Covering: January 2014-June 2025. Previous review: Natural Product Reports, 2014, 31, 1612Natural products (NPs) have long been foundational in medicine, from ancient herbal remedies to the discovery of transformative drugs like morphine and quinine. The mid-20th century marked a 'golden age' for antibiotic discovery from natural sources, which then expanded into other therapeutic areas. However, by the late 20th century, other technological advances had shifted NPs from being a central component of the discovery process to one of several options. This review explores the current role of NPs in pharmaceuticals by analysing NP-derived (NP-D) drugs approved since 2014 and clinical candidates in development as of the end of 2024. 58 NP-related drugs launched between January 2014 and June 2025 were identified, which included 45 NP and NP-D new chemical entities (NCEs) and 13 NP-antibody drug conjugates (NP-ADCs). Next, all 579 drugs-388 (67%) of which were NCEs and 191 (33%) were new biological entities (NBEs)-approved globally from 2014 to 2024 were analysed. In total, 56 (9.7%) of these 579 drugs were classified as NPs or NP-Ds using this review's NP definition: 44 NCEs (7.6% overall; 11.3% of NCEs) and 12 NP-ADCs (2.1% overall; 6.3% of NBEs). The number of new NP-D NCEs and NP-ADCs has fluctuated between 0 and 8 annually since 2014, with an average of five approvals per year. Next, 125 NP and NP-D compounds were identified that were undergoing clinical trials or in the registration phase at the end of December 2024. Thirty-three new pharmacophores not previously found in approved drugs are now in development; however, only one has been discovered in the past 15 years. This review highlights the enduring promise of NPs, despite their diminished role in drug discovery, and advocates for renewed emphasis on bioassay-guided isolation and mode of action studies to identify new drug leads.

Covering up to 2025Natural products (NPs) from the terrestrial biodiversity play a key role in oncology drug discovery. While historically identified through bioactivity-guided fractionation, recent advances in high-content screening (HCS) assays, metabolomics, and in silico modeling have significantly enhanced the potential and attractiveness of flora-derived NPs for the development of anticancer therapeutics. This includes immunomodulatory molecules that are able to target the tumor microenvironment to promote immune-mediated clearance of the tumor, thereby improving patient response. This review highlights the untapped potential of molecules extracted from the South Pacific's terrestrial flora in the search for novel antitumor and immunomodulatory compounds. The unique biodiversity of Oceania, including Australia, New Zealand, and Pacific Island Countries and Territories (PICTs) across Micronesia, Melanesia and Polynesia, offers a promising yet largely unexplored reservoir for discovering plant-derived molecules with antitumor and immunomodulatory activities. Herein, we examine the recent pharmacological advances in this field and highlight the need for sustainable and collaborative research. Leveraging cutting-edge technologies could help overcome the challenge of NP-based drug discovery on these geographically isolated islands, unlocking the region's vast potential for plant-derived cancer therapeutics.

Covering literature to September 2025This review provides a comprehensive account of the 217 natural product inspired antibiotics that have been approved for human use from 1943 through to September 2025, inclusive of 52 (24%) that are natural products (NPs) and 165 (76%) that are semi-synthetic or synthetic derivatives of natural products (NP-Ds). These are organized into sixteen categories defined by shared structural motifs and, in many cases, common mechanisms of action. Each antibiotic is classified as either a NP or NP-D, annotated by a molecular structure that, where relevant, highlights the relationships between NPs and NP-Ds. Market details are also provided, including the company that brought each antibiotic to market, the year and country of first approval, the spectrum of usage across pathogen classes, routes of administration, current status, and selected commentary on mechanisms of action. The assembled dataset is further analysed through a series of charts that illustrate insightful trends that document the remarkable history and lasting impact of NP inspired antibiotics. The review concludes with observations on the historic impact and future prospects of natural products as a source of inspiration for the development of new generations of antibiotics.

Covering 2015 to 2024Cycloaddition of nitrones with alkenes forms isoxazolidines, which are five-membered heterocycles containing nitrogen and oxygen atoms. This transformation functionalizes alkenes by forming C-C and C-O bonds. The N-O bond in the resultant isoxazolidines is easily cleaved. Additionally, when the cycloaddition is carried out intramolecularly, the regioselectivity of the reaction is influenced by the tether connecting the nitrone and alkene and can differ from the selectivity governed by frontier molecular orbital interaction. These features make the intramolecular cycloaddition of nitrones attractive in the synthesis of complex molecules. In this review, we discuss the intramolecular cycloaddition of nitrones used in the total synthesis of natural products.

Covering: 1961 to 2024Discovering and identifying unique natural products/biosignatures (signatures that can be used as evidence for past or present life) that are abundant, and complex enough that they indicate robust evidence of life is a multifaceted process. One distinct category of biosignatures being explored is organic compounds. A subdivision of these compounds not yet readily investigated are volatile organic compound (VOCs). When assessing these VOCs as a group (volatilome) a fingerprint of all VOCs within an environment allows the complex patterns in metabolic data to be unravelled. As a technique already successfully applied to many biological and ecological fields, this paper explores how analysis of volatilomes in terrestrial extreme environments could be used to enhance processes (such as metabolomics and metagenomics) already utilised in life detection beyond Earth. By overcoming some of the complexities of collecting VOCs in remote field sites, a variety of lab based analytical equipment and techniques can then be utilised. Researching volatilomics in astrobiology requires time to characterise the patterns of VOCs. They must then be differentiated from abiotic (non-living) signals within extreme environments similar to those found on other planetary bodies (analogue sites) or in lab-based simulated environments or microcosms. Such an effort is critical for understanding data returned from past or upcoming missions, but it requires a step change in approach which explores the volatilome as a vital additional tool to current 'Omics techniques.

Covering: up to 2025para-Quinone methides (p-QMs) are highly reactive Michael acceptors with broad applications in organic synthesis, drug development, and materials science. Nature ingeniously harnesses these intermediates for diverse biochemical processes, ranging from melanization to the biosynthesis of bioactive natural products. While some natural products incorporate stable p-QM moieties, most p-QMs are transient, serving as pivotal intermediates in various metabolic pathways. This highlight examines p-QM-mediated enzymatic transformations in natural product biosynthesis, emphasizing catalytic mechanisms, substrate flexibility, and engineering potential. Understanding these biosynthetic strategies would advance enzyme discovery, inspire biomimetic synthesis, and guide rational enzyme design efforts.

Covering: 2010 up to 2025 (May)Mycotoxins, secondary metabolites produced by filamentous fungi, are highly toxic contaminants of food crops. These contaminated plants pose a significant health risk to livestock and humans. Cereals are the main source of dietary mycotoxin intake in the EU and are often contaminated with Fusarium mycotoxins. After fungal infection, mycotoxins are produced and further modified by plant enzymes. The most common mechanism of modification of Fusarium mycotoxins and other mycotoxins is conjugation with glucose, but also with oligosaccharides and polysaccharides. Although this reduces their toxicity to the plant, enzymes in the gastrointestinal tract of animals or enzymes used in the food processing can hydrolyze the glycosidic bond, releasing the mycotoxin. While the analysis of free mycotoxins is routine, the quantification of mono-, oligo-, and polyglycosides is difficult or impossible, leading to an underestimation of the actual risk. Most conjugated mycotoxins cannot be routinely quantified as analytical standards are commercially unavailable. This review focuses in particular on the formation and occurrence of glycosylated mycotoxins and their effects on health and their transformations in the food chain. It summarizes and critically compares chemical, enzymatic, plant, and microbial glycosylation. Specific deglycosylation methods (both enzymatic and chemical) required for the evaluation of the content of respective mycotoxins are covered. Indirect quantification of modified mycotoxins using enzymatic hydrolysis methods and subsequent analysis of the free forms, typically performed by HPLC-MS, is discussed. The whole spectrum of mycotoxins, including those that are sometimes neglected in modern literature (typically ergot mycotoxins), is covered in a rather complex way.