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一种只用蓝光从六元环中除去硫、氮或氧原子的反应 精选

已有 2888 次阅读 2021-8-29 10:33 |个人分类:新观察|系统分类:博客资讯

一种只用蓝光从六元环中除去硫、氮或氧原子的反应

 诸平

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Approaches to piperidine diversification. (A) Peripheral functionalization and skeletal remodeling. (B) Selected examples of ring contractions on piperidine frameworks. (C) Seminal report of Seebach and co-workers’ unusual THIQ ring contraction (20). (D) Contraction of carbohydrates reported by Suárez and co-workers (21). (E) Norrish type II approach to piperidine skeletal framework modification (this work). Credit: Science(2021). DOI: 10.1126/science.abi7183

Bob Yirka 2021827日在物理学家组织网(Phys.org)发表的报道,美国加利福尼亚伯克利分校(University of California, Berkeley)的一个化学家小组与美国默克公司(Merck & Co., Inc.)的一个小组合作,开发了一种反应,可以只用蓝光从六元环中去除单个硫、氮或氧原子(A reaction that removes sulfur, nitrogen or oxygen atoms from six-membered rings using only blue light)。他们的研究结果于2021827日已经在《科学》(Science)杂志网站上发表——Justin Jurczyk, Michaelyn C. Lux, Donovon Adpressa, Sojung F. Kim, Yu-hong Lam, Charles S. Yeung, Richmond Sarpong. Photomediated ring contraction of saturated heterocycles. Science, 27 Aug 2021: Vol. 373, Issue 6558, pp. 1004-1012. DOI: 10.1126/science.abi7183. https://science.sciencemag.org/lookup/doi/10.1126/science.abi7183.

在此论文中,该小组描述了他们的反应以及它在各种应用中的可能用途。上述图示是哌啶(piperidine)多样化的途径。(A)表示外周功能化和骨架重塑。(B)表示哌啶框架上的环收缩举例。(C)表示塞巴赫(Seebach)以及合作者异常THIQ环收缩的开创性报告。(D) 表示苏亚雷斯(Suárez)以及合作者报告的碳水化合物收缩。(E)表示诺里什(NorrishII型方法对哌啶骨架结构的修饰(本项研究)

近年来,化学家们已经找到了控制碳环(carbon rings)的方法,这些碳环被用于制造大量的药品和农用化学品,但大多数方法都很复杂,很难操作。它们通常也需要消耗大量的能源。在这项新的努力中,研究人员发现了一种方法,可以打破饱和杂环环中的CSCOCN键,移除一个原子,之后只使用蓝光(blue light),环重新闭合,减少一个原子。 

为了进行反应,研究人员首先将一个芳香酮基团(附在杂环上)暴露在蓝色LED光(blue LED light)下。这引发了诺里什反应(Norrish reaction),其中一个碳杂原子键(carbon-heteroatom bond)被断裂,导致环的打开和一个原子的排出。这是可行的,因为它导致了一种核心激进分子(core radical)的产生。反应的第二部分涉及环的闭合,研究小组注意到,闭合过程与曼尼希反应(Mannich reaction)类似。他们指出,要使反应起作用,光的波长必须与起始物质中的羰基(carbonyl)完全匹配。他们还注意到,分子中没有原子被移除,也没有添加任何原子——结构只是简单地重新排列,留下了一个五元环。

研究人员注意到,尽管反应很简单,但它是操纵药物化学基石的游戏规则改变者。他们还注意到,该反应可能与其他反应结合使用,提供1-2冲孔式反应(1-2 punch sort of reaction),一次进行不止一种修饰。他们用它来编辑多种知名药物,如甲氟喹(mefloquine)和利米特罗(rimiterol),证明了这种反应的有效性。他们还指出,他们的新目标是找到一种方法,将芳香酮(aromatic ketone)添加到饱和杂环上。上述介绍,仅供参考。欲了解更多信息敬请注意浏览原文或者相关报道

Shuffling nitrogen with a light push

Manipulation of carbon–nitrogen rings is integral to the synthesis of numerous pharmaceutical and agrochemical compounds. Jurczyk et al. report that photoexcitation of carbonyl-substituted cyclic amines can shift the nitrogen from inside to outside the ring framework. The reaction appears to proceed through a 1,5-hydrogen shift to the electronically excited carbonyl, which sets in motion the subsequent carbon–nitrogen and carbon–carbon bonding rearrangements. Several oxygen and sulfur heterocycles were applicable as well. Addition of a chiral phosphoric acid catalyst rendered the reaction asymmetric.

Science, abi7183, this issue p. 1004

Abstract

Saturated heterocycles are found in numerous therapeutics and bioactive natural products and are abundant in many medicinal and agrochemical compound libraries. To access new chemical space and function, many methods for functionalization on the periphery of these structures have been developed. Comparatively fewer methods are known for restructuring their core framework. Herein, we describe a visible light–mediated ring contraction of α-acylated saturated heterocycles. This unconventional transformation is orthogonal to traditional ring contractions, challenging the paradigm for diversification of heterocycles including piperidine, morpholine, thiane, tetrahydropyran, and tetrahydroisoquinoline derivatives. The success of this Norrish type II variant rests on reactivity differences between photoreactive ketone groups in specific chemical environments. This strategy was applied to late-stage remodeling of pharmaceutical derivatives, peptides, and sugars.



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