Isolation, chemistry, and biology of pyrrolo[1,4]benzodiazepine natural products

Abstract

The isolation of the antitumor antibiotic anthramycin in the 1960s prompted extensive research into pyrrolo [1,4]benzodiazepines (PBD) as potential therapeutics for the treatment of cancers. Since then, nearly 60 PBD natural products have been isolated and evaluated with regard to their biological activity. Synthetic studies and total syntheses have enabled access to PBD analogues, culminating in the development of highly potent anticancer agents. This review provides a summary of the occurrence and biological activity of PBD natural products and covers the strategies employed for their total syntheses.

Pyrrole-Containing Alkaloids from a Marine-Derived Actinobacterium Streptomyces zhaozhouensis and Their Antimicrobial and Cytotoxic Activities

“…Pyrroles possess a flat and electron-rich aromatic ring, and their structure is susceptible to electrophilic attack and can also interact with a variety of biomolecules via hydrogen bonds as well as π–π stacking interactions [ 19 ]. Because of their intriguing structures and wide range of biomedical properties, various pyrrole-based compounds have been studied for pharmacological activities [ 16 , 20 , 21 , 22 ]. Streptopyrroles are one of the examples of pyrrole-containing compounds with potent antimicrobial properties and inhibitory activity on the nitrogen regulator II (NRII) histidine kinase from Escherichia coli [ 23 ].…”

Stereoselective Olefination with Sterically Demanding Julia–Kocienski Reagents: Total Synthesis of Oxo-prothracarcin, Oxo-tomaymycin, and Boseongazepine B

“…Pyrrolo­[1,4]­benzodiazepines (PBD) are a class of naturally occurring anticancer antibiotics. , A characteristic structural feature of PBDs is the right-hand twisted three-ring system possessing electrophilic imine functionality at N10-C11 (Figure ) known to bind covalently to the minor groove of DNA via an exocyclic amino group of the guanine base. − As a consequence, interference with DNA repair, replication, transcription, and thus cell division is observed. Also, the N10-C11 amide group-possessing PBDs exhibit considerable cytotoxicity in various cancer cell lines acting as noncovalent binders .…”

Concise access to C2-ethylidene pyrrolo[1,4]benzodiazepine natural products

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A 3-step route toward pyrrolo [1,4]benzodiazepine (PBD) antitumor antibiotic class members oxo-prothracarcin and boseongazepine B has been developed. This methodology also enables preparing oxo-tomaymycin in only 4 linear steps representing the shortest total synthesis known to date.

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“…Pyrrolo [1,4]benzodiazepines (PBDs) are a broad class of anticancer antibiotics originating from naturally occurring microorganisms. 1 PBDs typically possess a right-hand twisted threering system with an (S)-configuration chiral center at the C11a position (Fig. 1).…”