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Chronic obstructive pulmonary disease (COPD) is a highly prevalent disease that has become the third leading cause of death worldwide. Cycloastragenol (CAG), which is the genuine sapogenin of the main active triterpene saponins in Astragali radix , is a bioavailable pre-clinical candidate for chronic obstructive pulmonary disease (COPD), and it was investigated in our previous study. In order to progress medical research, it was first efficiently produced on a 2.5-kg scale via Smith degradation from astragaloside IV (AS-IV). Simultaneously, since the impurity profiling of a drug is critical for performing CMC documentation in pre-clinical development, a study on impurities was carried out. As these structures do not contain chromophores and possess weak UV absorption characteristics, HPLC-CAD and UPLC-LTQ-Orbitrap-MS were employed to carry out the quality control of the impurities. Then, column chromatography (CC), preparative thin-layer chromatography (PTLC), and crystallization led to the identification of 15 impurities from CAG API. Among these impurities, compounds 1, 4 , 9 , 10 , 14 , and 15 were elucidated via spectroscopic analysis, and 2 - 3, 5 - 8 , and 11 - 13 were putatively identified. Interestingly, the new compounds 9 and 14 were rare 10, 19-secocycloartane triterpenoids that displayed certain anti-inflammatory activities against LPS-induced lymphocyte cells and CSE-induced MLE-12 cells. Additionally, a plausible structural transformation pathway of the degradation compounds from CAG or AS IV was proposed. The information obtained will provide a material basis to carry out the quality control and clinical safety assurance of API and related prescriptions. Reasonable guidance will also be provided regarding the compounds with weak UV absorption characteristics.

Natural products (NPs) have historically played a primary role in the discovery of small-molecule drugs. However, due to the advent of other methodologies and the drawbacks of NPs, the pharmaceutical industry has largely declined in interest regarding the screening of new drugs from NPs since 2000. There are many technical bottlenecks to quickly obtaining new bioactive NPs on a large scale, which has made NP-based drug discovery very time-consuming, and the first thorny problem faced by researchers is how to dereplicate NPs from crude extracts. Remarkably, with the rapid development of omics, analytical instrumentation, and artificial intelligence technology, in 2012, an efficient approach, known as tandem mass spectrometry (MS/MS)-based molecular networking (MN) analysis, was developed to avoid the rediscovery of known compounds from the complex natural mixtures. Then, in the past decade, based on the classical MN (CLMN), feature-based MN (FBMN), ion identity MN (IIMN), building blocks-based molecular network (BBMN), substructure-based MN (MS2LDA), and bioactivity-based MN (BMN) methods have been presented. In this paper, we review the basic principles, general workflow, and application examples of the methods mentioned above, to further the research and applications of these methods.

Sesquiterpenoids constitute a marvelously varied group of natural products that feature a vast array of molecular architectures. Among them, the unusual bicyclo [6.3.0] undecane sesquiterpenoids are one of the most representative. To date, only approximately 42 naturally occurring compounds with this unique scaffold, which can be classified into seven different groups, have been reported. As the first-found member of each type, dactylol, asteriscanolide, dumortenol, toxicodenane C, and capillosanane S are characteristic of the four methyl groups on the five-eight-membered ring system. Only 11-hydroxyjasionone and sinuketal decorate the core with an isopropyl group. These natural products exhibit a wide range of bioactivities, including antifouling, anti-inflammatory, immune suppression, cytotoxic, antimutagenic, antiplasmodial, and antiviral activities. It was noted that some total syntheses of precapnellane-sesquiterpenoids (dactylol, poitediol, precapnelladiene), asteriscanolide, and 11-hydroxyjasionone have been achieved, because their cyclooctanoid core represents an important target for the development of synthetic strategies to prepare eight-membered ring-containing compounds. This review focuses on these natural sesquiterpenoids and their biological activities and synthesis, and aims to provide a foundation for further research of these interesting compounds.