合成含有1,2-氨基醇的基拉尔化合物,利用催化非对称转移化未受保护的α-基托胺
Hari P R Mangunuru1, Leila Terrab1, Venumadhav Janganati1
1TCG GreenChem, Inc., 701 Charles Ewing Blvd, Ewing, New Jersey 08628, United States.
The Journal of organic chemistry
|April 22, 2024
概括
一种新的催化方法简化了合成的1,2-氨基醇,这对于像上腺素这样的药物至关重要. 这种高效的过程克服了现有协议的局限性,有效地解决了药物短缺问题.
科学领域:
- 有机化学 有机化学
- 药用化学 医学化学
- 催化剂是一种催化剂.
背景情况:
- 随着COVID-19大流行,药物短缺问题显而易见,特别是对于诸如上腺素和上腺素之类的关键药物.
- 对于性1,2-氨基醇的现有合成途径通常是漫长的,需要保护/解除保护的步骤,阻碍了有效的药物生产.
- 需要精简,反选择性合成策略来满足全球制药需求.
研究的目的:
- 开发一种简单且高度抗选择性的合成策略,用于奇拉性1,2-氨基醇.
- 建立一种高效的合成上腺素和上腺素的方法,解决与流行病相关的药物短缺问题.
- 为了证明开发方法对各种含有1,2-氨基醇的药物分子的广泛适用性.
主要方法:
- 使用催化不对称转移化未受保护的α-基托胺.
- 开发了一步骤的上腺素合成过程和两步骤的上腺素合成过程.
- 应用合成烯,代诺巴胺,诺布丁林和莱维索普雷纳林的方法.
主要成果:
- 通过使用未受保护的α-基托氨基胺,实现了用于性1,2-氨基醇的简单合成策略.
- 开发了一种高度分离的 (>99% ee) 一步合成上腺素和两步合成上腺素.
- 成功合成了其他各种1,2-氨基醇药物分子,具有高的分离产量和出色的酶选择性.
结论:
- 研发的以为催化剂的不对称转移化提供了一种高效的,对有价值的性1,2-氨基醇进行酶选择的途径.
- 该方法为克服当前药物合成的局限性提供了切实可行的解决方案,有助于解决基本药物的短缺问题.
- 该策略具有多功能性,适用于一系列重要的药物化合物,证明了其在药物制造中的巨大潜力.
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