Pestalone

Studies toward Pestalachloride B: Synthesis of the 6/7/6 Tricyclic Scaffold.[Pubmed:41709707]

Org Lett. 2026 Mar 6;28(9):2831-2835.

Antibiotic therapy is a critical part of modern healthcare, and the discovery of antibiotics with novel mechanisms of action is needed to combat the rise of antimicrobial resistance. Pestalachloride B, isolated from Pestalotiopsis adusta, is a compound belonging to the Pestalone family of natural products which demonstrates potent and selective antimicrobial activity against clinically relevant, antimicrobial-resistant Gram-positive bacteria. Here, we report the first synthetic studies focused specifically on pestalachloride B. Two key disconnections were evaluated for the construction of the rare 6/7/6 tricyclic scaffold, and a key intramolecular Parham-type cyclization was found to afford the desired scaffold in 74% yield, enabling us to obtain a late-stage intermediate bearing the complete pestalachloride B framework in 8% overall yield over 11 steps.

Synergistic effect of secondary metabolites isolated from Pestalotiopsis sp. FKR-0115 in overcoming beta-lactam resistance in MRSA.[Pubmed:37302827]

J Gen Appl Microbiol. 2024 Feb 2;69(4):234-238.

Six aromatic secondary metabolites, Pestalone (1), emodin (2), phomopsilactone (3), pestalachlorides B (4), C (5), and D (6), were isolated from Pestalotiopsis sp. FKR-0115, a filamentous fungus collected from white moulds growing on dead branches in Minami Daito Island. The efficacy of these secondary metabolites against methicillin-resistant Staphylococcus aureus (MRSA) with and without meropenem (beta-lactam antibiotic) was evaluated using the paper disc method and broth microdilution method. The chemical structures of the isolated compounds (1-6) were characterised using spectroscopic methods, including nuclear magnetic resonance and mass spectrometry. All six isolated compounds exhibited synergistic activity with meropenem against MRSA. Among the six secondary metabolites, Pestalone (1) overcame bacterial resistance in MRSA to the greatest extent.

Pestalotinones A-D, new benzophenone antibiotics from endophytic fungus Pestalotiopsis trachicarpicola SC-J551.[Pubmed:35115699]

J Antibiot (Tokyo). 2022 Apr;75(4):207-212.

Four new Pestalone-type benzophenones, pestalotinones A-D (1-4), along with six known congeners, Pestalone, Pestalone E-F, SB87-Cl, SB87-H, and pestalachloride B, were isolated from the endophytic fungus Pestalotiopsis trachicarpicola SC-J551 cultivated on rice grains. Their structures were established by extensive spectroscopic analysis. Compounds 1-3 exhibited potent activity against Staphylococcus aureus and MRSA (MIC: 1.25-2.5 mug ml(-1)) while no cytotoxicity against Vero cells (IC(50) > 50 muM). The activity profile of this group of compounds suggested that replacement of the C-14 aldehyde with an oxymethyl greatly increases their activity and selectivity towards the bacteria and chlorine substitutions result in the increase of antibacterial activity and slight decrease of cytotoxicity against the mammalian cells.

On the antibiotic and antifungal activity of pestalone, pestalachloride A, and structurally related compounds.[Pubmed:23905700]

J Nat Prod. 2013 Aug 23;76(8):1519-22.

Pestalone (1) is a prominent marine natural product first isolated by M. Cueto et al. in 2001 from a co-fermentation of a marine fungus with a marine bacterium. For more than 10 years, 1 had been considered as a promising new antibiotic compound, the reported MIC against methicillin-resistant Staphylococcus aureus (MRSA) being 37 ng/mL. After overcoming the limited availability of 1 by total synthesis (N. Slavov et al., 2010) we performed new biological tests, which did not confirm the expected degree of antibiotic activity. The observed activity of Pestalone against different MRSA strains was 3-10 mug/mL, as determined independently in two laboratories. A number of synthetic derivatives of 1 including pestalachloride A and other isoindolinones (formed from 1 by reaction with amines) did not exhibit higher activities as compared to 1 against MRSA and a series of plant pathogens.

Nucleophile- or light-induced synthesis of 3-substituted phthalides from 2-formylarylketones.[Pubmed:22519905]

Org Lett. 2012 May 4;14(9):2338-41.

The surprisingly facile conversion (isomerization) of 2-formyl-arylketones into 3-substituted phthalides, as observed for the marine natural product Pestalone and its per-O-methylated derivative, was investigated using a series of simple 2-acylbenzaldehydes as substrates. The transformation generally proceeds smoothly in DMSO, either in a Cannizarro-Tishchenko-type reaction under nucleophile catalysis (NaCN) or under photochemical conditions (DMSO, 350 nm).

N-Capping of primary amines with 2-acyl-benzaldehydes to give isoindolinones.[Pubmed:21902238]

Org Lett. 2011 Oct 7;13(19):5374-7.

A unique reactivity pattern, first observed in the conversion of the marine natural product Pestalone into pestalachloride A, was investigated. It was shown that 2-formyl-arylketones smoothly react with ammonia and primary amines, respectively, under mild conditions to afford 3-substituted isoindolinones in high yield. The reaction represents a new option for the derivatization (N-capping) of primary amines. As the substrates are readily accessible the methodology opens a short and modular access to pharmaceutically relevant substituted isoindolinones.

Small-molecule elicitation of microbial secondary metabolites.[Pubmed:21375710]

Microb Biotechnol. 2011 Jul;4(4):471-8.

Microbial natural products continue to be an unparalleled resource for pharmaceutical lead discovery, but the rediscovery rate is high. Bacterial and fungal sequencing studies indicate that the biosynthetic potential of many strains is much greater than that observed by fermentation. Prodding the expression of such silent (cryptic) pathways will allow us to maximize the chemical diversity available from microorganisms. Cryptic metabolic pathways can be accessed in the laboratory using molecular or cultivation-based approaches. A targeted approach related to cultivation-based methods is the application of small-molecule elicitors to specifically affect transcription of secondary metabolite gene clusters. With the isolation of the novel secondary metabolites lunalides A and B, oxylipins, cladochromes F and G, nygerone A, chaetoglobosin-542, -540 and -510, sphaerolone, dihydrosphaerolone, mutolide and Pestalone, and the enhanced production of known secondary metabolites like penicillin and bacitracin, chemical elicitation is proving to be an effective way to augment natural product libraries.

Pestalone, a new antibiotic produced by a marine fungus in response to bacterial challenge.[Pubmed:11720529]

J Nat Prod. 2001 Nov;64(11):1444-6.

The isolation and structure determination of a new chlorinated benzophenone antibiotic, Pestalone (1), is described. The new compound was produced by a cultured marine fungus only when a unicellular marine bacterium, strain CNJ-328, was co-cultured in the fungal fermentation. The fungus, isolated from the surface of the brown alga Rosenvingea sp. collected in the Bahamas Islands, was identified as an undescribed member of the genus Pestalotia. The structure of 1, initially assigned with only modest confidence by combined spectral and chemical data, was confirmed by single-crystal X-ray analysis. Pestalone (1) exhibits moderate in vitro cytotoxicity in the National Cancer Institute's 60 human tumor cell line screen (mean GI(50) = 6.0 microM). More importantly, Pestalone shows potent antibiotic activity against methicillin-resistant Staphylococcus aureus (MIC = 37 ng/mL) and vancomycin-resistant Enterococcus faecium (MIC = 78 ng/mL), indicating that Pestalone should be evaluated in advanced models of infectious disease.

Pestalone (CAS 381722-85-6) is a natural product offered by BioCrick for research applications. Customers can buy or order Pestalone from BioCrick, a supplier and manufacturer of research chemicals, with product specifications, purity, packaging, and pricing information available upon request.