JP5599078B2 - アデノシンテトラホスフェート化合物の製造法 - Google Patents
アデノシンテトラホスフェート化合物の製造法 Download PDFInfo
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- JP5599078B2 JP5599078B2 JP2011519910A JP2011519910A JP5599078B2 JP 5599078 B2 JP5599078 B2 JP 5599078B2 JP 2011519910 A JP2011519910 A JP 2011519910A JP 2011519910 A JP2011519910 A JP 2011519910A JP 5599078 B2 JP5599078 B2 JP 5599078B2
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H19/00—Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof
- C07H19/02—Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof sharing nitrogen
- C07H19/04—Heterocyclic radicals containing only nitrogen atoms as ring hetero atom
- C07H19/16—Purine radicals
- C07H19/20—Purine radicals with the saccharide radical esterified by phosphoric or polyphosphoric acids
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
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Description
[1] 式(XI)化合物を縮合剤を用いて式(XIV)化合物に変換後(工程A)、マグネシウム、マンガンまたは鉄のいずれかより選択された金属塩の存在下、式(XIII)と反応させることにより式(I)化合物を得る(工程B)ことを特徴とするアデノシンテトラホスフェート化合物の製造法。
[5]金属塩がマグネシウム塩である、[1]に記載の製造法。
[6]工程Aと工程Bを連続して行う、[1]に記載の製造法。
式(II)化合物を、ルイス酸およびモレキュラーシーブスの存在下、フェノール化合物と反応させ、立体異性体混合物である式(III)化合物を得、得られた式(III)化合物から結晶化によりβ体(式(IV)化合物)のみを分離し、該化合物をアルカリ性条件下、脱保護して式(V)化合物を得る工程。
式(V)化合物の5位水酸基を選択的に保護し、2,3位水酸基を5位保護基とは除去法の異なる保護基で保護後、5位保護基を選択的に除去することにより、式(VII)化合物を得、該化合物を塩基の存在下、リン酸化して式(VIII)化合物とし、2,3位の保護基を除去して式(IX)化合物を得る工程。
式(IX)化合物のリン酸基を式(X)化合物に変換後、ピロリン酸塩と反応させることにより式(XI)化合物を得る工程。
(式中、Arはアリール基、Xは硫黄原子もしくは酸素原子またはイミノ基のいずれかより選ばれる基、R7はイミダゾリル基またはN−メチルイミダゾリル基、Mは水素原子またはイオンを示す。)
P1−[4−メトキシフェニルβ−D−リボフラノシド]5−]P4−(1−メチルアデノシン5’−)テトラリン酸(1)の合成
31P−NMR(D2O):δ−11.20(m),−23.00(m)
MS(ESI):m/z 838[M−H]−,860[M1Na−H]−,882[M2Na−H]−,905[M3Na−H]−,926[M4Na−H]−.
1)2,3、5−トリ−O−ベンゾイル−1−O−p−メトキシフェニル−β−D−リボ−ペントフラノース(9)の合成(方法1:化合物8を出発原料とする方法)
1−O−p−メトキシフェニル−β−D−リボ−ペントフラノース5−トリリン酸(5)の合成(方法2:N−メチルイミダゾリデート法)
1−メチルアデノシン5’−モノリン酸(12)の合成
エントリー1:
1−O−アセチル−β−D−リボ−ペントフラノース保護体としては、Rがアセチルの化合物2を使用し、公知文献(WO08/060632)に記載の方法に従って反応を行った。反応液を希釈した後、HPLCにより分析し、α、β立体異性体それぞれの存在比、α:β比を算出した。
1−O−アセチル−β−D−リボ−ペントフラノース保護体としては、Rがベンゾイルの化合物8を使用し、化合物8および4−メトキシフェノール(1.2当量)を有機溶媒(10mL/1gの化合物8)に溶解し、モレキュラーシーブス4A(Wako社、2g/1gの化合物8、または非存在下)を加え、室温で1時間撹拌した後、トリフルオロメタンスルホン酸トリメチルシリル(0.4mL/1gの化合物8)を加え、室温で24時間撹拌した。反応液を希釈後、HPLCにより分析し、エントリー1と同様にα:β比を算出した。
Claims (4)
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP2011519910A JP5599078B2 (ja) | 2009-06-23 | 2010-06-22 | アデノシンテトラホスフェート化合物の製造法 |
Applications Claiming Priority (4)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP2009148344 | 2009-06-23 | ||
JP2009148344 | 2009-06-23 | ||
PCT/JP2010/060577 WO2010150791A1 (ja) | 2009-06-23 | 2010-06-22 | アデノシンテトラホスフェート化合物の製造法 |
JP2011519910A JP5599078B2 (ja) | 2009-06-23 | 2010-06-22 | アデノシンテトラホスフェート化合物の製造法 |
Publications (2)
Publication Number | Publication Date |
---|---|
JPWO2010150791A1 JPWO2010150791A1 (ja) | 2012-12-10 |
JP5599078B2 true JP5599078B2 (ja) | 2014-10-01 |
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JP2011519910A Expired - Fee Related JP5599078B2 (ja) | 2009-06-23 | 2010-06-22 | アデノシンテトラホスフェート化合物の製造法 |
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JP (1) | JP5599078B2 (ja) |
WO (1) | WO2010150791A1 (ja) |
Families Citing this family (1)
Publication number | Priority date | Publication date | Assignee | Title |
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CN102659856A (zh) * | 2012-04-10 | 2012-09-12 | 常州康丽制药有限公司 | 1-O-乙酰基-2,3,5-三-O-苯甲酰基-β-D-呋喃核糖的制备工艺 |
Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2001510484A (ja) * | 1997-07-25 | 2001-07-31 | インスパイアー ファーマシューティカルズ,インコーポレイティド | ジ(ウリジン5’)−テトラホスフェート及びその塩の大規模生産のための方法 |
WO2008012949A1 (fr) * | 2006-07-26 | 2008-01-31 | Yamasa Corporation | Procédé servant à produire un di(nucléoside pyrimidique-5'-)polyphosphate |
WO2008060632A2 (en) * | 2006-11-17 | 2008-05-22 | Epix Delaware, Inc. | Adenosine analogs and their use |
Family Cites Families (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CA2714198A1 (en) * | 2008-02-15 | 2009-08-20 | Microdose Therapeutx, Inc. | Methods of making nucleoside tetraphosphate analogs |
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2010
- 2010-06-22 JP JP2011519910A patent/JP5599078B2/ja not_active Expired - Fee Related
- 2010-06-22 WO PCT/JP2010/060577 patent/WO2010150791A1/ja active Application Filing
Patent Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2001510484A (ja) * | 1997-07-25 | 2001-07-31 | インスパイアー ファーマシューティカルズ,インコーポレイティド | ジ(ウリジン5’)−テトラホスフェート及びその塩の大規模生産のための方法 |
WO2008012949A1 (fr) * | 2006-07-26 | 2008-01-31 | Yamasa Corporation | Procédé servant à produire un di(nucléoside pyrimidique-5'-)polyphosphate |
WO2008060632A2 (en) * | 2006-11-17 | 2008-05-22 | Epix Delaware, Inc. | Adenosine analogs and their use |
Non-Patent Citations (4)
Title |
---|
JPN6010049329; Qianwei Han et al.: 'One-Flask Synthesis of Dinucleoside Tetra- and Pentaphosphates' Org. Lett., 2006, 8 (10), p2075-2077 * |
JPN6010049330; PENDERGAST W. et al.: 'Synthesis and P2Y receptor activity of a series of uridine dinucleoside 5'-polyphosphates' BIOORG. MED. CHEM. LETT.,2001, 11(2),p157-160 * |
JPN6010049331; Hyojin Ko et al.: 'Synthesis and potency of novel uracil nucleotides and derivatives as P2Y2 and P2Y6 receptor agonists' Bioorganic & Medicinal Chemistry, 2008,16(12),p6319-6332 * |
JPN6010049332; Hiroaki Sawai et al.: 'Mg(II) ion-mediated conversion of mono- and oligonucleotides to 5'-polyphosphates in aqueous soluti' Tetrahedron Letters,1993, 34(30),p4801-4804 * |
Also Published As
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JPWO2010150791A1 (ja) | 2012-12-10 |
WO2010150791A1 (ja) | 2010-12-29 |
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