Atom-by-Atom Iterative Synthetic Logic: Laying the Foundation for Programmable Automated Construction of Small Organic Molecules.

IF 12.7 1区 化学 Q1 CHEMISTRY, MULTIDISCIPLINARY
ACS Central Science Pub Date : 2025-05-29 eCollection Date: 2025-06-25 DOI:10.1021/acscentsci.5c00526
Miao Chen, Guangbin Dong
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引用次数: 0

Abstract

Fully automated preparation of diverse small organic molecules remains a formidable challenge due to the inherent constraints of conventional synthetic philosophies. The existing automation approaches require access to either almost unlimited kinds of chemical reagents or custom-made building blocks (BBs). Herein we propose atom-by-atom iterative synthesis (AIS) as a new synthetic logic to tackle this challenge. By viewing complex organic molecules as assemblies of single-carbon- or heteroatom-based units, AIS aims to construct molecular skeletons through iterative coupling of simple atomic-scale BBs by a unified type of reactionboron homologations. Compared with conventional approaches, the AIS strategy uses only a few types of chemical reactions and a small set of BBs, making it more suitable for automation and artificial intelligence-assisted synthetic route design. To date, enormous progresses have been made on the synthetic chemistry that serves for the purpose of AIS, such as introducing heteroatoms and sp2-carbons, forming ring structures, developing thermostable carbenoid reagents, and achieving stereochemical controls. On the other hand, substantial challenges and limitations remain to be overcome for realizing fully automated construction of diverse molecules. This Outlook article describes the AIS concept, recent progress, current limitations, and future opportunities in this field.

原子-原子迭代合成逻辑:为有机小分子的可编程自动化构建奠定基础。
由于传统合成原理的固有限制,全自动制备各种小有机分子仍然是一个艰巨的挑战。现有的自动化方法需要使用几乎无限种类的化学试剂或定制的构建模块(BBs)。在此,我们提出原子迭代合成(AIS)作为一种新的合成逻辑来解决这一挑战。通过将复杂的有机分子视为单碳或杂原子基单元的组装,AIS旨在通过统一类型的反应硼同源化,通过简单原子尺度的BBs的迭代耦合构建分子骨架。与传统方法相比,AIS策略只使用几种化学反应类型和一小组BBs,使其更适合自动化和人工智能辅助合成路线设计。迄今为止,为AIS服务的合成化学已经取得了巨大的进展,例如引入杂原子和sp2碳,形成环结构,开发耐热类碳试剂以及实现立体化学控制。另一方面,要实现多样化分子的完全自动化构建,还需要克服大量的挑战和限制。这篇展望文章描述了AIS的概念、最近的进展、当前的限制以及该领域未来的机会。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
ACS Central Science
ACS Central Science Chemical Engineering-General Chemical Engineering
CiteScore
25.50
自引率
0.50%
发文量
194
审稿时长
10 weeks
期刊介绍: ACS Central Science publishes significant primary reports on research in chemistry and allied fields where chemical approaches are pivotal. As the first fully open-access journal by the American Chemical Society, it covers compelling and important contributions to the broad chemistry and scientific community. "Central science," a term popularized nearly 40 years ago, emphasizes chemistry's central role in connecting physical and life sciences, and fundamental sciences with applied disciplines like medicine and engineering. The journal focuses on exceptional quality articles, addressing advances in fundamental chemistry and interdisciplinary research.
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