488-04-0

Basic information

• Product Name: holomycin
• Synonyms: holomycin;N-(4,5-Dihydro-5-oxo-1,2-dithiolo[4,3-b]pyrrol-6-yl)acetamide;N-Demethylthiolutin;N-(5-oxo-4H-dithiolo[4,3-b]pyrrol-6-yl)acetamide
• CAS NO: 488-04-0
• Molecular Formula: C₇H₆N₂O₂S₂
• Molecular Weight: 214.268
• Mol File: 488-04-0.mol
• Article Data: 6

Chemical Properties

• Melting Point: 268 °C (decomp)
• Boiling Point: 532.1°Cat760mmHg
• Flash Point: 275.6°C
• Appearance: /
• Density: 1.63g/cm³
• Vapor Pressure: 0mmHg at 25°C
• Refractive Index: 1.742
• PKA: 9.33±0.40(Predicted)
• CAS DataBase Reference: holomycin(CAS DataBase Reference)
• NIST Chemistry Reference: holomycin(488-04-0)
• EPA Substance Registry System: holomycin(488-04-0)

Safety Data

• Hazardous Substances Data: 488-04-0(Hazardous Substances Data)

Usage

Synthesis Reference(s)

Journal of the American Chemical Society, 86, p. 5654, 1964 DOI: 10.1021/ja01078a049

InChI:InChI=1/C7H6N2O2S2/c1-3(10)8-5-6-4(2-12-13-6)9-7(5)11/h2H,1H3,(H,8,10)(H,9,11)

Upstream product

• 64-19-7 acetic acid 
• 62698-43-5 7-methanesulfonyloxy-2-(4-methoxy-phenyl)-2-methyl-6-oxo-5,6-dihydro-[1,3]dithiino[5,4-b]pyrrole-4-carboxylic acid methyl ester 
• 62698-45-7 6-(4-methoxy-benzylamino)-5-oxo-4,5-dihydro-[1,2]dithiolo[4,3-b]pyrrole-3-carboxylic acid methyl ester 
• 62698-42-4 2-(4-methoxy-phenyl)-2-methyl-6,7-dioxo-5,6,7,7a-tetrahydro-[1,3]dithiino[5,4-b]pyrrole-4-carboxylic acid methyl ester 
• 90993-81-0 6-amino-4H-[1,2]dithiolo[4,3-b]pyrrol-5-one hydrochloride 
• 75-36-5 acetyl chloride 
• 62698-47-9 6-acetylamino-5-oxo-4,5-dihydro-[1,2]dithiolo[4,3-b]pyrrole-3-carboxylic acid methyl ester 
• 62698-44-6 7-(4-methoxy-benzylamino)-2-(4-methoxy-phenyl)-2-methyl-6-oxo-5,6-dihydro-[1,3]dithiino[5,4-b]pyrrole-4-carboxylic acid methyl ester 

Downstream Products

• 488-03-9 6-amino-4H-[1,2]dithiolo[4,3-b]pyrrol-5-one 

Relevant articles and documents

Inhibition of Isoleucyl-tRNA Synthetase by the Hybrid Antibiotic Thiomarinol

Hybrid antibiotics are an emerging antimicrobial strategy to overcome antibiotic resistance. The natural product thiomarinol A is a hybrid of two antibiotics: holothin, a dithiolopyrrolone (DTP), and marinolic acid, a close analogue of the drug mupirocin that is used to treat methicillin-resistant Staphylococcus aureus (MRSA). DTPs disrupt metal homeostasis by chelating metal ions in cells, whereas mupirocin targets the essential enzyme isoleucyl-tRNA synthetase (IleRS). Thiomarinol A is over 100-fold more potent than mupirocin against mupirocin-sensitive MRSA; however, its mode of action has been unknown. We show that thiomarinol A targets IleRS. A knockdown of the IleRS-encoding gene, ileS, exhibited sensitivity to a synthetic analogue of thiomarinol A in a chemical genomics screen. Thiomarinol A inhibits MRSA IleRS with a picomolar Ki and binds to IleRS with low femtomolar affinity, 1600 times more tightly than mupirocin. We find that thiomarinol A remains effective against high-level mupirocin-resistant MRSA and provide evidence to support a dual mode of action for thiomarinol A that may include both IleRS inhibition and metal chelation. We demonstrate that MRSA develops resistance to thiomarinol A to a substantially lesser degree than mupirocin and the potent activity of thiomarinol A requires hybridity between DTP and mupirocin. Our findings identify a mode of action of a natural hybrid antibiotic and demonstrate the potential of hybrid antibiotics to combat antibiotic resistance.

Thiomarinol, a new hybrid antimicrobial antibiotic produced by a marine bacterium. Fermentation, isolation, structure, and antimicrobial activity

Thiomarinol, an antimicrobial antibiotic, was isolated from the culture broth of a marine bacterium, Alteromonas rava sp. nov. SANK 73390. Its structure was deduced as a hybrid composed of a pseudomonic acid analogue and holothin by NMR spectral analysis and chemical degradation. Antimicrobial activity against Gram-positive and Gram-negative bacteria of thiomarinol was stronger than both of pseudomonic acids and pyrrothine antibiotics.

Synthesis of holomycin and derivatives

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