In this study, two previously undescribed nitrogen-containing compounds, penisimplicins A (1) and B (2), were isolated from Penicillium simplicissimum JXCC5. The structures of 1 and 2 were elucidated on the basis of comprehensive spectroscopic data analysis, including 1D and 2D NMR and HRESIMS data. The absolute configuration of 2 was determined by Marfey’s method, ECD calculation, and DP4+ analysis. Both structures of 1 and 2 feature an unprecedented manner of amino acid-derivatives attaching to a polyketide moiety by C-C bond. The postulated biosynthetic pathways for 1 and 2 were discussed. Additionally, compound 1 exhibited significant acetylcholinesterase inhibitory activity, with IC₅₀ values of 6.35 μM.

Nitrogen-containing core structure pyrimidine has long been regarded as one of the privileged scaffolds for novel drug development. Natural products embedded with pyrimidine motifs are distinguished by their exceptional scaffold diversity and vast structural complexity, which endow them with versatile biological activities, including anticancer, antiviral, antifungal and anti-inflammatory activities. This review is dedicated to surveying a series of structurally distinctive naturally occurring compounds characterized by the presence of an aromatic heterocyclic pyrimidine moiety covering from 2004 to early 2025. Multiple key aspects of these 156 pyrimidine-containing compounds, including natural sources, features of chemical structure, biological activities, as well as biosynthetic studies are summarized. The review emphasizes the enduring potential of natural products, highlighting their inherent capacity for medication and optimization to fuel the pipeline of lead compound targeting major disease and providing new window for overview of these pyrimidine-containing natural products. Overall, this review aims to unlocking the potential of these isolates. It thus offers a fresh reference for the exploitation of pyrimidine-containing natural products, with the ultimate goal of realizing their therapeutic potential. Graphical Abstract

Ent-abietane diterpenoids constitute a class of terpenes with a C₂₀ carbon skeleton that underlie a wide range of biological activities. Ent-abietane diterpenoids, enantiomeric to the abietane counterparts, represent a family of diterpenoid natural products characterized by their distinct 6/6/6 tricyclic carbocyclic skeletons with exceptional structural complexity. An increasing number of these ent-abietane diterpenoids have recently been identified, constituting a well-defined group of naturally occurring compounds. This review provides a comprehensive summary of the natural sources, chemical structures, biological profiles and total synthesis of these ent-abietane diterpenoids from 2016 to early 2025.