JPH01320993A - Production of l-biopterin - Google Patents
Production of l-biopterinInfo
- Publication number
- JPH01320993A JPH01320993A JP15221788A JP15221788A JPH01320993A JP H01320993 A JPH01320993 A JP H01320993A JP 15221788 A JP15221788 A JP 15221788A JP 15221788 A JP15221788 A JP 15221788A JP H01320993 A JPH01320993 A JP H01320993A
- Authority
- JP
- Japan
- Prior art keywords
- biopterin
- hydroxy
- pteridine
- oxopropyl
- amino
- 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
- 238000004519 manufacturing process Methods 0.000 title claims description 5
- 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 claims abstract description 9
- 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 9
- 102000004222 Sepiapterin reductase Human genes 0.000 claims abstract description 5
- 108020001302 Sepiapterin reductase Proteins 0.000 claims abstract description 5
- BFZQVTVNJYVVMH-UHFFFAOYSA-N 2-amino-6-(1-hydroxy-2-oxopropyl)-1h-pteridin-4-one Chemical compound N1C(N)=NC(=O)C2=NC(C(O)C(=O)C)=CN=C21 BFZQVTVNJYVVMH-UHFFFAOYSA-N 0.000 claims abstract description 4
- 230000015572 biosynthetic process Effects 0.000 abstract description 8
- 238000000034 method Methods 0.000 abstract description 8
- 239000003814 drug Substances 0.000 abstract description 4
- 102000000632 Aromatic amino acid hydroxylases Human genes 0.000 abstract description 3
- 108050008079 Aromatic amino acid hydroxylases Proteins 0.000 abstract description 3
- 239000005515 coenzyme Substances 0.000 abstract description 3
- 230000000694 effects Effects 0.000 abstract description 3
- 239000002994 raw material Substances 0.000 abstract description 3
- 239000007858 starting material Substances 0.000 abstract description 3
- 239000002243 precursor Substances 0.000 abstract description 2
- 229940079593 drug Drugs 0.000 abstract 1
- 230000002255 enzymatic effect Effects 0.000 abstract 1
- 230000000707 stereoselective effect Effects 0.000 abstract 1
- 238000003786 synthesis reaction Methods 0.000 description 6
- 239000000126 substance Substances 0.000 description 4
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- 150000001875 compounds Chemical class 0.000 description 3
- CPNGPNLZQNNVQM-UHFFFAOYSA-N pteridine Chemical compound N1=CN=CC2=NC=CN=C21 CPNGPNLZQNNVQM-UHFFFAOYSA-N 0.000 description 3
- UCTWMZQNUQWSLP-UHFFFAOYSA-N adrenaline Chemical compound CNCC(O)C1=CC=C(O)C(O)=C1 UCTWMZQNUQWSLP-UHFFFAOYSA-N 0.000 description 2
- 239000012153 distilled water Substances 0.000 description 2
- VYFYYTLLBUKUHU-UHFFFAOYSA-N dopamine Chemical compound NCCC1=CC=C(O)C(O)=C1 VYFYYTLLBUKUHU-UHFFFAOYSA-N 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-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
- 206010003805 Autism Diseases 0.000 description 1
- 208000020706 Autistic disease Diseases 0.000 description 1
- 206010012289 Dementia Diseases 0.000 description 1
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 1
- YJPIGAIKUZMOQA-UHFFFAOYSA-N Melatonin Natural products COC1=CC=C2N(C(C)=O)C=C(CCN)C2=C1 YJPIGAIKUZMOQA-UHFFFAOYSA-N 0.000 description 1
- XJLXINKUBYWONI-NNYOXOHSSA-N NADP zwitterion Chemical compound NC(=O)C1=CC=C[N+]([C@H]2[C@@H]([C@H](O)[C@@H](COP([O-])(=O)OP(O)(=O)OC[C@@H]3[C@H]([C@@H](OP(O)(O)=O)[C@@H](O3)N3C4=NC=NC(N)=C4N=C3)O)O2)O)=C1 XJLXINKUBYWONI-NNYOXOHSSA-N 0.000 description 1
- 208000012902 Nervous system disease Diseases 0.000 description 1
- 208000025966 Neurological disease Diseases 0.000 description 1
- 208000018737 Parkinson disease Diseases 0.000 description 1
- 230000007812 deficiency Effects 0.000 description 1
- 238000010586 diagram Methods 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 229960003638 dopamine Drugs 0.000 description 1
- 238000006911 enzymatic reaction Methods 0.000 description 1
- 210000003743 erythrocyte Anatomy 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 238000004128 high performance liquid chromatography Methods 0.000 description 1
- 238000009776 industrial production Methods 0.000 description 1
- 239000000543 intermediate Substances 0.000 description 1
- 210000003127 knee Anatomy 0.000 description 1
- 230000003211 malignant effect Effects 0.000 description 1
- 229960003987 melatonin Drugs 0.000 description 1
- DRLFMBDRBRZALE-UHFFFAOYSA-N melatonin Chemical compound COC1=CC=C2NC=C(CCNC(C)=O)C2=C1 DRLFMBDRBRZALE-UHFFFAOYSA-N 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 229960002748 norepinephrine Drugs 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
- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 230000003595 spectral effect Effects 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 235000000346 sugar Nutrition 0.000 description 1
- 150000008163 sugars Chemical class 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 238000001308 synthesis method Methods 0.000 description 1
- 238000010189 synthetic method Methods 0.000 description 1
- 238000000108 ultra-filtration Methods 0.000 description 1
Landscapes
- Preparation Of Compounds By Using Micro-Organisms (AREA)
Abstract
Description
【発明の詳細な説明】
（産業上の利用分野）
本発明はＬ−ビオプテリンの製法に係り、殊に酵素法に
よる製法に係る。DETAILED DESCRIPTION OF THE INVENTION (Industrial Application Field) The present invention relates to a method for producing L-biopterin, and particularly to a method for producing L-biopterin using an enzymatic method.
本発明方法により得られる し−ビオプテリンは、芳香
族アミノ酸水酸化酵素の補酵素であり且つ医薬としても
有用な５．６，７．８−テトラヒドロ−し−エリスロー
ビオプテリン（以下、ｒＢＨ４Ｊと略記する）やその関
連物質を合成するための前駆体として用いることができ
る。Shi-biopterin obtained by the method of the present invention is a coenzyme of aromatic amino acid hydroxylase and is also useful as a medicine. ) and its related substances can be used as precursors to synthesize them.
（従来の技術）
Ｂ１１４は芳香族アミノ酸水酸化酵素の補酵素であり、
従ってドーパミン、ノルアドレナリン、アドレナリン、
メラトニンの生合成に必須の化合物であり、式
にて示される構造を有している。(Prior art) B114 is a coenzyme of aromatic amino acid hydroxylase,
Therefore, dopamine, noradrenaline, adrenaline,
It is an essential compound for the biosynthesis of melatonin, and has the structure shown by the formula.
このＢ１（４が欠乏すると、悪性高フェニルアラニン血
症、パーキンソン病等の重篤な神経症が発症することが
判明しており、最近に至りこれら疾患による症状がＢ１
０の投与により著しく改善されることが判明している。It has been found that a deficiency of B1 (4) causes serious neurological disorders such as malignant hyperphenylalaninemia and Parkinson's disease, and recently the symptoms of these diseases have been
It has been found that administration of 0 provides significant improvement.
更に、■４は小児自閉症や智病の治療にも有効であると
されている。Furthermore, ■4 is said to be effective in treating childhood autism and dementia.
このように、有用な薬理学的性質を有しているために、
Ｂ１０の合成に関しては従来から種々の研究がなされて
きた［例えばＥ、 Ｌ、 ＰｉｔＬｅｒｓｏｎ等”Ｊ、
Ａｍ、 Ｃｈｅｗ、 Ｓｏｃ、” 第７８ ｌｂ、第
５８６８頁（１９５６年）、■、 Ｒｅｍｂｏｌｄ等“
Ｃｈｅｗ、 Ｈｅｒ、”第９６巻、第１３９５頁（１９
６３年）、Ｅ、 Ｃ，Ｔａｙｌｏｒ等“Ｊ、＾ｔｓ、
Ｃｈｅｗ、 Ｓｏｃ、”第９８巻、第２３０１頁（１９
７６年）、Ｍ、 ＶｉｓｃｏａＬｉｏｉ等”Ｈｅ１ｖ、
ＣｈｉＩｌ。Thus, due to its useful pharmacological properties,
Various studies have been conducted regarding the synthesis of B10 [for example, E. L., PitLerson et al., J.
Am, Chew, Soc,” No. 78 lb, p. 5868 (1956), ■, Rembold et al.
Chew, Her, vol. 96, p. 1395 (19
63), E. C. Taylor et al. “J.^ts.
Chew, Soc, vol. 98, p. 2301 (19
1976), M. ViscoaLioi et al.”He1v,
ChiIl.
Ａｃ ｔａ″第５２巻、第１２２５頁（１９６９年）、
同５５巻、第５７４頁（１９７２年）、同６０巻、第２
１１頁（１９７７年）、同６２巻、第２５７７頁（１９
７９年）、Ｋ、 Ｊ、 Ｍ、 ｊａｄｒｅｗｓ等″Ｊ、
Ｃｈｅ＋＊。Acta'' Volume 52, Page 1225 (1969),
Vol. 55, p. 574 (1972), Vol. 60, No. 2
11 (1977), Vol. 62, No. 2577 (1977)
79), K., J., M., Jadrews et al.''J.
Che+*.
Ｓｏｃ、 ” （ｅ）第９２８頁（１９６９年）、Ｓ、
Ｍａｔｓａａｒａ等″Ｂｕ１１． Ｃｈｅｗ、 Ｓｏ
ｃ、Ｊｐｎ、”第４８巻、第３７６７頁（１９７５年）
、同５２巻、第１８１頁（１９７９年）、”Ｃｈｅｗ、
Ｌｅｔｔ、”第７３５頁（１９８４年）、特開昭５９
−２１６８５、同５９−８２０９１、同６０−２０４７
８６等１゜（発明が解決しようとする課題）
従来提案されてきた１１１１．の合成法は、側鎖の不斉
源として、何れも高価な糖を出発原料としている点に先
ず問題があり、更に合成に多段階を要し、不安定な中間
体を経由し、又反応処理が煩雑であるために、収率や純
度の低下を招き、然かも精製が面倒であり、従って工業
的製造に適用し難いのが実情であった。Soc,” (e) p. 928 (1969), S.
Matsaara et al.''Bu11. Chew, So
c, Jpn, vol. 48, p. 3767 (1975)
, vol. 52, p. 181 (1979), “Chew.
Lett,” p. 735 (1984), Japanese Patent Application Publication No. 1983.
-21685, 59-82091, 60-2047
86 etc. 1° (Problem to be solved by the invention) 1111. The first problem with these synthetic methods is that they all use expensive sugars as starting materials as a source of chiral side chains.Additionally, the synthesis requires multiple steps, involves unstable intermediates, and The complicated process leads to a decrease in yield and purity, and furthermore, purification is troublesome, so it is difficult to apply it to industrial production.
（課題を解決するための手段及び作用）本発明者等は、
ＢＨ，の実用的な合成法を開発するために、出発原料が
廉価なこと、合成工程数が少ないこと、収率が良好なこ
と、出来得ればＢ１１４のみならず関連物質、即ち８■
４類縁体の合成にも適用可能なこと等を考慮して研究を
重ねた結果、８１（、及びその関連物質の合成用原料と
して有用なし一ビオプテリンが２−アミノ−４−ヒドロ
キシ−６−（１’−ヒドロキシ−２°−オキソプロピル
）プテリジンにセピアプテリン還元酵素を作用させるこ
とにより容易に且つ有利に得られることを見い出し、本
発明を完成するに至った。即ち、２−アミノ−４−ヒド
ロキシ−６−（１’−ヒドロキシ−２°−オキソプロピ
ル）プテリジンを還元処理する場合に生成する化合物と
しては、下記の工程図に示されるように、４種類の化合
物が考えられるが、本発明方法によれば、目的とするＬ
−ビオプテリン（化Ｃす
（実施例）
次に、実施例により本発明を更に詳細に且つ具体的に説
明する。(Means and effects for solving the problem) The present inventors,
In order to develop a practical synthesis method for BH, we need inexpensive starting materials, a small number of synthesis steps, a good yield, and if possible, not only B114 but also related substances, i.e. 8
As a result of repeated research, taking into consideration that it could be applied to the synthesis of 4 analogs, we found that biopterin is not useful as a raw material for the synthesis of 81 (and its related substances). The present inventors have discovered that 2-amino-4-pteridine can be easily and advantageously obtained by treating sepiapterin reductase with 1'-hydroxy-2°-oxopropyl) pteridine, and have completed the present invention. As shown in the process diagram below, four types of compounds are considered to be generated when hydroxy-6-(1'-hydroxy-2°-oxopropyl)pteridine is reduced, but the present invention According to the method, the target L
-Biopterin (chemical compound) (Examples) Next, the present invention will be explained in more detail and specifically with reference to Examples.
及１匠
２−アミノ−４−ヒドロキシ−６−（１’−ヒドロキシ
−２゛−オキソプロピル）プテリジン２３．６＋ａｇ
（１００μｍｏｌ）を蒸留水１００１中に溶解させ、０
．２Ｍ燐酸緩衝液（ｐＨ６，４） １００ｍ１に溶解さ
せたβ−ニコチンアミドアデニンジヌクレオチド燐酸（
還元型） １６７ｍｇを上記の溶液に添加した。更に、
ラット赤血球由来のものであって、末岡等の方法１″Ｂ
ｉｏｃｈｉｍ、 Ｂｉｏｐｈｙｓ、 Ａｃｔａ”第７１
７巻、第２６５頁（１９８２年）ｌにより部分精製した
セピアプテリン還元酵素を ｌ単位旦添加し、得られた
溶液を３０°Ｃで５時間、振盪しながらインキュベート
し、次いで限外濾過膜により濾過した後に、凍結乾燥さ
せた。この凍結乾燥物を６０１の０．１Ｎ Ｗ）’ａ／
ＭｅＯＨ混液（９５１５，ｖ／ｖ）に溶解させ、デベロ
シルＯＤＳカラムを用い高速液体クロマトグラフィーに
より精製した。得られた し−ビオプテリン含有画分か
ら溶媒を留去させた後に、残留物を少量の蒸留水に懸濁
させ、凍結乾燥することにより、所望のし一ビオプテリ
ンを淡黄色粉末として１０．５１１＋ｇ得た（収率：４
４％）。and 1 Takumi 2-amino-4-hydroxy-6-(1'-hydroxy-2'-oxopropyl) pteridine 23.6+ag
(100 μmol) was dissolved in distilled water 1001, and 0
．． β-nicotinamide adenine dinucleotide phosphate (
167 mg of the reduced form) was added to the above solution. Furthermore,
It is derived from rat red blood cells and is carried out by Sueoka et al.'s method 1''B.
iochim, Biophys, Acta” No. 71
7, p. 265 (1982), one unit of sepiapterin reductase was added once, the resulting solution was incubated with shaking at 30°C for 5 hours, and then passed through an ultrafiltration membrane. After filtration, it was freeze-dried. This freeze-dried product was heated to 0.1 N of 601 W)'a/
It was dissolved in a MeOH mixture (9515, v/v) and purified by high performance liquid chromatography using a Deverosil ODS column. After distilling off the solvent from the obtained shi-biopterin-containing fraction, the residue was suspended in a small amount of distilled water and lyophilized to obtain 10.511+ g of the desired shi-biopterin as a pale yellow powder. (Yield: 4
4%).
［αｌ；’ ニー６０°（ｃ ＝ ０．１３．０．１Ｎ
ＩＩｃＩ）ｕｖスペクトル（０，ＩＮ １１ＣＩ）λ
Ｆ、ｌＸ ＋１１＋１ ：２１０，２４７，３２０
’ＩＩ−ＮＭＲスヘクトル（ＤＭＳＯ−０６） ８ Ｐ
Ｐ１ｌ ：！、０６ Ｄ）Ｉ、 ｄ、 Ｊ ＝
６Ｈｚ、 −ＣＩ＋３）３．９２ （ＩＨ，ｍ、
２′−Ｈ）４．４４ （ＩＨ，ｄｄ、 Ｊ ＝
５Ｈｚ、 ５１１ｚ、 １″−Ｉ＋）４．６９
（ＩＨ，ｄ、 Ｊ ＝ ５Ｈｚ、 ２’−０■
）５．５８ （Ｉｌｌ、ｄ、 Ｊ ：５Ｈｚ、
ｌ’−０Ｈ）６．８６ （２１１，ｓ 、 ２−
Ｎｌｈ）８、月 （１■、 ｓ、 ？−Ｈ）
１１．４２ ＜ＩＨ，ｂｒ、ｓ、３−ＮＨ）尚、上記
の比旋光度値はＢ、 Ｇｒｅｅｎ等の報告［”Ｃｈｅｗ
、 Ｈｅｒ、”第９９巻、第２１６２頁（１９６６年）
１における値と略一致するものであり、ｕｖ及びＮＭＲ
スペクトル値は標品における値と一致するものである。[αl;' Knee 60° (c = 0.13.0.1N
IIcI) uv spectrum (0, IN 11CI) λ
F, lX +11+1:210,247,320'II-NMR spectrum (DMSO-06) 8 P
P1l:! , 06 D) I, d, J =
6Hz, -CI+3)3.92 (IH,m,
2'-H) 4.44 (IH, dd, J =
5Hz, 511z, 1″-I+)4.69
(IH, d, J = 5Hz, 2'-0■
)5.58 (Ill, d, J: 5Hz,
l'-0H)6.86 (211,s, 2-
Nlh) 8, Moon (1■, s, ?-H) 11.42 <IH, br, s, 3-NH) The above specific optical rotation value is based on the report by B, Green et al. ["Chew
, Her,” Vol. 99, p. 2162 (1966)
1, which is approximately the same as the value in UV and NMR
The spectral values match those in the standard specimen.
（発明の効果）
本発明方法によれば、２−アミノ−４−ヒドロキシ−６
−（１’−ヒドロキシ−２゛−オキソプロピル）プテリ
ジンから出発し″ＣＬＣビープテリンを容易に且つ立体
特異的に得ることができる。(Effect of the invention) According to the method of the invention, 2-amino-4-hydroxy-6
Starting from -(1'-hydroxy-2'-oxopropyl)pteridine, CLC beepterin can be easily and stereospecifically obtained.
本発明方法により得られる し−ビオプテリンは医薬と
して有用なりｉｔ４やその関連物質合成用の原料として
用いることができるので、本発明はこれら医薬品の製造
コストの低廉化を可能にするものである。Since the biopterin obtained by the method of the present invention is useful as a medicine and can be used as a raw material for the synthesis of IT4 and related substances, the present invention makes it possible to reduce the manufacturing cost of these pharmaceuticals.
Claims (1)
ロキシ−２′−オキソプロピル）プテリジンにセピアプ
テリン還元酵素を作用させることを特徴とする、Ｌ−ビ
オプテリンの製法。(1) A method for producing L-biopterin, which comprises reacting 2-amino-4-hydroxy-6-(1'-hydroxy-2'-oxopropyl)pteridine with sepiapterin reductase.
Priority Applications (7)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP15221788A JP2674707B2 (en) | 1988-06-22 | 1988-06-22 | L-Biopterin manufacturing method |
| DE3853711T DE3853711T2 (en) | 1987-11-30 | 1988-11-29 | Intermediates for the synthesis of 5,6,7,8-tetrahydro-L-erythro-biopterin and its derivatives. |
| EP88119891A EP0318926B1 (en) | 1987-11-30 | 1988-11-29 | Intermediates for synthesizing 5,6,7,8-tetrahydro-L-erythro-biopterin and its derivatives |
| US07/277,109 US4937342A (en) | 1987-11-30 | 1988-11-29 | Intermediates for synthesizing BH4 and its derivatives |
| CA000584504A CA1334654C (en) | 1987-11-30 | 1988-11-29 | Intermediates for synthesizing bh _and its derivatives |
| US07/515,962 US5037981A (en) | 1987-11-30 | 1990-04-27 | Intermediates for synthesizing BH4 and its derivatives |
| CA000616950A CA1338149C (en) | 1987-11-30 | 1994-12-13 | Intermediates for synthesizing bh- and its derivatives |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP15221788A JP2674707B2 (en) | 1988-06-22 | 1988-06-22 | L-Biopterin manufacturing method |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPH01320993A true JPH01320993A (en) | 1989-12-27 |
| JP2674707B2 JP2674707B2 (en) | 1997-11-12 |
Family
ID=15535637
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP15221788A Expired - Lifetime JP2674707B2 (en) | 1987-11-30 | 1988-06-22 | L-Biopterin manufacturing method |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JP2674707B2 (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPWO2002018587A1 (en) * | 2000-08-31 | 2004-01-15 | 第一サントリーファーマ株式会社 | Method for producing biopterins |
Families Citing this family (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US7361759B2 (en) | 2004-12-27 | 2008-04-22 | Shiratori Pharmaceutical Co., Ltd | Method for producing L-biopterin |
| TW200942542A (en) | 2008-01-07 | 2009-10-16 | Biomarin Pharm Inc | Method of synthesizing tetrahydrobiopterin |
-
1988
- 1988-06-22 JP JP15221788A patent/JP2674707B2/en not_active Expired - Lifetime
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPWO2002018587A1 (en) * | 2000-08-31 | 2004-01-15 | 第一サントリーファーマ株式会社 | Method for producing biopterins |
| JP4817590B2 (en) * | 2000-08-31 | 2011-11-16 | 第一三共株式会社 | Method for producing biopterins |
Also Published As
| Publication number | Publication date |
|---|---|
| JP2674707B2 (en) | 1997-11-12 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US20230023607A1 (en) | Methods for practical synthesis of deuterated amino acids | |
| US4649197A (en) | Sulfate of 5,6,7,8-tetrahydro-L-erythro-biopterin and process for preparing the same | |
| JP7028780B2 (en) | Benzamide derivative | |
| RU94046317A (en) | New synthetic intermediate compound for preparing amino acid derivatives and processes for preparing amino acid derivatives | |
| JPH01320993A (en) | Production of l-biopterin | |
| CN109776554B (en) | Dihydrochromone spliced pyrrole spiro-oxoindole compound and preparation method and application thereof | |
| JPS60204786A (en) | Synthesis of (6r)-tetrahydrobiopterin and its relating substance | |
| JPH08502752A (en) | Novel substituted azetidinones as anti-inflammatory and anti-modifying agents | |
| CN108276420B (en) | 8, 13-dihydrobenzo [5,6] chromene [2,3-b ] indole compound and synthetic method thereof | |
| EP0634995B1 (en) | Process and intermediate for the purification of oxytetracycline | |
| MXPA06002145A (en) | Cycloalkylaminoacid compounds, processes for making and uses thereof. | |
| JPS61172877A (en) | Production of (6r)-tetrahydro-l-biopterin | |
| CN112939852B (en) | Resolution method of aromatic cyclopropane derivative racemic isomer | |
| CN109369672B (en) | Preparation method of polysubstituted cycloheptatriene derivative | |
| JPS62242692A (en) | Production of moranoline derivative | |
| CN114907228B (en) | Colchicine and magnolol compound, synthesis method thereof and application thereof in resisting new coronaviruses | |
| CN113735873B (en) | Method for preparing Artemisinin G | |
| JP2611790B2 (en) | Tetrahydrofuranyl pyrimidine derivative | |
| Cowart et al. | A new synthesis of double labeled [7, 9‐13C2] folic acid | |
| JPH03264558A (en) | 2'-ketopantothenonitrile | |
| JPH02111747A (en) | Preparation of carbon 13-marked 5-aminolevulinic acid and derivative thereof | |
| Zhang et al. | Synthesis of [(3 S, 5 R)-3-Hydroxy-5-methylpiperidin-1-yl](2-methylpyridin-3-yl) methanone | |
| JPH01252295A (en) | Production of 2,3-dicyano-5,6-dicyanopurazine | |
| JPH01143873A (en) | Pteridine derivative | |
| JPS6054361A (en) | Production of indole derivative |