利用含硼醛類合成胜肽異腈硼酯(I) 含硼胜肽四唑衍生物之合成(II) 依照Ugi-Passerini反應順序合成含硼衍生物(III)

Synthesis of Peptidyl Isocyano Boronate Ester using Boron-containing Aldehydes (I) Synthesis of Peptidyl Boron-containing Tetrazole Analogs (II) Synthesis of Boron-containing Analogs using Sequential Ugi 4CR/Passerini-3CR Reactions (III)

陳賢祺(Hsien-Chi Chen)

指導教授 ： 潘伯申

淡江大學/理學院/化學學系碩士班/碩士(2016年)

https://doi.org/10.6846/TKU.2016.00923

摘要

利用含硼醛類合成胜肽異腈硼酯(I)
根據文獻報導，近年來已知上百種含有異腈官能基 (Isocyanide) 之天然物。而這些特殊的天然物在抗菌或抗腫瘤上具有顯著的特效。所以，異腈化合物之合成實為一值得探討的研究主題。本研究成功藉由Ugi多組成反應合成出含硼之甲醯胺，接著成功地將之脫水轉換為含硼之異腈化合物。
含硼胜肽四唑衍生物之合成(II)
根據文獻指出，含四唑結構之化合物，具有相當顯著的生物活性。在藥物化學上，此結構可以取代羰基結構，在提供與羰基相同的化學鍵結作用力之外，此官能基之代謝穩定度亦遠優於羰基。因此，四唑化合物的合成值得深入探討。本研究成功藉由含硼異腈化合物進行合環，生成含硼之四唑化合物。
依照Ugi-Passerini反應順序合成含硼衍生物(III)
根據文獻記載，許多天然物皆含有depsipeptide結構。因此本研究將合成包含此官能基之含硼化合物作為目標。首先，我先利用Ugi-3CR合成出具有甲醯胺官能基之含硼雙胜肽化合物，接著進行脫水反應，轉化為相對應之含硼異腈化合物。最後在使用Passerini-3CR合成出具備含硼之depsipeptide化合物。

關鍵字

含硼異腈 ； 多組成反應 ； 含硼四唑雜環

並列摘要

1. Synthesis of Peptidyl Isocyano Boronate Ester using Boron-containing Aldehydes :
Isocyanide (or isonitrile) is a unique class of functional groups that appears in many biological active natural products. Many of these isocyanide-based natural products can be used as antitumor agents or antibiotics. Thus, incorporation of this functional group could potentially generate a biological interesting compound.
In the first part of my research, I have successfully synthesized 2 boron-containing formamides by microwave assisted Ugi-3CR in good yields (92%-97%). At the same time, I have successfully converted these 2 boron-containing formamides to the corresponding boron-containing isocyanides.
2. Synthesis of Peptidyl Boron-containing Tetrazole Analogs :
Tetrazole derivatives are often recognized for their impressive biological activities. The tetrazole ring is considered as a bioisostere of carboxylic acid, which possess a much-improved metabolic stability.
In the second part of my research, I have successfully synthesized 2 boron-containing tetrazoles by microwave.
3. Synthesis of Boron-containing Analogs using Sequential Ugi 4CR/Passerini-3CR Reactions :
Depsipeptide is a class of functional groups that frequently appears in variety of natural products. It composes of one ester group with at least one peptide bond(s). Therefore, inclusion of this functional group to the boron-containing compounds might generate interesting biologically active compounds.
In the third part of my research, I have utilized Ugi-3CR to synthesize boron-containing formamides via microwave irradiation. These formamides were subjected to dehydration process where the corresponding isocyanides were obtained. The desired boron-containing isocyanides were then utilized as one of the building blocks in the Passerini-3CR to generate boron-containing depsipeptide analogs.

並列關鍵字

Boron-containing isocyanide ； Multicomponent reaction ； Boron-containing tetrazole

參考文獻

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