Graduate School of Biomedical Sciences, Tokushima University.
Chem Pharm Bull (Tokyo). 2021;69(4):303-313. doi: 10.1248/cpb.c21-00031.
Non-canonical amino acid derivatives are an attractive scaffold for novel drug candidates. Among the methods used to prepare this motif, the asymmetric Mannich-type reaction of α-imino carboxylic acid derivatives is a preeminent strategy because a wide variety of non-canonical amino acids can be accessed by changing only the nucleophile. Preparing the common substrate is difficult, however, which makes this method problematic. We developed a convenient method for synthesizing common substrates using MnO-mediated oxidation of stable precursors. Peptides bearing non-canonical amino acids are another attractive synthetic target. We propose a new approach for synthesizing non-canonical amino acid-containing peptides by directly applying various organic reactions to peptidic substrates. Using hydrophobic anchor-supported peptides, we directly applied ring-closing metathesis and asymmetric Friedel-Crafts reactions to peptidic substrates. We also developed a novel recyclable organocatalyst according to the nature of the hydrophobic anchor tagged compound.
非天然氨基酸衍生物是新型药物候选物的一种有吸引力的结构。在用于制备这种结构的方法中，α-亚氨基羧酸衍生物的不对称 Mannich 型反应是一种卓越的策略，因为通过仅改变亲核试剂就可以获得各种非天然氨基酸。然而，常见底物的制备很困难，这使得该方法存在问题。我们开发了一种使用 MnO 介导的稳定前体氧化来合成常见底物的简便方法。含有非天然氨基酸的肽是另一个有吸引力的合成目标。我们提出了一种通过直接将各种有机反应应用于肽底物来合成含非天然氨基酸的肽的新方法。使用疏水性锚定支持的肽，我们直接将闭环复分解反应和不对称 Friedel-Crafts 反应应用于肽底物。我们还根据疏水性锚定标记化合物的性质开发了一种新型可回收有机催化剂。
