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Solid-phase Synthesis of [4.4] Spirocyclic Oximes
Published on: February 6, 2019
基于异酸盐的多组分反应与单过程相结合:以多样性为导向的结构型模拟物合成的高效工具
Bhavna Kaveti1, Manuel A Rentería-Gómez1, Alejandro Corona-Díaz1
1Departamento de Química, División de Ciencias Naturales y Exactas, Universidad de Guanajuato, Noria Alta S/N, Col. Noria Alta, Guanajuato, C.P., 36050, Gto., México.
以多样性为导向的合成 (DOS) 使用基于异酸盐的多元组分反应 (IMCR) 和循环添加,创建构造性定化. 这产生了具有异环生物异构体的复杂分子,如1,2,3-triazoles,有利于船形构造.
科学领域:
- 有机化学 有机化学
- 药用化学 医学化学
- 计算化学计算化学
背景情况:
- 类模拟剂模仿结构用于治疗应用.
- 2,5-Diketopiperazines (2,5-DKP) 是重要的结构支架.
- 胺基键生物异构体提供了增强的稳定性和多样化的特性.
研究的目的:
- 开发一种以多样性为导向的合成 (DOS) 策略,用于构造性定化学.
- 在2,5-DKP结构中将异环生物异构体,如1,2,3-三和1,5-异位四 (1,5-DS-T) 纳入.
- 探索合成分子的结构偏好和支架多样性.
主要方法:
- 使用基于异酸盐的多元组分反应 (IMCR),特别是Ugi-4CR和Ugi-Azide (UA).
- 采用单SN2/内分子酸循环添加 (IAAC) 反应.
- 进行DFT计算以确认分子构造.
主要成果:
- 基于2,5-DKP. 的结构性形模仿剂的成功合成.
- 证明了1,2,3-triazole环在诱导对船体构造的偏好方面的关键作用.
- 使用UA反应在N-1α-碳中产生了支架多样性,从而产生了新的三环皮多米特基与1,5-DS-T生物异构体.
结论:
- 联合的IMCR和IAAC战略有效地产生了复杂的,形状受约束的型模拟剂.
- 异环生物异构体显著影响合成分子的结构格局.
- 这种方法可以获得新型结构性型模拟剂,在药物发现中具有潜在的应用.
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