This review systematically categorizes recent advances in the total synthesis of these alkaloids based on core-ring-closure strategies, highlighting innovations in reaction design and underscores the importance of modular, catalytic, and bio-inspired methods for future alkaloid synthesis.
Abstract
Covering: up to 2025Protoberberine alkaloids (PBs) and tetrahydroprotoberberine alkaloids (THPBs) exhibit diverse pharmacological activities, driving significant interest in their efficient synthesis. This review systematically categorizes recent advances in the total synthesis of these alkaloids based on core-ring-closure strategies. For protoberberines, key methodologies include transition-metal-catalyzed coupling, C-H activation, Mannich/Friedel-Crafts reactions, and tandem cyclizations, enabling the rapid construction of the tetracyclic skeleton. In chiral THPB synthesis, asymmetric strategies, such as chiral auxiliaries, organocatalysis, and transition-metal-catalyzed asymmetric reactions, address the stereochemical challenges at the C14 position. Enzymatic and chemoenzymatic approaches further complement chemical synthesis by enhancing stereocontrol and sustainability. By critically analyzing the efficiency, scope, and limitations of existing strategies, this review highlights innovations in reaction design and underscores the importance of modular, catalytic, and bio-inspired methods for future alkaloid synthesis.
Euphorbia diterpenoids are a structurally diverse class of natural products renowned for their potent biological activities. Inspired by biosynthetic 1,2-migrations, yet deliberately departing from these pathways, we developed a synthetic strategy that provides collective access to multiple distinct skeletal families through relay rearrangements. Central to this approach is the photochemical ring contraction of pyridinium salts, followed by aziridine-mediated diversification, to construct highly functionalized cyclopentane cores. These intermediates could be transformed into the euphorstranoid scaffold via a retro-aldol/transannular aldol sequence that enables stereocenter inversion, and into the pepluanol scaffold through a rare cationic [3,4]-rearrangement. This unified strategy not only enables the total syntheses of (+)-resiniferatoxin, (-)-euphorstranoid B, and (+)-pepluanol A, but also establishes a modular platform for complex carbocycle assembly in terpenoid synthesis.
Ling-Ran Kong, Jun-Long Qin, Hang Yu et al.· Journal of the American Chem...· 0 citations
This review compares the historical and methodological trajectories that have shaped IA and AA pathway elucidation, from compound isolation, radiotracer experiments, and biochemical inference to transcriptomics, metabolomics, functional enzymology, isotope-guided active-tissue identification, regulatory studies, and heterologous pathway reconstruction.
Mateo Peña-Morales, J. D. Vega-Páez, Natalie Cortes et al.· Plants· 0 citations
Nitrogen-containing heterocyclic compounds represent fundamental structural elements in contemporary medicinal chemistry. Pyrrolodiazepines, which result from the fusion of pyrrole and diazepine rings, integrate the beneficial properties of both parent structures and have emerged as a significant area of research in synthetic chemistry and pharmaceutical development in recent years. This review provides a systematic overview of the synthetic methodologies for pyrrolodiazepine derivatives that have been developed recently, encompassing transition-metal catalysis, cascade cyclization, multicomponent reactions, photoredox catalysis, base-mediated cyclization, and environmentally friendly synthesis approaches. The advantages and limitations of each method are critically evaluated. Furthermore, the biological activities of pyrrolodiazepines are extensively reviewed, addressing their antitumor, antibacterial, antiviral, central nervous system regulatory, metabolic, and cardiovascular effects, along with corresponding structure–activity relationship analyses. Finally, the review identifies the current challenges in the synthesis and application of pyrrolodiazepines and explores potential future development directions.
Mengyang Zhou, Shu-Tao Wang· Frontiers in Chemistry· 0 citations
Covering: 2005-2025Pyrrocidines and hirsutellones are a fascinating class of fungal natural products that possess an intricate chemical structure characterized by a distinctive macrocyclic ring fused to a decahydrofluorene core. Known for their complex architectures as PKS-NRPS hybrids, these metabolites are isolated from various fungi and have attracted significant attention due to their potent pharmacological properties, including antimicrobial, antifungal, and anticancer effects. This review article aims to shed light on the structural diversities of 52 fungal-derived pyrrocidines and hirsutellones reported over the period of 2005-2025, providing insights into their chemistry, biosynthetic origins, pharmacokinetic profiles, and structure-activity relationships (SARs). Furthermore, we critically evaluate their promising therapeutic potential, highlighting the opportunities they present for modern drug discovery and development.
M. Tammam, Islam El‐Awaad, A. Aouidate et al.· Natural product reports (Pri...· 0 citations
A comprehensive synthesis of recent progress and critical perspectives on unresolved questions offers an updated framework for understanding TA biosynthesis and supports future research in plant specialized metabolism, synthetic biology, and natural product engineering.
Shi-Yu Wan, Ya-Fei Zhang, Sheng-Yu Yang et al.· Molecules· 0 citations
Plants of the genus Alpinia, predominantly distributed across South Asia, have a long history of ethnomedicinal use for respiratory, gastrointestinal, and inflammatory conditions, with A. galanga widely utilized as a culinary flavoring. This review systematically compiles the relevant food technology applications of Alpinia phytocompounds, integrating recent research on their broader pharmacological potential. A semi-systematic, PRISMA-based literature synthesis was conducted across major scientific databases for peer-reviewed articles published between 2014 and 2026. Following rigorous screening, 160 studies were included out of 685 articles based on strict criteria requiring clear phytochemical identification, established biological activity, and defined food applications. Furthermore, in silico molecular docking analysis was performed using PyRx version 0.8 to correlate computational data with biological efficacy. Alpinia extracts exhibit significant potential as natural, clean-label food additives. Specifically, A. galanga demonstrates potent anti-browning properties and effectively extends the shelf life of highly perishable ready-to-eat meat products. Volatile oils and major isolated phytocompounds, notably 1,8-cineole and galangal, display robust inhibitory activities against foodborne pathogens. Additionally, in silico docking outcomes strongly align with in vitro profiles, validating their broader health-promoting attributes, including anti-microbial and anti-cancer properties. Alpinia phytocompounds serve as highly promising, sustainable alternatives to synthetic preservatives. However, their successful industrial integration will require advanced formulation strategies such as, nanoencapsulation, to overcome current limitations regarding sensory alteration in food matrices and to ensure comprehensive toxicological safety. By mitigating foodborne pathogens and preventing degradation, these extracts address critical industrial demands, offering immense value for functional food formulation alongside extensive pharmacological benefits.
