Cho Soohyeon, Gu Lina, In Ik Joon, Wu Bo, Lee Taehoon, Kim Hakwon, Koo Sangho
Department of Energy Science and Technology, Department of Chemistry, Myongji University Myongji-Ro 116, Cheoin-Gu Yongin Gyeonggi-Do 17058 Korea
School of Pharmacy, East China University of Science and Technology Meilong Road 130 Shanghai 200237 China.
RSC Adv. 2021 Sep 23;11(50):31511-31525. doi: 10.1039/d1ra06110k. eCollection 2021 Sep 21.
One-pot conversion of sustainable d-ribose with l-amino acid, methyl esters produced pyrrole-2-carbaldehydes 5 in reasonable yields (32-63%) under pressurized conditions of 2.5 atm at 80 °C. The value-added pyrraline compounds 5 as platform chemicals were utilized for quick installation of poly-heterocyclic cores for the development of pyrrole-motif natural and artificial therapeutic agents. A pyrrole-fused piperazin-2-one scaffold 6 was prepared by reductive amination of pyrralines 5 with benzylamine. While further cyclization of pyrralines 5 with ethane-1,2-diamine produced pyrrolo-piperazin-2-ones 7 with an extra imidazolidine ring, the reaction with 2-amino alcohols derived from natural l-amino acids, alanine, valine, and phenylalanine, respectively provided pyrrolo-piperazin-2-ones 8, 9, and 10 with oxazolidine as the third structural core. Cell viability and an anti-inflammatory effect of the synthesized compounds were briefly tested by the MTT method and the Griess assay, among which 8h and 10g exhibited significant anti-inflammatory effects with negligible cell toxicity.
在80℃、2.5个大气压的加压条件下，可持续的d-核糖与l-氨基酸甲酯一锅法转化生成吡咯-2-甲醛5，产率合理（32-63%）。作为平台化学品的增值吡咯啉化合物5被用于快速构建多杂环核心，以开发吡咯基序的天然和人工治疗剂。通过吡咯啉5与苄胺的还原胺化反应制备了吡咯并哌嗪-2-酮支架6。虽然吡咯啉5与乙二胺进一步环化生成带有额外咪唑烷环的吡咯并哌嗪-2-酮7，但与分别衍生自天然l-氨基酸丙氨酸、缬氨酸和苯丙氨酸的2-氨基醇反应，分别得到了以恶唑烷为第三个结构核心的吡咯并哌嗪-2-酮8、9和10。通过MTT法和Griess试验对合成化合物的细胞活力和抗炎作用进行了简要测试，其中8h和10g表现出显著的抗炎作用，细胞毒性可忽略不计。
