| Project/Area Number |
17K05827
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Functional solid state chemistry
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| Research Institution | Chiba University |
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Principal Investigator |
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| Project Period (FY) |
2017-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2019: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2017: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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| Keywords | 包接結晶 / 光学分割 / アミノ酸誘導体 / 水素結合 / 結晶化誘起動的分割 / 結晶化誘起動的光学分割 / 結晶工学 / 合成化学 / 有機工業化学 |
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| Outline of Final Research Achievements |
We developed two major projects. (1) We developed two kinds of chiral urea hosts having bulky groups such as Host-1 (4-tritylphenyl group) and Host 2 (methoxydiphenylpropyl group) derived from alanine. Under basic conditions, crystallization-induced dynamic resolution (CIDR) of racemic 2-phenylpropaneamide by Host 1 proceeded to give the (S)-form with 96% ee. In addition, Host-2 included (S)-2-chlorobutanamide with good selectivity of 60% ee. This system will be expected to apply the CIDR using Finkelstein reaction.
(2) We investigated the diastereomeric separation of 3-cyanocycloalkanones by fractional crystallization after ketalization of these racemic cycloalkanones with the chiral 1,2-diphenylethane-1,2-diol. Since the nitriles were not crystallized, we transformed them to the corresponding amides and achieved fractional crystallization with high diastereoselectivity (99% de). We also found crystallization-induced diastereomer transformation using potassium butoxide as a base.
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| Academic Significance and Societal Importance of the Research Achievements |
医薬品の多くは光学活性体であり，キラルビルディングブロックの工業的需要は大きい。不斉合成の研究は盛んであるが，低分子医薬品のプロセス化学では，例えば塩基性のラセミ体を酸性の光学分割剤と塩形成させるジアステレオマー塩法が一般的な光学分割法である。しかしながら，塩形成しない中性のラセミ体には適用できない。ホストとゲストが共結晶化する包接現象は中性分子でも一方の光学活性体ゲストを取り込んだ包接結晶の優先的晶出が可能である。さらにジアステレオマー包接結晶化をラセミ化条件下で行う結晶化誘起動的光学分割は，ラセミ体を光学活性体に変換できるキラルテクノロジーとしてその研究成果の意義は大きい。
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