Biogen, Durham, North Carolina 27709, United States.
Department of Chemistry, University of Nebraska-Lincoln, Lincoln, Nebraska 68588, United States.
Chem Rev. 2022 Aug 24;122(16):13800-13880. doi: 10.1021/acs.chemrev.2c00213. Epub 2022 Jul 29.
Reaction discovery and catalyst screening lie at the heart of synthetic organic chemistry. While there are efforts at catalyst design using computation/artificial intelligence, at its core, synthetic chemistry is an experimental science. This review overviews biomacromolecule-assisted screening methods and the follow-on elaboration of chemistry so discovered. All three types of biomacromolecules discussed─enzymes, antibodies, and nucleic acids─have been used as "sensors" to provide a readout on product chirality exploiting their native chirality. Enzymatic sensing methods yield both UV-spectrophotometric and visible, colorimetric readouts. Antibody sensors provide direct fluorescent readout upon analyte binding in some cases or provide for cat-ELISA (Enzyme-Linked ImmunoSorbent Assay)-type readouts. DNA biomacromolecule-assisted screening allows for templation to facilitate reaction discovery, bimolecular reactions into a pseudo-unimolecular format. In addition, the ability to use DNA-encoded libraries permits the barcoding of reactants. All three types of biomacromolecule-based screens afford high sensitivity and selectivity. Among the chemical transformations discovered by enzymatic screening methods are the first Ni(0)-mediated asymmetric allylic amination and a new thiocyanopalladation/carbocyclization transformation in which both C-SCN and C-C bonds are fashioned sequentially. Cat-ELISA screening has identified new classes of sydnone-alkyne cycloadditions, and DNA-encoded screening has been exploited to uncover interesting oxidative Pd-mediated amido-alkyne/alkene coupling reactions.
反应发现和催化剂筛选是合成有机化学的核心。虽然有使用计算/人工智能进行催化剂设计的努力，但合成化学本质上是一门实验科学。本篇综述概述了生物大分子辅助筛选方法以及后续对所发现化学物质的阐述。所讨论的三种生物大分子——酶、抗体和核酸——都被用作“传感器”，利用其固有手性，提供产物手性的读出。酶感应方法可提供紫外分光光度法和可见、比色法读数。在某些情况下，抗体传感器在分析物结合时提供直接荧光读数，或者提供 cat-ELISA（酶联免疫吸附测定）类型的读数。DNA 生物大分子辅助筛选允许模板化以促进反应发现，将双分子反应转化为拟单相格式。此外，使用 DNA 编码文库的能力允许反应物的条形码化。所有三种基于生物大分子的筛选方法都具有高灵敏度和选择性。通过酶筛选方法发现的化学转化包括首次 Ni(0)介导的不对称烯丙基胺化反应和新的硫氰酸钯化/碳环化反应，其中 C-SCN 和 C-C 键顺序形成。cat-ELISA 筛选已鉴定出新型 sydnone-alkyne 环加成反应，而 DNA 编码筛选则被用于发现有趣的氧化 Pd 介导的酰胺-炔烃/烯烃偶联反应。
