Sydnone Ribosides as a Platform for the Synthesis of Pyrazole <i>C</i>-Nucleosides: A Unified Synthesis of Formycin B and Pyrazofurin

Bouton, Jakob; Calenbergh, Serge Van; Hullaert, Jan

doi:10.1021/acs.orglett.0c03523

Cited by 17 publications

(12 citation statements)

References 48 publications

(79 reference statements)

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“…Both PRF-A and FOR-A feature pyrazole-derived nucleobases, either imidazolopyrimidine (for PRF-A) or pyrazolopyrimidine (for FOR-A), which are obviously different from the typical nucleosides [ 50 ]. Recently, PRF-A and formycin B (a deaminated product of FOR-A) were synthesized with seven steps by employing a sydnone riboside as common intermediate [ 51 ].…”

Section: Biosynthesis Of the β-Rfap Synthase-like Type C -Nucleoside Moleculesmentioning

confidence: 99%

Biosynthesis of C-nucleoside antibiotics in actinobacteria: recent advances and future developments

et al. 2022

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Epidemic diseases and antibiotic resistance are urgent threats to global health, and human is confronted with an unprecedented dilemma to conquer them by expediting development of new natural product related drugs. C-nucleoside antibiotics, a remarkable group of microbial natural products with diverse biological activities, feature a heterocycle base linked with a ribosyl moiety via an unusual C-glycosidic bond, and have played significant roles in healthcare and for plant protection. Elucidating how nature biosynthesizes such a group of antibiotics has provided the basis for engineered biosynthesis as well as targeted genome mining of more C-nucleoside antibiotics towards improved properties. In this review, we mainly summarize the recent advances on the biosynthesis of C-nucleoside antibiotics, and we also tentatively discuss the future developments on rationally accessing C-nucleoside diversities in a more efficient and economical way via synthetic biology strategies.

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Section: Biosynthesis Of the β-Rfap Synthase-like Type C -Nucleoside Moleculesmentioning

confidence: 99%

Biosynthesis of C-nucleoside antibiotics in actinobacteria: recent advances and future developments

et al. 2022

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“…C-nucleosides and C-nucleotides are, of course, resistant to inactivation by hydrolysis of the sugar base linkage, in contrast with the more common C-N nucleotides [9]. Chemical synthesis of C-nucleosides uses two broad approaches: forming the heterocyclic nucleobase from an acyclic substituent attached to the sugar moiety or coupling a preformed heterocycle to the carbohydrate [10][11][12][13][14][15]. Both of these strategies often require the use of protecting groups, thereby increasing synthetic complexity.…”

Section: Introductionmentioning

confidence: 99%

Experimental and computational snapshots of C-C bond formation in a C-nucleoside synthase

Girt

Radadiya

et al. 2023

Open Biol.

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The biosynthetic enzyme, ForT, catalyses the formation of a C-C bond between 4-amino-1 H -pyrazoledicarboxylic acid and MgPRPP to produce a C-nucleoside precursor of formycin A. The transformation catalysed by ForT is of chemical interest because it is one of only a few examples in which C-C bond formation takes place via an electrophilic substitution of a small, aromatic heterocycle. In addition, ForT is capable of discriminating between the aminopyrazoledicarboxylic acid and an analogue in which the amine is replaced by a hydroxyl group; a remarkable feat given the steric and electronic similarities of the two molecules. Here we report biophysical measurements, structural biology and quantum chemical calculations that provide a detailed molecular picture of ForT-catalysed C-C bond formation and the conformational changes that are coupled to catalysis. Our findings set the scene for employing engineered ForT variants in the biocatalytic production of novel, anti-viral C-nucleoside and C-nucleotide analogues.

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“…[ 62 , 63 ] In the synthesis of other N ‐heterocycles, sydnones are often applied as reaction partners in the [3+2] dipolar cycloaddition. [ 48 , 64 , 65 ] Besides, the benzotriazole and sydnone scaffolds are central to a selection of active pharmaceutical ingredients (APIs) (Figure 3 c) and other industrially relevant materials (see below). As both N ‐heterocycles are slightly soluble in water, it will be beneficial to synthesize them in anhydrous media using a volatile nitrosating agent to avoid aqueous workup and extraction.…”

Section: Introductionmentioning

confidence: 99%

On Demand Flow Platform for the Generation of Anhydrous Dinitrogen Trioxide and Its Further Use inN‐Nitrosative Reactions

2022

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Dinitrogen trioxide (N 2 O 3 ) is a powerful and efficient nitrosating agent that comes with an unprecedented atom economy. However, the synthetic application of N 2 O 3 is still underdeveloped mostly due to its inherent instability and the lack of reliable protocols for its preparation. This paper presents an open-source setup and procedure for the on-demand generation of anhydrous N 2 O 3 solution (up to 1 M), which can be further used for reactions under batch and flow conditions. The accuracy and stability of N 2 O 3 concentration are guaranteed with the absence of head-space in the setup and with the synchronization of the gas flows. The reliability of this protocol is demonstrated by > 30 worked examples in the nitrosative synthesis of heterocycles-a library of structurally diverse benzotriazoles and sydnones. Kinetic and mechanistic aspects of the Nnitrosative steps are also explored.

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Sydnone Ribosides as a Platform for the Synthesis of Pyrazole C-Nucleosides: A Unified Synthesis of Formycin B and Pyrazofurin

Cited by 17 publications

References 48 publications

Biosynthesis of C-nucleoside antibiotics in actinobacteria: recent advances and future developments

Biosynthesis of C-nucleoside antibiotics in actinobacteria: recent advances and future developments

Experimental and computational snapshots of C-C bond formation in a C-nucleoside synthase

On Demand Flow Platform for the Generation of Anhydrous Dinitrogen Trioxide and Its Further Use inN‐Nitrosative Reactions

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