Xiao Xiao, Zhao Baoguo
The Education Ministry Key Lab of Resource Chemistry, Shanghai Key Laboratory of Rare Earth Functional Materials, and Shanghai Frontiers Science Center of Biomimetic Catalysis, Shanghai Normal University, Shanghai 200234, P. R. China.
Acc Chem Res. 2023 May 2;56(9):1097-1117. doi: 10.1021/acs.accounts.3c00053. Epub 2023 Apr 18.
One of the fundamental goals of chemists is to develop highly efficient methods for producing optically active compounds, given their wide range of applications in chemistry, pharmaceutical industry, chemical biology, and material science. Biomimetic asymmetric catalysis, which imitates the structures and functions of enzymes, has emerged as an extremely attractive strategy for producing chiral compounds. This field has drawn tremendous research interest and has led to various protocols for constructing complex molecular scaffolds. The Vitamin B family, including pyridoxal, pyridoxamine, pyridoxine, and the corresponding phosphorylated derivatives, serves as the cofactors to catalyze more than 200 enzymatic functions, accounting for ∼4% of all enzyme activities. Although significant progress has been made in simulating the biological roles of vitamin B during the past several decades, its extraordinary catalytic power has not yet been successfully applied into asymmetric synthesis. In recent years, our group has been devoted to developing vitamin B-based biomimetic asymmetric catalysis using chiral pyridoxals/pyridoxamines as catalysts. We are particularly interested in mimicking the processes of enzymatic transamination and biological aldol reaction of glycine, respectively, developing asymmetric biomimetic transamination and carbonyl catalysis enabled α-C-H transformation of primary amines. Using a chiral α,α-diarylprolinol-derived pyridoxal as the catalyst, we reported the first chiral pyridoxal catalyzed asymmetric transamination of α-keto acids in 2015. A significant breakthrough in biomimetic transamination was achieved by using an axially chiral biaryl pyridoxamine catalyst that bears a lateral amine side arm. The amine side arm acts as an intramolecular base, accelerating the transamination and proving highly effective for transamination of α-keto acids and α-keto amides. In addition, we discovered the catalytic power of chiral pyridoxals as carbonyl catalysts for asymmetric biomimetic Mannich/aldol reactions of glycinates. These chiral pyridoxals also enabled more α-C-H conversions of glycinates, such as asymmetric 1,4-addition toward α,β-unsaturated esters and asymmetric α-allylation with Morita-Baylis-Hillman acetates. Moreover, carbonyl catalysis can be further applied to highly challenging primary amines with inert α-C-H bonds, such as propargylamines and benzylamines, which represents a powerful strategy for direct asymmetric α-C-H functionalization of various primary amines without protection of the NH group. These biomimetic/bioinspired transformations provide efficient new protocols for the synthesis of chiral amines. Herein, we summarize our recent efforts on the development of the vitamin B-based biomimetic asymmetric catalysis.
鉴于光学活性化合物在化学、制药工业、化学生物学和材料科学等领域有着广泛的应用，化学家的一个基本目标是开发高效的方法来制备这些化合物。仿生不对称催化模仿酶的结构和功能，已成为一种极具吸引力的制备手性化合物的策略。该领域引起了巨大的研究兴趣，并产生了各种构建复杂分子骨架的方法。维生素B族，包括吡哆醛、吡哆胺、吡哆醇及其相应的磷酸化衍生物，作为辅因子催化200多种酶促功能，占所有酶活性的约4%。尽管在过去几十年中，在模拟维生素B的生物学作用方面取得了重大进展，但其非凡的催化能力尚未成功应用于不对称合成。近年来，我们小组致力于开发以手性吡哆醛/吡哆胺为催化剂的基于维生素B的仿生不对称催化。我们特别感兴趣的是分别模仿酶促转氨作用和甘氨酸的生物醛醇缩合反应过程，开发能实现伯胺α-C-H转化的不对称仿生转氨作用和羰基催化。2015年，我们以手性α,α-二芳基脯氨醇衍生的吡哆醛为催化剂，报道了首例手性吡哆醛催化的α-酮酸不对称转氨反应。使用带有侧胺侧链的轴向手性联芳基吡哆胺催化剂实现了仿生转氨作用的重大突破。胺侧链作为分子内碱，加速了转氨反应，并被证明对α-酮酸和α-酮酰胺的转氨反应非常有效。此外，我们发现手性吡哆醛作为羰基催化剂对甘氨酸酯的不对称仿生曼尼希/醛醇缩合反应具有催化能力。这些手性吡哆醛还能实现更多甘氨酸酯的α-C-H转化，如对α,β-不饱和酯的不对称1,4-加成以及与森田-贝利斯-希尔曼乙酸酯的不对称α-烯丙基化反应。此外，羰基催化还可进一步应用于具有惰性α-C-H键的极具挑战性的伯胺，如炔丙胺和苄胺，这代表了一种在不保护NH基团的情况下直接对各种伯胺进行不对称α-C-H官能化的有力策略。这些仿生/受生物启发的转化为手性胺的合成提供了高效的新方法。在此，我们总结了我们最近在开发基于维生素B的仿生不对称催化方面所做的努力。
