On-DNA Transfer Hydrogenolysis and Hydrogenation for the Synthesis of DNA-Encoded Chemical Libraries
On-DNA Transfer Hydrogenolysis and Hydrogenation for the Synthesis of DNA-Encoded Chemical Libraries
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DNA 转移氢解和氢化用于合成 DNA 编码的化学文库
DOI：
10.1002/ange.202111927
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发表时间：
2021
影响因子：
--
通讯作者：
Stanway-Gordon H
中科院分区：
文献类型：
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作者：
Stanway-Gordon H
DNA编码库是寻找蛋白质小分子配体的一种日益流行的方法。许多DEL合成协议依赖于使用裂解池组合方法的单体的顺序加成。因此，相容的保护基团策略是非常可取的，该策略允许在单体偶联之前揭开反应性官能团(例如 G.胺和醇)的掩蔽，或者去除较不理想的官能团(例如 例如烯烃和炔烃)。氢化/氢解程序可以达到这些目的，但不适用于Del化学。本文报道了Pd/C、HCONH4和胶束形成表面活性剂TPGS-750-M的催化氢转移反应，该反应对CBZ保护的胺和苄基保护的醇的氢解以及硝基、卤化物、腈、醛、烯烃和炔烃的加氢都有很高的转化率。在编码化合物的多环合成中的应用与DNA扩增和测序完全兼容，证明了其在DEL合成中的适用性。该方法将使用正交保护基团来实现合成DEL序列。
DNA‐encoded libraries (DELs) are an increasingly popular approach to finding small molecule ligands for proteins. Many DEL synthesis protocols hinge on sequential additions of monomers using split‐pool combinatorial methods. Therefore, compatible protecting group strategies that allow the unmasking of reactive functionality (e. g. amines and alcohols) prior to monomer coupling, or the removal of less desirable functionality (e. g., alkenes and alkynes) are highly desirable. Hydrogenation/hydrogenolysis procedures would achieve these ends but have not been amenable to DEL chemistry. We report a catalytic hydrogen transfer reaction using Pd/C, HCONH4and the micelle‐forming surfactant, TPGS‐750‐M, which gives highly efficient conversions for hydrogenolysis of Cbz‐protected amines and benzyl protected alcohols and hydrogenation of nitros, halides, nitriles, aldehydes, alkenes and alkynes. Application to multicycle synthesis of an encoded compound was fully compatible with DNA‐amplification and sequencing, demonstrating its applicability to DEL synthesis. This method will enable synthetic DEL sequences using orthogonal protecting groups.