Structural elucidation of A-74528, an inhibitor for 2′,5′-phosphodiesterase isolated from Streptomyces sp.

Fujita, Yöko; Kasuya, Atsushi; Matsushita, Yoh‐ichi; Suga, Miwa; Kizuka, Masaaki; Iijima, Yasuteru; Ogita, Takeshi

doi:10.1016/j.bmcl.2005.06.047

Cited by 14 publications

(9 citation statements)

References 12 publications

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“…We were pleased to find that photo-cycloaddition of the synthetically useful bicyclic building blocks Hajos–Parrish ketone ( 20 ) or Wieland–Miescher ketone ( 21 ), both of which contain an enone group at the ring junction, smoothly gave rise to the desired tetracyclic rings ( 39–42 ) in moderate yields (24–61%) under optimal conditions. The chemical structure of compound 39 and its relative configuration were determined by X-ray diffraction analysis: this compound has the core structure and stereochemistry of pleurotin ( 5 ) 5 , potentially making it a useful intermediate en route to this challenging molecule and its derivatives. Moreover, two steroids, 4-cholesten-3-one ( 22 ) and norandrostenedione ( 23 ), were selected as dienophiles in this PEDA reaction.…”

Section: Resultsmentioning

confidence: 99%

“…1 b), have been extensively studied as anticancer and antibiotic drugs. Interestingly, we also noticed a group of polyketides with all-carbon quaternary centers within the core anthracenols or anthraquinones, such as the newly isolated A-74528 ( 3 ) 5 , 6 and JBIR-85 ( 4 ) 7 , as well as the antibiotics pleurotin ( 5 ) 8 – 13 and oncocalyxone B ( 6 ) 14 , 15 . The additional quaternary carbons contribute to the diversity of these challenging chemical structures.…”

Section: Introductionmentioning

confidence: 93%

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Ti(Oi-Pr)4-promoted photoenolization Diels–Alder reaction to construct polycyclic rings and its synthetic applications

et al. 2017

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Stereoselective construction of polycyclic rings with all-carbon quaternary centers, and vicinal all-carbon quaternary stereocenters, remains a significant challenge in organic synthesis. These structures can be found in a wide range of polycyclic natural products and drug molecules. Here we report a Ti(Oi-Pr)4-promoted photoenolization/Diels–Alder (PEDA) reaction to construct hydroanthracenol and related polycyclic rings bearing all-carbon quaternary centers. This photolysis proceeds under mild conditions and generates a variety of photo-cycloaddition products in good reaction efficiency and stereoselectivity (48 examples), and has been successfully used in the construction of core skeleton of oncocalyxones, tetracycline and pleurotin. It also provides a reliable method for the late-stage modification of natural products bearing enone groups, such as steroids. The total synthesis of oncocalyxone B was successfully achieved using this PEDA approach.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 93%

Ti(Oi-Pr)4-promoted photoenolization Diels–Alder reaction to construct polycyclic rings and its synthetic applications

et al. 2017

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“…discovered during the screening for 2 0 ,5 0 -oligoadenylate phosphodiesterase inhibitors. 62 The planar structure of A-74528 was principally elucidated by…”

Section: F I G U R E 3 (Continued)mentioning

confidence: 99%

Application of INADEQUATE NMR techniques for directly tracing out the carbon skeleton of a natural product

Ismail

Nahar

Sarker

2020

Phytochemical Analysis

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Introduction Nuclear magnetic resonance (NMR) measurement of 1JCC coupling by two‐dimensional (2D) INADEQUATE (incredible natural abundance double quantum transfer experiment), which is a special case of double‐quantum (DQ) spectroscopy that offers unambiguous determination of 13C–13C spin–spin connectivities through the DQ transitions of the spin system, is especially suited to solving structures rich in quaternary carbons and poor in hydrogen content (Crews rule). Objective To review published literature on the application of NMR methods to determine structure in the liquid‐state, which specifically considers the interaction of a pair of carbon‐13 (13C) nuclei adjacent to one another, to allow direct tracing out of contiguous carbon connectivity using 2D INADEQUATE. Methodology A comprehensive literature search was implemented with various databases: Web of Knowledge, PubMed and SciFinder, and other relevant published materials including published monographs. The keywords used, in various combinations, with INADEQUATE being present in all combinations, in the search were 2D NMR, 1JCC coupling, natural product, structure elucidation, 13C–13C connectivity, cryoprobe and CASE (computer‐assisted structure elucidation)/PANACEA (protons and nitrogen and carbon et alia). Results The 2D INADEQUATE continues to solve “intractable” problems in natural product chemistry, and using milligram quantities with cryoprobe techniques combined with CASE/PANACEA experiments can increase machine time efficiency. The 13C–13C‐based structural elucidation by dissolution single‐scan dynamic nuclear polarisation NMR can overcome disadvantages of 13C insensitivity at natural abundance. Selected examples have demonstrated the trajectory of INADEQUATE spectroscopy from structural determination to clarification of metabolomics analysis and use of DFT (density functional theory) and coupling constants to clarify the connectivity, hybridisation and stereochemistry within natural products. Conclusions Somewhat neglected over the years because of perceived lack of sensitivity, the 2D INADEQUATE NMR technique has re‐emerged as a useful tool for solving natural products structures, which are rich in quaternary carbons and poor in hydrogen content.

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“…SANK 61196, discovered by Ogita and coworkers during the screening of microbial extracts for antiviral compounds that activate the interferon (INF) system via 2′,5′-oligoadenylate phosphodiesterase (2′-PDE) inhibition 1,2. Viral infection of cells induces the production of INFs, which in turn up-regulates 2′,5′-oligoadenylates (2–5A) 3.…”

Section: Introductionmentioning

confidence: 99%

Cloning, Sequencing, Heterologous Expression, and Mechanistic Analysis of A-74528 Biosynthesis

et al. 2010

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A-74528 is a recently discovered natural product of Streptomyces sp. SANK 61196 that inhibits 2′, 5′-oligoadenylate phosphodiesterase (2′-PDE), a key regulatory enzyme of the interferon pathway. Inhibition of 2′-PDE by A-74528 reduces viral replication, and therefore shows promise as a new type of antiviral drug. The complete A-74528 gene cluster, comprising of 29 open reading frames, was cloned and sequenced, and shown to possess a type II polyketide synthase (PKS) at its core. Its identity was confirmed by analysis of a mutant generated by targeted disruption of a PKS gene, and by functional expression in a heterologous Streptomyces host. Remarkably, it showed exceptional end-to-end sequence identity to the gene cluster responsible for biosynthesis of fredericamycin A, a structurally unrelated antitumor antibiotic with a distinct mode of action. Whereas the fredericamycin producing strain, Streptomyces griseus, produced undetectable quantities of A-74528, the A-74528 gene cluster was capable of producing both antibiotics. The biosynthetic roles of three genes, including one that represents the only qualitative difference between the two gene clusters, were investigated by targeted gene disruption. The implications for the evolution of antibiotics with different biological activities from the same gene cluster are discussed.

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Structural elucidation of A-74528, an inhibitor for 2′,5′-phosphodiesterase isolated from Streptomyces sp.

Cited by 14 publications

References 12 publications

Ti(Oi-Pr)4-promoted photoenolization Diels–Alder reaction to construct polycyclic rings and its synthetic applications

Ti(Oi-Pr)4-promoted photoenolization Diels–Alder reaction to construct polycyclic rings and its synthetic applications

Application of INADEQUATE NMR techniques for directly tracing out the carbon skeleton of a natural product

Cloning, Sequencing, Heterologous Expression, and Mechanistic Analysis of A-74528 Biosynthesis

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