| 研究課題/領域番号 |
20K15269
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| 研究機関 | 北海道大学 |
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研究代表者 |
REYES RONALD・LAZO 北海道大学, 化学反応創成研究拠点, 特任助教 (30845475)
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| 研究期間 (年度) |
2020-04-01 – 2024-03-31
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| キーワード | asymmetric synthesis / borylation / organometallic catalysis / organic synthesis / C-H activation / C-H functionalization / remote C-H bonds / noncovalent interactions |
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| 研究実績の概要 |
I have developed a methodology for the activation and subsequent borylation of N-adjacent C(sp3)-H bonds under rhodium catalysis (J. Am. Chem. Soc. 2020, 142, 589-597). This provided access to a variety of isostructural boron analogues of amino acids including bioactive compounds like the anticancer drug, bortezomib. Collaborations with ICReDD scientists also opened new opportunities for the development of novel reactivities guided by calculated transition states that leads to the competent activation of remote C-H bonds. Through collaborative research work, the asymmetric borylation of remote gamma-C-H bonds in aliphatic carboxylic acid derivatives such as amides and esters were achieved (Science 2020, 369, 970-974). Tolerating a wide range of substrates, aliphatic secondary and tertiary carboxamides, as well as ester derivatives were amenable for the asymmetric borylation. An impressive tolerance towards unsaturation on the chain makes fatty acid-derived substrates including the amide derivative of linoleic acid, the doubly unsaturated essential omega-6 fatty acid, amenable to the asymmetric borylation. Linoleic acid was recently implicated in studies involving binding pockets in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike proteins, thus the developed protocol will find excellent applications in creating methodologies for introducing molecular complexity and chemical modification in fatty acids.
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| 現在までの達成度 (区分) |
現在までの達成度 (区分)
2: おおむね順調に進展している
理由
As described in the research achievement section, fruitful exchanges and collaborations with ICReDD scientists result to the publication of important papers in very prominent chemistry journal, JACS, and well acclaimed authoritative journal Science. Presently, we rely on the knowledge that we gained from these works. The project is running smoothly as planned. With the advent of the pandemic that is upon all of us, minor changes in the implementation was affected. This include the scheduling of experiments. Nonetheless, the project is continuing and operational.
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| 今後の研究の推進方策 |
In the onset of 2021, on the basis of our previous knowledge from collaborative work in ICReDD, I am working on the development of a catalytic system consists of a metal catalyst (Ir, Rh, etc.) and chiral ligand platform in generating an asymmetric field or a substrate binding cavity that will enable the activation and functionalization of remote C-H bonds. Our team plans to establish a new design concept leading to the discovery of the highly enantioselective remote C(sp3)-H borylation of aliphatic carboxylic amides and esters that occurs specifically at the position beyond the gamma-methylene group. We have made some progress in this aspect. Our preliminary results suggest that we can target more remote C-H bonds (i.e., epsilon-C-H in the aliphatic hydrocarbon) by modifying the receptor urea ligand while keeping the same catalytic system. We envisioned that computational information will help to expedite the development of effective catalyst to realize our goal in functionalizing remote C-H bonds in readily available starting materials such as hydrocarbon derivatives, fatty acids, and bioactive compounds. Through these collaborations, I am hoping that a modular approach for producing a chiral catalyst can lead to the discovery of novel reactivity guided by calculations and information science. This work, in particular, looks into the details and possibility of generating a catalytic pocket, a chemical space, or a cavity where chemical reactions can occur mimicking natural enzymes in their reactivities.
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| 次年度使用額が生じた理由 |
Unused funds are primarily due to the cancellation of various conferences and other avenues for research presentations and promotions. Business trips were cancelled due to the onset of the pandemic. The use of research facilities and the utilization of reagents and/or chemicals needed for the experimentation has also been reduced in some extent. The cost of research for the next fiscal year will encompass purchase of reagents and necessary equipment to make possible the implementation of the experimental design.
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