Total synthesis of (±)-naphthacemycin A9, possessing both antibacterial activity against methicillin-resistant Staphylococcus aureus and circumventing effect of β-lactam resistance

Hirose, Tomoyasu; Kojima, Yasuhiro; Matsui, Hidehito; Hanaki, Hideaki; Iwatsuki, Masato; Shiomi, Kazuro; Ōmura, Satoshi; Sunazuka, Toshiaki

doi:10.1038/ja.2016.141

Cited by 24 publications

(24 citation statements)

References 41 publications

(66 reference statements)

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“…The gem -dimethyl tetracyclic carbon framework in these compounds has been reported to show potent anti-methicillin-resistant Staphylococcus aureus (MRSA) activities. Furthermore, fasamycins A and B were found to inhibit the FabF enzyme of type II fatty acid (FASII) biosynthesis in bacteria [4], while naphthacemycins showed inhibition against several MRSA and methicillin-susceptible Staphylococcus aureus (MSSA) strains, in addition to an efficient circumvention of β-lactam resistance when administered in combination with imipenem [5,6,7]. As part of our ongoing screening program to search for unique scaffolds, we have identified a cluster of metabolites containing the rare phenylnaphthacene carbon framework from the soil bacterium, Streptomyces sp.…”

Section: Introductionmentioning

confidence: 99%

Accramycin A, A New Aromatic Polyketide, from the Soil Bacterium, Streptomyces sp. MA37

et al. 2019

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Drug-like molecules are known to contain many different building blocks with great potential as pharmacophores for drug discovery. The continued search for unique scaffolds in our laboratory led to the isolation of a novel Ghanaian soil bacterium, Streptomyces sp. MA37. This strain produces many bioactive molecules, most of which belong to carbazoles, pyrrolizidines, and fluorinated metabolites. Further probing of the metabolites of MA37 has led to the discovery of a new naphthacene-type aromatic natural product, which we have named accramycin A 1. This molecule was isolated using an HPLC-photodiode array (PDA) guided isolation process and MS/MS molecular networking. The structure of 1 was characterized by detailed analysis of LC-MS, UV, 1D, and 2D NMR data. Preliminary studies on the antibacterial properties of 1 using Group B Streptococcus (GBS) produced a minimum inhibitory concentration (MIC) of 27 µg/mL. This represents the first report of such bioactivity amongst the naphthacene-type aromatic polyketides, and also suggests the possibility for the further development of potent molecules against GBS based on the accramycin scaffold. A putative acc biosynthetic pathway for accramycin, featuring a tridecaketide-specific type II polyketide synthase, was proposed.

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Section: Introductionmentioning

confidence: 99%

Accramycin A, A New Aromatic Polyketide, from the Soil Bacterium, Streptomyces sp. MA37

et al. 2019

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“…Scheme 24 Hong's synthesis of the medermycin core structure 3.14 Total Synthesis of (±)-Naphthacemycin A 9 (24) 66 Naphthacemycin A 9 (24) is a member of a series of new antibiotics isolated by Ōmura et al from the culture broth of Streptomyces sp. KB-3346-5.…”

Section: Account Syn Lettmentioning

confidence: 99%

“…The total synthesis of (±)-naphthacemycin A 9 (24) by Ōmura et al is depicted in Scheme 25. 66 The Fischer carbene 136 was prepared in three steps from 135 and then reacted with the alkyne 137 under microwave irradiation to give the phenol, which on methylation provided 139 as the minor product. The major product was the cyclobutenone 138.…”

Section: Account Syn Lettmentioning

confidence: 99%

A Decade with Dötz Benzannulation in the Synthesis of Natural Products

Fernandes

Kumari²,

Pathare

2020

Synlett

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The Dötz benzannulation is a named reaction that utilizes Fischer chromium carbenes in a formal [3+2+1] cycloaddition with an alkyne and CO to produce the corresponding benzannulated product. Since its development in the 1970s, this reaction has been extensively used in the synthesis of natural products and various molecular architectures. Although the reaction sometimes suffers from the formation of other competing side products, the rapid construction of naphthol structures with a 1,4-dihydroxy unit makes it the most appropriate reaction for the synthesis of p-naphthoquinones. This review focuses on our group’s efforts over the past decade on the extensive use of this annulation reaction along with the contributions of others on the synthesis of different natural products.1 Introduction2 General Description and Mechanism of the Dötz Benzannulation Reaction3 Applications of the Dötz Benzannulation in Natural Product Synthesis over the Last Decade4 Conclusion

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“…As can be seen by the inspection of the Scheme , Hirose and co‐workers utilized the Dötz reaction between the Fischer carbene complex 255 and alkyne partner 256 as a key transformation to produce the methyl‐naphthacemycin A 9 ( 261) which on demethylation in the presence of CeCl 3 and NaI afforded the target molecule 262 …”

Section: Synthesis Of Natural Productsmentioning

confidence: 99%

The Dötz Benzannulation Reaction: A Booming Methodology for Natural Product Synthesis

2020

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Since its finding in 1975, the Dötz benzannulation reaction has attracted a great attention of the scientific community as it permits the regio‐controlled construction of functionalised aromatic frameworks from acyclic precursors. In recent years, this beautifully simple yet much powerful technique for the formation of C−C bonds has opened‐up new possibilities in modern synthetic organic chemistry. In this Review, we report the developments in natural products synthesis by employing the Dötz benzannulation as a key transformation. Although, a flow of publications have witnessed a constant progress in this wonderful area of research, but to our best knowledge this is the first review which purely focuses on the applications of the Dötz benzannulation reaction in natural product synthesis. We are assured that this review will act as a promoter in amplifying the applications of the Dötz benzannulation in the domain of synthetic organic chemistry.

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Total synthesis of (±)-naphthacemycin A9, possessing both antibacterial activity against methicillin-resistant Staphylococcus aureus and circumventing effect of β-lactam resistance

Cited by 24 publications

References 41 publications

Accramycin A, A New Aromatic Polyketide, from the Soil Bacterium, Streptomyces sp. MA37

Accramycin A, A New Aromatic Polyketide, from the Soil Bacterium, Streptomyces sp. MA37

A Decade with Dötz Benzannulation in the Synthesis of Natural Products

The Dötz Benzannulation Reaction: A Booming Methodology for Natural Product Synthesis

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