RPDRRWSUSA-N 0.000 claims description 3
- 239000003112 inhibitor Substances 0.000 claims description 2
- 102100022317 Dihydropteridine reductase Human genes 0.000 claims 1
- 101710088929 Voltage-dependent L-type calcium channel subunit alpha-1S Proteins 0.000 claims 1
- 239000003381 stabilizer Substances 0.000 abstract description 12
- 238000006243 chemical reaction Methods 0.000 abstract description 9
- 238000000034 method Methods 0.000 abstract description 8
- XUJNEKJLAYXESH-REOHCLBHSA-N L-Cysteine Chemical compound SC[C@H](N)C(O)=O XUJNEKJLAYXESH-REOHCLBHSA-N 0.000 abstract description 7
- 239000004201 L-cysteine Substances 0.000 abstract description 4
- 235000013878 L-cysteine Nutrition 0.000 abstract description 4
- OZRNSSUDZOLUSN-LBPRGKRZSA-N dihydrofolic acid Chemical compound N=1C=2C(=O)NC(N)=NC=2NCC=1CNC1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 OZRNSSUDZOLUSN-LBPRGKRZSA-N 0.000 abstract description 4
- 239000003638 chemical reducing agent Substances 0.000 abstract description 2
- 230000002255 enzymatic effect Effects 0.000 abstract description 2
- 230000002452 interceptive effect Effects 0.000 abstract 1
- 239000011541 reaction mixture Substances 0.000 abstract 1
- 239000000126 substance Substances 0.000 abstract 1
- 239000000243 solution Substances 0.000 description 11
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 11
- 239000012153 distilled water Substances 0.000 description 9
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 8
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 8
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 6
- 229920005654 Sephadex Polymers 0.000 description 6
- 239000012507 Sephadex™ Substances 0.000 description 6
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
- VFRROHXSMXFLSN-UHFFFAOYSA-N Glc6P Natural products OP(=O)(O)OCC(O)C(O)C(O)C(O)C=O VFRROHXSMXFLSN-UHFFFAOYSA-N 0.000 description 5
- NBSCHQHZLSJFNQ-GASJEMHNSA-N D-Glucose 6-phosphate Chemical compound OC1O[C@H](COP(O)(O)=O)[C@@H](O)[C@H](O)[C@H]1O NBSCHQHZLSJFNQ-GASJEMHNSA-N 0.000 description 4
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 4
- 229910052786 argon Inorganic materials 0.000 description 4
- OVBPIULPVIDEAO-LBPRGKRZSA-N folic acid Chemical compound C=1N=C2NC(N)=NC(=O)C2=NC=1CNC1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 OVBPIULPVIDEAO-LBPRGKRZSA-N 0.000 description 4
- 229940045189 glucose-6-phosphate Drugs 0.000 description 4
- 239000007788 liquid Substances 0.000 description 4
- 239000000203 mixture Substances 0.000 description 4
- 239000001301 oxygen Substances 0.000 description 4
- 229910052760 oxygen Inorganic materials 0.000 description 4
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 3
- 238000005406 washing Methods 0.000 description 3
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 2
- 102100024746 Dihydrofolate reductase Human genes 0.000 description 2
- -1 L-cysteine monosaccharide Chemical class 0.000 description 2
- OVBPIULPVIDEAO-UHFFFAOYSA-N N-Pteroyl-L-glutaminsaeure Natural products C=1N=C2NC(N)=NC(=O)C2=NC=1CNC1=CC=C(C(=O)NC(CCC(O)=O)C(O)=O)C=C1 OVBPIULPVIDEAO-UHFFFAOYSA-N 0.000 description 2
- ACFIXJIJDZMPPO-NNYOXOHSSA-N NADPH Chemical compound C1=CCC(C(=O)N)=CN1[C@H]1[C@H](O)[C@H](O)[C@@H](COP(O)(=O)OP(O)(=O)OC[C@@H]2[C@H]([C@@H](OP(O)(O)=O)[C@@H](O2)N2C3=NC=NC(N)=C3N=C2)O)O1 ACFIXJIJDZMPPO-NNYOXOHSSA-N 0.000 description 2
- 102000004316 Oxidoreductases Human genes 0.000 description 2
- 108090000854 Oxidoreductases Proteins 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 2
- UCTWMZQNUQWSLP-UHFFFAOYSA-N adrenaline Chemical compound CNCC(O)C1=CC=C(O)C(O)=C1 UCTWMZQNUQWSLP-UHFFFAOYSA-N 0.000 description 2
- 229960002433 cysteine Drugs 0.000 description 2
- 230000007812 deficiency Effects 0.000 description 2
- 238000011033 desalting Methods 0.000 description 2
- 108020001096 dihydrofolate reductase Proteins 0.000 description 2
- VYFYYTLLBUKUHU-UHFFFAOYSA-N dopamine Chemical compound NCCC1=CC=C(O)C(O)=C1 VYFYYTLLBUKUHU-UHFFFAOYSA-N 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 229960000304 folic acid Drugs 0.000 description 2
- 235000019152 folic acid Nutrition 0.000 description 2
- 239000011724 folic acid Substances 0.000 description 2
- 238000001727 in vivo Methods 0.000 description 2
- 239000000843 powder Substances 0.000 description 2
- 239000000047 product Substances 0.000 description 2
- QZAYGJVTTNCVMB-UHFFFAOYSA-N serotonin Chemical compound C1=C(O)C=C2C(CCN)=CNC2=C1 QZAYGJVTTNCVMB-UHFFFAOYSA-N 0.000 description 2
- SFLSHLFXELFNJZ-QMMMGPOBSA-N (-)-norepinephrine Chemical compound NC[C@H](O)C1=CC=C(O)C(O)=C1 SFLSHLFXELFNJZ-QMMMGPOBSA-N 0.000 description 1
- QIJRTFXNRTXDIP-UHFFFAOYSA-N (1-carboxy-2-sulfanylethyl)azanium;chloride;hydrate Chemical compound O.Cl.SCC(N)C(O)=O QIJRTFXNRTXDIP-UHFFFAOYSA-N 0.000 description 1
- BOEUHAUGJSOEDZ-UHFFFAOYSA-N 2-amino-5,6,7,8-tetrahydro-1h-pteridin-4-one Chemical class N1CCNC2=C1C(=O)N=C(N)N2 BOEUHAUGJSOEDZ-UHFFFAOYSA-N 0.000 description 1
- LEVONNIFUFSRKZ-UHFFFAOYSA-N 3-(carboxymethyl)-2,2-dimethylcyclobutane-1-carboxylic acid Chemical compound CC1(C)C(CC(O)=O)CC1C(O)=O LEVONNIFUFSRKZ-UHFFFAOYSA-N 0.000 description 1
- KYARBIJYVGJZLB-UHFFFAOYSA-N 7-amino-4-hydroxy-2-naphthalenesulfonic acid Chemical compound OC1=CC(S(O)(=O)=O)=CC2=CC(N)=CC=C21 KYARBIJYVGJZLB-UHFFFAOYSA-N 0.000 description 1
- 102000000632 Aromatic amino acid hydroxylases Human genes 0.000 description 1
- 108050008079 Aromatic amino acid hydroxylases Proteins 0.000 description 1
- 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 1
- 101100046352 Mus musculus Tjap1 gene Proteins 0.000 description 1
- 206010060860 Neurological symptom Diseases 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- 108010069013 Phenylalanine Hydroxylase Proteins 0.000 description 1
- 102100038223 Phenylalanine-4-hydroxylase Human genes 0.000 description 1
- 201000011252 Phenylketonuria Diseases 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 239000007853 buffer solution Substances 0.000 description 1
- 239000006227 byproduct Substances 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- 150000001721 carbon Chemical group 0.000 description 1
- 239000012295 chemical reaction liquid Substances 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 239000005515 coenzyme Substances 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 229960001305 cysteine hydrochloride Drugs 0.000 description 1
- 229960003638 dopamine Drugs 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 238000006911 enzymatic reaction Methods 0.000 description 1
- DUYAAUVXQSMXQP-UHFFFAOYSA-N ethanethioic S-acid Chemical compound CC(S)=O DUYAAUVXQSMXQP-UHFFFAOYSA-N 0.000 description 1
- 238000001640 fractional crystallisation Methods 0.000 description 1
- 238000004128 high performance liquid chromatography Methods 0.000 description 1
- 230000003211 malignant effect Effects 0.000 description 1
- 230000002503 metabolic effect Effects 0.000 description 1
- 239000002858 neurotransmitter agent Substances 0.000 description 1
- 229930027945 nicotinamide-adenine dinucleotide Natural products 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- SFLSHLFXELFNJZ-UHFFFAOYSA-N norepinephrine Natural products NCC(O)C1=CC=C(O)C(O)=C1 SFLSHLFXELFNJZ-UHFFFAOYSA-N 0.000 description 1
- 229960002748 norepinephrine Drugs 0.000 description 1
- 150000002926 oxygen Chemical class 0.000 description 1
- 229910052763 palladium Inorganic materials 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- 229910052697 platinum Inorganic materials 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 235000018102 proteins Nutrition 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 238000006722 reduction reaction Methods 0.000 description 1
- 229940076279 serotonin Drugs 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 238000001179 sorption measurement Methods 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 238000009423 ventilation Methods 0.000 description 1
Landscapes
- Preparation Of Compounds By Using Micro-Organisms (AREA)
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP19016082A JPS5982091A (ja) | 1982-10-29 | 1982-10-29 | バイオプテリンの製法 |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP19016082A JPS5982091A (ja) | 1982-10-29 | 1982-10-29 | バイオプテリンの製法 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPS5982091A true JPS5982091A (ja) | 1984-05-11 |
| JPH059065B2 JPH059065B2 (enrdf_load_stackoverflow) | 1993-02-03 |
Family
ID=16253418
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP19016082A Granted JPS5982091A (ja) | 1982-10-29 | 1982-10-29 | バイオプテリンの製法 |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPS5982091A (enrdf_load_stackoverflow) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4937342A (en) * | 1987-11-30 | 1990-06-26 | Kabushiki Kaisha Vitamin Kenkyusyo | Intermediates for synthesizing BH4 and its derivatives |
| JP2007511536A (ja) * | 2003-11-17 | 2007-05-10 | バイオマリン ファーマシューティカル インコーポレイテッド | 代謝障害の処置のための方法及び組成物 |
-
1982
- 1982-10-29 JP JP19016082A patent/JPS5982091A/ja active Granted
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4937342A (en) * | 1987-11-30 | 1990-06-26 | Kabushiki Kaisha Vitamin Kenkyusyo | Intermediates for synthesizing BH4 and its derivatives |
| JP2007511536A (ja) * | 2003-11-17 | 2007-05-10 | バイオマリン ファーマシューティカル インコーポレイテッド | 代謝障害の処置のための方法及び組成物 |
| US9993481B2 (en) | 2003-11-17 | 2018-06-12 | Biomarin Pharmaceutical Inc. | Methods and compositions for the treatment of metabolic disorders |
Also Published As
| Publication number | Publication date |
|---|---|
| JPH059065B2 (enrdf_load_stackoverflow) | 1993-02-03 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US5124452A (en) | Process for producing d,1-5-methyltetrahydrofolic acid and its salts | |
| JP2525965B2 (ja) | Ｎ５ −メチル−５，６，７，８−テトラヒドロ葉酸のアンモニウム塩およびその製造方法 | |
| JP2000136135A (ja) | 光学活性化合物を用いた組成物 | |
| JP2958902B2 (ja) | 三つの新規非ポリグルタマートのデアザアミノプテリンと合成方法 | |
| US5196533A (en) | Cyclization of 5 amino-pyrimidines to quinoid 6,6 disubstituted dihydropteridines | |
| JPH0149275B2 (enrdf_load_stackoverflow) | ||
| Bailey et al. | Synthesis of tetrahydropteridine C6-stereoisomers, including N5-formyl-(6S)-tetrahydrofolic acid | |
| IE46402B1 (en) | Process for the preparation of d, 1-5-methyltetra-hydrofolic acid | |
| WO1991013890A2 (fr) | Composes diastereoisomeres derivant de l'acide tetrahydrofolique, procede de preparation et utilisation dans la synthese de diastereoisomeres 6s et 6r de folates reduits | |
| JPS5982091A (ja) | バイオプテリンの製法 | |
| EP0138995B1 (en) | Regulation of enzymes which utilize tetrahydrobiopterin or tetrahydrofolate cofactors with 6, 6-disubstituted-tetrahydropteridines | |
| US5223500A (en) | Stable pharmaceutical composition of alkaline or alkaline earth 5-methyl tetrahydrofolate | |
| KR920007403B1 (ko) | L(-)-테트라히드로폴산의 제조방법 | |
| Bailey et al. | Changes in the cofactor binding domain of bovine striatal tyrosine hydroxylase at physiological pH upon cAMP-dependent phosphorylation mapped with tetrahydrobiopterin analogues | |
| WO2018153279A1 (en) | Dihydropyridophthalazinone compounds as inhibitors of poly (adp-ribose) polymerase (parp) for treatment of diseases and method of use thereof | |
| JP2674707B2 (ja) | Ｌ‐ビオプテリンの製法 | |
| Rosowsky et al. | Methotrexate analogs. 34. Replacement of the glutamate moiety in methotrexate and aminopterin by long-chain 2-aminoalkanedioic acids | |
| CN115124464B (zh) | 一种喹啉二酮磺酰哌嗪杂合体及其制备方法和应用 | |
| JPH05229948A (ja) | 悪性腫瘍の治療剤または診断剤およびａｃ８００７物質の製造法 | |
| CN112724200B (zh) | 一种稳定环孢霉素a的稀释液及其应用 | |
| KR20230023750A (ko) | 염소화 화합물의 제조 방법 | |
| JP4808853B2 (ja) | 新規抗腫瘍剤 | |
| GB1572138A (en) | Process for the preparation of d,1-5-methyltetrahydrofolic acid | |
| Waring et al. | The dihydropteridine reductase (human brain) activity of some lipophilic quinonoid dihydropterins | |
| EP0378706A1 (en) | 5-substituted uridine derivatives and intermediates for their preparation |