d-Glucose- and d-mannose-based antimetabolites. Part 2. Facile synthesis of 2-deoxy-2-halo-d-glucoses and -d-mannoses

Fokt, Izabela; Szymański, Sławomir; Skóra, Stanisław; Cybulski, Marcin; Madden, Timothy; Priebe, Waldemar

doi:10.1016/j.carres.2009.06.016

Cited by 23 publications

(18 citation statements)

References 37 publications

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“…In fact, the non-radioactive analog of radiopharmaceutical agent FDG, 2-fluoro-2-deoxy-D-glucose ( 25 ), was found to be more potent than 2-DG in killing hypoxic cells among a series of 2-halo-D-glucose analogs, comprising 2-chloro- ( 26 ) and 2-bromo-2-deoxy-D-glucose ( 27 ), which were realized in an attempt to improve the activity of their non-halogenated progenitor 2-DG. [112] The binding affinities of these derivatives for HK decrease as the size of the halogen increases: fluoro ( 25 )>chloro ( 26 )>bromo ( 27 ). Molecular modeling studies demonstrated that this is due to the fact that the increasing size of the halogens generates steric clashes that destabilize the binding with the enzyme active site.…”

Section: Glycolytic Effectors As Potential Targets In Cancer Therapymentioning

confidence: 99%

Anticancer Agents That Counteract Tumor Glycolysis

2012

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Can we consider cancer as a “metabolic disease”? Tumors are the result of a metabolic selection, forming tissues composed of heterogeneous cells that generally express an overactive metabolism as a common feature. In fact, cancer cells have to deal with increased needs for both energy and biosynthetic intermediates, in order to support their growth and invasiveness. However, their high proliferation rate often generates regions that are not sufficiently oxygenated. Therefore, their carbohydrate metabolism has to rely mostly on a glycolytic process that is uncoupled from oxidative phosphorylation. This metabolic switch, also known as the “Warburg Effect”, constitutes a fundamental adaptation of the tumor cells to a relatively hostile environment, and supports the evolution of aggressive and metastatic phenotypes. As a result, tumor glycolysis may constitute an attractive target for cancer therapy. This approach has often raised concerns that anti-glycolytic agents may cause serious side effects on normal cells. Actually, the key for a selective action against cancer cells can be found in their hyperbolic addiction to glycolysis, which may be exploited to generate new anti-cancer drugs showing minimal toxicity. In fact, there is growing evidence that supports many glycolytic enzymes and transporters as suitable candidate targets for cancer therapy. Herein we review some of the most relevant anti-glycolytic agents that have been investigated so far for the treatment of cancer.

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Section: Glycolytic Effectors As Potential Targets In Cancer Therapymentioning

confidence: 99%

Anticancer Agents That Counteract Tumor Glycolysis

2012

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“…[1,2] Also, fluorinated carbohydrates have found their use among others as biocompatible surfactants, [3,4] mechanistic probes, [5][6][7] positron-emitting radiopharmaceuticals, [8,9] potential anticancer agents, [10][11][12][13] and building blocks for other bioactive compounds. [14][15][16] As compared to their natural derivatives, fluorinated carbohydrates have altered hydrogen bonding Benzoylated Deoxyfluoropyranosides 349 abilities and metabolic stability.…”

Section: Introductionmentioning

confidence: 99%

Synthesis and Structure Elucidation of Benzoylated Deoxyfluoropyranosides

Esmurziev

Simić

Hoff

et al. 2010

Journal of Carbohydrate Chemistry

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Benzoylated deoxyfluoropyranosides have been synthesized, starting with protected, unprotected, or fluorinated precursors. Fluorination of eight derivatives was compared using DAST and Deoxo-Fluor as reagents. Deoxo-Fluor was found to be especially useful in the fluorination of methyl 2,3,4-O-tribenzoyl α-D-mannopyranoside and β-D-glucopyranoside, resulting in better yields and avoiding the 1,6-methoxy migration experienced with DAST for one derivative. The two reagents gave comparable yields in the fluorination of other methyl pyranosides, confirming Deoxo-Fluor as a safer alternative to DAST. Methyl α-D-mannopyranoside underwent fluorination to yield the 4,6-difluorotalopyranoside and the corresponding cyclic sulfite. The NMR spectroscopic properties of 11 benzoyl deoxy-fluoropyranosides are reported.

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“…Accordingly, treatment of diacetylrhamnal 15 with SelectFluor in aqueous acetonitrile followed by acetylation with acetic anhydride in pyridine during the workup caused electrophilic fluorination to give a mixture of the four sugar triacetates 46 α/β and 47 (Scheme ) with little stereoselectivity. One of the four triacetates, the β‐fluoro‐rhamnose 46 β , was isolated as a pure crystalline solid.…”

Section: Resultsmentioning

confidence: 99%

6‐Deoxyhexoses from l‐Rhamnose in the Search for Inducers of the Rhamnose Operon: Synergy of Chemistry and Biotechnology

Liu

Yoshihara

Kelly

et al. 2016

Chemistry A European J

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In the search for alternative non-metabolizable inducers in the L-rhamnose promoter system, the synthesis of fifteen 6-deoxyhexoses from L-rhamnose demonstrates the value of synergy between biotechnology and chemistry. The readily available 2,3-acetonide of rhamnonolactone allows inversion of configuration at C4 and/or C5 of rhamnose to give 6-deoxy-D-allose, 6-deoxy-D-gulose and 6-deoxy-L-talose. Highly crystalline 3,5-benzylidene rhamnonolactone gives easy access to Lquinovose [6-deoxy-L-glucose], L-olivose and rhamnose analogue with C2 azido, amino and acetamido substituents. Electrophilic fluorination of rhamnal gives a mixture of 2-deoxy-2-fluoro-Lrhamnose and 2-deoxy-2-fluoro-L-quinovose. Biotechnology provides access to 6-deoxy-L-altrose and 1-deoxy-L-fructose.

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d-Glucose- and d-mannose-based antimetabolites. Part 2. Facile synthesis of 2-deoxy-2-halo-d-glucoses and -d-mannoses

Cited by 23 publications

References 37 publications

Anticancer Agents That Counteract Tumor Glycolysis

Anticancer Agents That Counteract Tumor Glycolysis

Synthesis and Structure Elucidation of Benzoylated Deoxyfluoropyranosides

6‐Deoxyhexoses from l‐Rhamnose in the Search for Inducers of the Rhamnose Operon: Synergy of Chemistry and Biotechnology

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