多图合成二甲基斯泰兰-1,5-二碳酸盐作为基因前体的多甲基-基模拟器
Oleh K Smyrnov1,2, Kostiantyn P Melnykov1,2, Eduard B Rusanov3
1Enamine Ltd, 78 Winston Churchill Street, Kyiv, Ukraine.
Chemistry (Weinheim an der Bergstrasse, Germany)
|September 21, 2023
概括
研究人员开发了一种可扩展的合成新C(sp3) 丰富的多环碳化合物支架,为药物化学和作物科学应用提供和的生物异构体. 这些斯泰兰衍生物是传统二的有价值替代品.
科学领域:
- 有机化学 有机化学
- 药用化学 医学化学
- 材料科学 材料科学 材料科学
背景情况:
- 开发新的C(sp3) 丰富的多环碳化合物支架对于推进药物化学和作物科学至关重要.
- 二的和生物异构体具有独特的结构和电子特性.
- 现有的合成方法缺乏可扩展性和生产这些复杂支架的效率.
研究的目的:
- 开发一个可扩展和高效的三环[3.3.0.037]octane (stellane) 1,5-dicarboxylic 酸衍生物的合成协议.
- 为了在药物发现和农作物保护中为二类物质建立可贵的和生物异构体,使用斯泰伦支架.
- 阐明反应机制和立体化学控制在合成斯泰兰衍生物.
主要方法:
- 通过二甲基八氧化二甲基二二氧化酸 (DMOD) 的氧化循环制造,可扩展的合成斯泰兰1,5-二碳酸衍生物.
- DMOD立体异构体的化,其后是 (I2) 氧化.
- 进行X射线晶体分析以确定脚手架结构和拓.
- 密度函数理论 (DFT) 计算用于研究反应机制.
主要成果:
- 建立了一个可扩展的协议 (高达50克) 用于斯特兰1,5-二碳酸二甲基乙醇合成.
- X射线晶体学证实了斯泰兰基架作为一个最优的和异为正位异位.
- DMOD基质的立体化学决定了反应结果:exo,endo cis- 和 exo,exo cis- 异构体在定量上产生了所需的产物.
- DFT揭示了一种涉及二离子形成,单电子转移 (SET) 氧化和随后循环化的机制.
结论:
- 开发的合成路径提供了以前无法获得的C ((sp3) 丰富的多环碳化合物支架.
- 斯泰兰衍生物作为色胺的有效和生物异构体,在药物化学和作物科学中具有潜在的应用.
- 立体化学控制对于实现所需的恒产品的高产量至关重要,提供精确的分子设计.
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