Department of Chemical Sciences, Indian Institute of Science Education and Research (IISER) Mohali, Knowledge City, Sector 81, SAS Nagar, Mohali, Manauli P.O., Punjab, 140306, India.
Org Biomol Chem. 2022 Jun 1;20(21):4391-4414. doi: 10.1039/d2ob00658h.
We report the synthesis of carbazole-based unnatural α-amino acid and non-α-amino acid derivatives a Pd(II)-catalyzed bidentate directing group 8-aminoquinoline-aided β-C(sp)-H activation/functionalization method. Various -phthaloyl, DL-, L- and D-carboxamides derived from their corresponding α-amino acids, non-α-amino acids and aliphatic carboxamides were subjected to the β-C(sp)-H functionalization with 3-iodocarbazoles in the presence of a Pd(II) catalyst to afford the corresponding carbazole moiety installed unnatural amino acid derivatives and aliphatic carboxamides. Carbazole motif-containing racemic (DL) and enantiopure (L and D) amino acid derivatives including phenylalanine, norvaline, leucine, norleucine and 2-aminooctanoic acid with -stereochemistry and various non-α-amino acid derivatives including GABA have been synthesized. Removal of the 8-aminoquinoline directing group, deprotection of the phthalimide moiety and the preparation of carbazole amino acid derivatives containing free amino- and carboxylate groups are shown. The carbazole motif is prevalent in alkaloids and biologically active molecules and functional materials. Thus, this work on the synthesis of carbazole-based unnatural amino acid derivatives would enrich the libraries of unnatural amino acid derivatives and carbazoles.
我们报告了咔唑基非天然α-氨基酸和非α-氨基酸衍生物的合成，这是一种 Pd(II) 催化的双齿导向基团 8-氨基喹啉辅助的β-C(sp)-H 活化/官能化方法。各种 -邻苯二甲酰基、DL-、L-和 D-羧酸酰胺，来源于它们相应的α-氨基酸、非α-氨基酸和脂肪族羧酸酰胺，在 Pd(II) 催化剂存在下，与 3-碘咔唑进行β-C(sp)-H 官能化，得到相应的咔唑部分安装的非天然氨基酸衍生物和脂肪族羧酸酰胺。含有咔唑结构的外消旋（DL）和对映纯（L 和 D）氨基酸衍生物，包括苯丙氨酸、正缬氨酸、亮氨酸、正亮氨酸和 2-氨基辛酸，具有β-立体化学，以及各种非α-氨基酸衍生物，包括 GABA，都已被合成。已经展示了去除 8-氨基喹啉导向基团、脱保护邻苯二甲酰亚胺部分以及制备含有游离氨基和羧基的咔唑氨基酸衍生物。咔唑结构在生物碱和生物活性分子和功能材料中很常见。因此，这项关于咔唑基非天然氨基酸衍生物合成的工作将丰富非天然氨基酸衍生物和咔唑的文库。
