Scale-Up Synthesis of 1-Methyladamantane and Its Functionalization as a Key Point for Promising Antiviral Agents,Organic Process Research & Development

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Scale-Up Synthesis of 1-Methyladamantane and Its Functionalization as a Key Point for Promising Antiviral Agents
Organic Process Research & Development ( IF 3.1 ) Pub Date : 2023-02-24 , DOI: 10.1021/acs.oprd.2c00305
Alexander E. Pashenko _{1,

2,

3} , Alexandr Gaidai _{1,

3,

4} , Nazar Hryhoriev _{1,

4} , Olesia Volovenko ₁ , Igor Levandovskiy ₄ , Olga Maksymenko ₁ , Dmitriy M. Volochnyuk _{1,

2,

3} , Sergey V. Ryabukhin _{1,

2,

3}

Affiliation

Methyladamantane and its derivatives are rare chemotypes for industrial and even wide research use. The proposed scalable and inexpensive approach to such compounds opens the door to further extensive study of biologically active derivatives based on this uncommon core. Optimized synthesis of the key precursor, the chiral (1S,3R,5R,7S)-3-methyl-5-phenyladamantane-1-carboxylic acid, showcases some significant innovations. The main one is very effective and cost-efficient stacked injections in preparative chiral chromatography and showed potential for enantioresolution of chiral cage compounds. Scaling the preparation of (1S,3R,5R,7S)-trans-N-(4-aminocyclohexyl)-3-methyl-5-phenyladamantane-1-carboxamide, which was recently shown to have notable activity against the Ebola virus, to multigram levels is an excellent example of our elaboration significance. It may push forward further biological investigation of this promising antiviral agent.

中文翻译：

1-甲基金刚烷的放大合成及其功能化作为有前途的抗病毒药物的关键点

甲基金刚烷及其衍生物是用于工业甚至广泛研究用途的罕见化学类型。拟议的此类化合物的可扩展且廉价的方法为进一步广泛研究基于这种不常见核心的生物活性衍生物打开了大门。关键前体手性 (1 S ,3 R ,5 R ,7 S )-3-methyl-5-phenyladamantane-1-carboxylic acid 的优化合成展示了一些重大创新。主要的一种是在制备型手性色谱中非常有效且具有成本效益的堆叠进样，并显示出手性笼化合物对映体拆分的潜力。缩放制备 (1 S ,3 R ,5 R ,7 S)- trans - N -(4-aminocyclohexyl)-3-methyl-5-phenyladamantane-1-carboxamide，最近被证明对埃博拉病毒具有显着的活性，达到多克水平，是我们阐述意义的一个很好的例子。它可能会推动对这种有前途的抗病毒药物进行进一步的生物学研究。

更新日期：2023-02-24

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