Optimized and Scalable Synthesis of Carba‐α‐<scp>d</scp>‐Glucosamine

Babczyk, Alexander; Wingen, Lukas M.; Menche, Dirk

doi:10.1002/ejoc.202001203

Cited by 3 publications

(3 citation statements)

References 32 publications

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“…In the following four decades, the chemical, biological, and conformational aspects of carbasugars were extensively studied [12,13], resulting in studies on enzyme inhibition, lectin-binding, and even HIV and cancer treatment [14][15][16]. Various strategies have been employed for the synthesis and isolation of carbasugars, mostly starting from simple monosaccharides such as glucosamine and resulting in the corresponding carbasugars [17][18][19]. Other approaches work from simple hexopyranoses to more complex carbafuranoses such as carbaarabinofuranosides [20,21] or even more complex carbasugar derivatives such as fluorinated carbasugars [22].…”

Section: Introductionmentioning

confidence: 99%

“…Various strategies have been employed for the synthesis and isolation of carbasugars, mostly starting from simple monosaccharides such as glucosamine and resulting in the corresponding carbasugars [ 17 – 19 ]. Other approaches work from simple hexopyranoses to more complex carbafuranoses such as carbaarabinofuranosides [ 20 , 21 ] or even more complex carbasugar derivatives such as fluorinated carbasugars [ 22 ].…”

Section: Introductionmentioning

confidence: 99%

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Current Synthetic Approaches to the Synthesis of Carbasugars from Non-Carbohydrate Sources

et al. 2022

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Carbasugars are a group of carbohydrate derivatives in which the ring oxygen is replaced by a methylene group, producing a molecule with a nearly identical structure but highly different behavior. Over time, this definition has been extended to include other unsaturated cyclohexenols and carba-, di-, and polysaccharides. Such molecules can be found in bacterial strains and the human body, acting as neurotransmitters (e.g., inositol trisphosphate). In science, there are a wide range of research areas that are affected by, and involve, carbasugars, such as studies on enzyme inhibition, lectin-binding, and even HIV and cancer treatment. In this review article, different methods for synthesizing carbasugars, their derivatives, and similar cyclohexanes presenting comparable characteristics are summarized and evaluated, utilizing diverse starting materials and synthetic procedures.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Current Synthetic Approaches to the Synthesis of Carbasugars from Non-Carbohydrate Sources

et al. 2022

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“…1 Recently, an efficient, highyielding synthesis of α-D-carba-glucosamine (CGlcN) was reported that allowed the biological evaluations of its mode of action as an glucosamine analog. [2][3][4][5] In B. subtilis, CGlcN is taken up and concomitantly phosphorylated, like the natural metabolite, via the glucosamine-specific PTS system GamP, gaining intracellularly CGlcN-6-phosphate (CGlcN6P). 3 Due to impaired acetal chemistry CGlcN6P cannot be deamidated via the glucosamine deamidase (NagB) such as the carbohydrate counterpart glucosamine-6-phosphate (GlcN6P).…”

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confidence: 99%

Metabolization of α-D-carba-glucosamine in vivo generates antimetabolites of cell wall precursors

Mund

Friz

Esser

et al. 2023

Preprint

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α-D-Carba-glucosamine (CGlcN) is a carbocyclic analog of alpha-D-glucosamine that inhibits growth of Bacillus subtilis and Staphylococcus aureus. CGlcN is internalized and concomitantly phosphorylated via the phosphotransferase system yielding alpha;-carba-glucosamine-6-phosphate (CGlcN6P), which interferes with expression of the glutamine-fructose-6-phosphate amidotransferase (GlmS; glucosamine synthase) by activating the glmS riboswitch. Herein, we report that CGlcN6P is efficiently metabolized to carbasugar nucleotides along the peptidoglycan biosynthetic route. Mass spectrometric analysis confirmed the occurrence of carbocyclic peptidoglycan nucleotides UDP-carba-D-N-acetyl-glucosamine (UDP-CGlcNAc) and UDP-carba-D-N-acetylmuramic acid-pentapeptide (UDP-CMurNAc-5P) in the presence of CGlcN and revealed accumulation of these carba-metabolites upon antibiotic treatment interfering with biosynthetic enzyme functions. Thus, carbocyclic carbohydrates and nucleotide analogs are generated by the promiscuous bacterial cell wall biosynthetic enzymes and act as antimetabolites, causing bacterial growth inhibition by interference with cell wall synthesis. Our findings reveal CGlcN not only as putative antibiotic molecule with previously unknown antimetabolite mode of action, but also as tool to study the bacterial cell wall metabolism, e.g., in synergy with other antibiotics.

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Carba‐Sugar Analogs of Glucosamine‐6‐Phosphate: New Activators for the glmS Riboswitch

Stängle

Silkenath

Gehle

et al. 2022

Chemistry A European J

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Riboswitches are 5’‐untranslated mRNA regions mostly found in bacteria. They are promising drug targets to overcome emerging bacterial resistance against commonly used antibiotics. The glmS riboswitch is unique among the family of riboswitches as it is a ribozyme that undergoes self‐cleavage upon binding to glucosamine‐6‐phosphate (GlcN6P). Previously, we showed that carba glucosamine‐6‐phosphate (carba‐GlcN6P) induces self‐cleavage of the riboswitch with a potency similar to that of GlcN6P. Here, we report a synthetic approach to a new class of carba‐GlcN6P derivatives with an alkoxy substituent in the carba position. Key features of the synthesis are a ring closing metathesis followed by a hydroboration. The strategy gives access to libraries of carba‐GlcN6P derivatives. Ribozyme cleavage assays unraveled new activators for the glmS riboswitch from Listeria monocytogenes and Clostridium difficile.

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Optimized and Scalable Synthesis of Carba‐α‐d‐Glucosamine

Cited by 3 publications

References 32 publications

Current Synthetic Approaches to the Synthesis of Carbasugars from Non-Carbohydrate Sources

Current Synthetic Approaches to the Synthesis of Carbasugars from Non-Carbohydrate Sources

Metabolization of α-D-carba-glucosamine in vivo generates antimetabolites of cell wall precursors

Carba‐Sugar Analogs of Glucosamine‐6‐Phosphate: New Activators for the glmS Riboswitch

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