Velezheva V S, Babii O L, Khodak A A, Alekseeva E A, Nelyubina Yu V, Godovikov I A, Peregudov A S, Majorov K B, Nikonenko B V
A. N. Nesmeyanov Institute of Organoelement Compounds of Russian Academy of Sciences Vavilova St. 28 119991 GSP-1, Moscow Russia
Laboratory for Immunogenetics, Central Institute for Tuberculosis Moscow Russia.
RSC Adv. 2019 Dec 13;9(71):41402-41408. doi: 10.1039/c9ra07807j.
Novel continuous-flow cascade reactions are developed for producing 1,4-diaryl-disubstituted dipolar γ-carbolines 2 that contain a carboxylate group and their two pentacyclic precursors 6, 7 from hemiindigos 1. The nucleophilic and pro-electrophilic chemistry described is new to the hemiindigos 1, and it led to the discovery of antimycobacterial scaffold characteristic of rimino-type pentacycles 6, 7 and potent drug clofazimine. The new scaffold like clofazimine appears to be useful in developing lead agents active against drug-resistant/dormant TB.
开发了新型连续流级联反应，用于从半靛蓝1制备含有羧酸盐基团的1,4 - 二芳基二取代偶极γ-咔啉2及其两种五环前体6、7。所描述的亲核和亲电化学对于半靛蓝1来说是全新的，并且导致发现了利米诺型五环6、7的抗分枝杆菌支架特征以及强效药物氯法齐明。像氯法齐明这样的新支架似乎有助于开发对抗耐药/潜伏性结核病有效的先导药物。
