JPWO2010079579A1 - ハロゲン置換糖類、その製造方法、その反応組成物及びその製造装置 - Google Patents
ハロゲン置換糖類、その製造方法、その反応組成物及びその製造装置 Download PDFInfo
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- JPWO2010079579A1 JPWO2010079579A1 JP2010545645A JP2010545645A JPWO2010079579A1 JP WO2010079579 A1 JPWO2010079579 A1 JP WO2010079579A1 JP 2010545645 A JP2010545645 A JP 2010545645A JP 2010545645 A JP2010545645 A JP 2010545645A JP WO2010079579 A1 JPWO2010079579 A1 JP WO2010079579A1
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- C—CHEMISTRY; METALLURGY
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- C07H5/00—Compounds containing saccharide radicals in which the hetero bonds to oxygen have been replaced by the same number of hetero bonds to halogen, nitrogen, sulfur, selenium, or tellurium
- C07H5/02—Compounds containing saccharide radicals in which the hetero bonds to oxygen have been replaced by the same number of hetero bonds to halogen, nitrogen, sulfur, selenium, or tellurium to halogen
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- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K51/00—Preparations containing radioactive substances for use in therapy or testing in vivo
- A61K51/02—Preparations containing radioactive substances for use in therapy or testing in vivo characterised by the carrier, i.e. characterised by the agent or material covalently linked or complexing the radioactive nucleus
- A61K51/04—Organic compounds
- A61K51/0491—Sugars, nucleosides, nucleotides, oligonucleotides, nucleic acids, e.g. DNA, RNA, nucleic acid aptamers
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- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
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Abstract
Description
本発明は、化1又は化2の脱離基置換糖類から、化4又は化5のハロゲン置換糖類を、一段階の反応プロセスで、触媒無添加、短時間の反応条件下で、選択的かつ連続的に合成することを特徴とするものである。本発明では、上記反応溶媒として、高温高圧水、又は温度100〜400℃、圧力0.1〜40MPaの亜臨界流体、又は超臨界流体が用いられ、好適には亜臨界水が用いられる。また、反応条件として、好適には、温度200℃、圧力5MPa、反応時間は3〜180秒の範囲、好適には反応時間が10秒程度に調整される。
(1)脱離基置換糖類から、高速で、連続的に、ハロゲン置換糖類を合成することができる。
(2)ハロゲン置換糖類を、廃棄物量を低減しつつ、高効率で選択的に合成することができる。
(3)触媒及び非プロトン性有機溶媒を用いない合成プロセスを実現できる。
(4)そのため、触媒及び非プロトン性有機溶媒の残存がなく、生態系に対して有害性がなく、生体に対して安全性の高いハロゲン置換糖類組成物を提供できる。
(5)生成物が水に溶解しない場合には、排出された固液分散水溶液に対して更に水を注入することで、洗浄しつつ固液二層に分液し、高純度の生成物を容易に回収できる。
(6)医薬品として有用なハロゲン置換糖類の新しい大量生産プロセスとして、既存の生産プロセスに代替し得る新しい生産技術を提供できる。
(7)ポジトロン放射断層撮影(PET)における放射核種であるトレーサー(寿命数分)のハロゲン置換糖類組成物を寿命以内に少量かつ高速で生産可能な簡易製造技術及びコンパクトな製造装置を提供できる。
(8)トレーサー合成に関与する化合物が低減されるため、放射能汚染廃棄物を更に低減することができる。
(実施方法)
まず、本発明の実施方法を示した後、実施例を示す。以下の実施例では、図9の流通式高温高圧反応装置を用いて、合成条件を、無触媒、温度150〜300℃、圧力5〜10MPa、滞留時間3〜180秒で本発明を実施した。図9の流通式高温高圧反応装置の本体(主要部分)を、図7の流通型高温高圧流体その場赤外分光測定装置に設置した装置にて、まず、所定温度、所定圧力に設定し、ポンプ5により、純水を、流量5.0ml/minで、窓なしセル(ティー1)へ送液した。
2 φ4mm×5.0mmL六角ネジ
3 ワンリングフェラル付オネジ
4 SUS316チューブ
5 水送液ポンプ
6 反応物送液ポンプ
7 洗浄水送液ポンプ
8 冷却フランジ(冷却水が循環する)
9 水加熱コイル
10 反応物導入管
11 温度センサー
12 温度センサーシース
13 炉体
14 高温高圧フローセル
15 ZnSe窓
16 溶媒導入管
17 排出配管
18 ティー
19 背圧弁
21 水溶液
22 洗浄水
23 水溶液ポンプ
24 洗浄用純水送液ポンプ
25 炉体加熱システム
26 炉体
27 高温高圧赤外フローセル
28 冷却水(入口)
29 冷却水(出口)
30 背圧弁
31 排出水溶液受器
32 可動鏡
33 可動鏡
34 干渉計
35 光源
36 赤外レーザー
37 MCT受光器
38 TGS受光器
39 解析モニター
40 反応物送液ポンプ
41 基質送液ポンプ
42 水送液ポンプ
43 反応ティー
44 配管
45 混合ティー
46 排出配管
47 冷却器
48 背圧弁
49 回収容器
50 温度センサー
51 温度センサー
Claims (9)
- ハロゲン置換糖類合成反応により、脱離基置換保護化糖類又は脱離基置換糖類とハロゲン化塩とから合成される、ハロゲン置換反応物を含有する又はポジトロン放射断層撮影(PET)におけるトレーサー用ハロゲン置換糖類を含有するヒト及び生体に有害な触媒及び非プロトン性有機溶媒の残存がないことを特徴とするハロゲン置換糖類水溶液。
- ハロゲン置換糖類を合成する方法において、高温高圧状態の亜臨界流体ないしは超臨界流体を反応溶媒として使用することで、脱離基置換保護化糖類とハロゲン化塩とから、溶媒置換することなく、無触媒で、ハロゲン置換及び脱保護を一段階で行い、ハロゲン置換糖類を選択的に合成することを特徴とするハロゲン置換糖類の製造方法。
- ハロゲン置換糖類を合成する方法において、高温高圧状態の亜臨界流体ないしは超臨界流体を反応溶媒として使用することで、脱離基置換糖類とハロゲン化塩とから、溶媒置換することなく、無触媒で、ハロゲン置換を一段階で行い、ハロゲン置換糖類を選択的に合成することを特徴とするハロゲン置換糖類の製造方法。
- 温度100〜400℃、圧力0.1〜40MPaの亜臨界流体ないし超臨界流体を反応溶媒として使用する、請求項2又は3に記載の方法。
- 亜臨界流体ないし超臨界流体として、水、エタノール、それ以外の無機溶媒、もしくは有機溶媒もしくは無機溶媒と有機溶媒の混合溶媒を用いる、請求項2又は3に記載の方法。
- 流通式高温高圧装置に、基質及び反応溶媒を導入し、反応時間を3〜180秒の範囲で変化させることで合成反応を実施する、請求項2又は3に記載の方法。
- ハロゲン置換糖類を合成する方法において、炭酸水素ナトリウム(重曹)のヒト及び生体に無害な添加物を添加して合成反応を加速する、請求項2又は3に記載の方法。
- 流路空間がマイクロ空間であるマイクロ反応システムであって、水を送液する水送液ポンプ、水加熱用コイル、高温高圧フローセル、基質を送液する反応物送液ポンプ、炉体、反応物を炉体に導入する反応物導入管、反応溶液を排出する排出液ライン、冷却フランジ及び圧力を設定する背圧弁を具備し、上記高温高圧フローセルで、高温高圧水のフローに対して脱離基置換保護化糖類とハロゲン塩を溶解した水溶液フロー又は脱離基置換糖類とハロゲン塩を溶解した水溶液フローを直角に衝突させ、ハロゲン置換糖類を選択的に合成するようにしたことを特徴とするハロゲン置換糖類合成装置。
- ハロゲン置換糖類合成後、回収水溶液に水を注入してデカンテーションし、固液二層溶液に分離後、ハロゲン置換糖類を含む固体を1回の操作で分離回収することを特徴とする、該ハロゲン置換糖類を含む固体の簡易な固液連続分離法。
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