ReviewACS omega2026
The Epoxybenzooxocine Core of Integrastatins and Analogs: A Comprehensive Review of Structure, Synthetic Approaches, and Biological Applications.
Review in ACS omega, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Authors and funding
7 authors.
Funding
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Abstract
Integrastatins and their biogenetic counterparts possess a rare heterotetracyclic framework containing an unprecedented [6/6/6/6]-tetracyclic skeleton and a central [3/3/1]-bicyclic ketal core with high pharmaceutical potential, particularly due to their potent anti-HIV-1 integrase activity. Despite their promising scaffolds, a systematic consolidation of their chemistry and biology has been entirely lacking, creating a critical gap between the complex architecture of these natural polyketides and the targeted design of drug-like inhibitors. Herein, we present the first comprehensive review of this field, systematically analyzing 42 peer-reviewed publications from 1999 to 2025 retrieved from the Scopus, Web of Science, PubMed, and PubChem databases. Structural analysis confirms that while these rigid, nonplanar V-shaped molecules comply with Lipinski's Rule of Five as a baseline filter for drug-likeness, deeper ADMET profiling further highlights their high predicted human intestinal absorption (HIA) alongside a low risk of cardiotoxicity. Synthetically, we detail how the field has fundamentally evolved from an arduous 11-step sequence in 2003 to highly streamlined, atom-economical one-step protocols in 2008 and 2021, culminating in the 2025 total syntheses that successfully resolved long-standing structural misinterpretations of epicoccolide A and epicocconigrone A. Furthermore, a comparative assessment across eight critical synthetic parameters highlights the operational trade-offs between step efficiency, scalability, and functional group tolerance in current cascade cyclizations. Biologically, we evaluate the extensive
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Registered trials
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