A Yb(OTf)3 and visible light relay catalyzed [3 + 2] cycloaddition/[3,3]-rearrangement/[4 + 2] cycloaddition in one pot was developed to prepare oxazonine-fused endoperoxides in good yields from N-vinyl nitrones and methylenecyclopropanes.

We report a Yb(OTf) 3 -catalyzed formal [7 + 2] cycloaddition for the preparation of ninemembered N-heterocycles bearing three stereocenters in good yields with high diastereoselectivity through a [3 + 2] cycloaddition/[3,3]-rearrangement cascade strategy from N-vinyl-α,β-unsaturated nitrones and methylenecyclopropanes. Preliminary studies show that the Yb(OTf) 3 catalyst accelerates the reaction affording kinetically controlled cis-diastereomers as the major products. The obtained ninemembered N-heterocycles are easily converted to useful derivatives for late-stage modification.

Ferroptosis, an iron-dependent form of selective cell death, is involved in the development of many cancers. However, the role of ferroptosis-related genes (FRGs) in kidney renal papillary cell carcinoma (KIRP) is unclear. In this study, we examined the mRNA expression profiles and clinical data of patients with KIRP from the TCGA cohort. Consequently, 41 differentially-expressed FRGs were screened using the limma package, and 17 prognostic-related FRGs were identified by survival analysis and univariate Cox regression analyses. Thereafter, a ferroptosis-related gene prognostic index (FRGPI) was constructed based on five FRGs (AKR1C3, SAT1, FANCD2, HSBP1 and SQLE), using lasso Cox and multivariate Cox regression analyses. KIRP patients with high FRGPI scores displayed worse outcomes. Furthermore, the FRGPI was shown to be a reliable independent prognostic factor in both the training and testing cohorts. Comprehensive analysis also showed that the FRGPI can distinguish gene mutation, functional enrichment of immune cells and molecular function-related pathways. Interestingly, low FRGPI score could be more benefit from immune checkpoint inhibitors (ICIs) therapy. Then, the two hub prognostic genes (AKR1C3 and FANCD2) as a risk gene for KIRP were identified based on the FRGPI module, and the expression profiles of these two genes were validated using human KIRP cells, besides, we furthermore discovered that Fancd2 is significantly up-regulated in most cancers and is associated with prognosis. In conclusion, these findings showed that FRGPI can accurately predict the prognosis of patients with KIRP, suggesting that this risk model is a promising prognostic biomarker for these patients. Moreover, targeting ferroptosis (FANCD2) could be a potential therapeutic alternative for various cancers.

Nine-membered N-heterocycle scaffolds are widely found in natural products and biologically active molecules. The rigid structure of the medium-sized ring plays important roles in the regulation of their biological and pharmacological activities. Therefore, nine-membered N-heterocycle is one of the most attractive medium-sized ring compounds. Because of the increasing entropy and ring extension of nine-membered ring skeleton, the synthesis of nine-membered N-heterocycles is still difficult; especially the effective control of substituent stereoselectivity for the nine-membered ring is one of the greatest challenging topics This review summarizes the novel synthetic strategies of nine-membered N-heterocycles and their applications in the synthesis of natural products and pharmaceutically active molecules containing nine-membered ring scaffold in recent years. Keywords nine-membered N-heterocycles; medium-sized ring compounds; cyclization; cycloaddition; ring expansion 氮杂环结构广泛存在天然产物和药物分子中, 是新 药设计和分子药理活性研究中的优势骨架 [1] . 中环骨架 (8～12 元环)的氮杂环化合物在自然界中广泛存在, 由 于环张力和熵增不利的影响, 中环骨架化合物的构建一 直是有机合成中极富挑战的难点之一 [2] . 其中, 九元氮 杂环化合物是最被关注的中环化合物之一 [3] . 如生物碱 antaroide [4] , (±)-cleavamine [5] , melohenine B [6] , (＋)-lycoposerramine B [7] , (-)-rhazinilam [8] , palhinine A [9] 等(图 1).