Use of Catalytic Fluoride under Neutral Conditions for Cleaving Silicon–Oxygen Bonds

DiLauro, Anthony M.; Seo, Wanji; Phillips, Scott T.

doi:10.1021/jo200848j

Cited by 45 publications

(71 citation statements)

References 31 publications

(57 reference statements)

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“…Treatment with dibenzyl N , N ‐diisopropylphosphoramidite and subsequent oxidation with m CPBA gave the fully protected phosphate 15 in excellent yield (99 %) . Removal of the TBS group by sub‐stoichiometric quantities of TBAF (41 % yield), followed by debenzylation under similar conditions as described above, gave 2 in 68 % yield. The configurations of 14 and 2 were analyzed by NMR, which revealed coupling constants 3 J H3–H4 = 3 J H3–H2 =6.1 Hz for 14 and 2 .…”

Section: Resultsmentioning

confidence: 86%

Fluoro‐Carba‐Sugars are Glycomimetic Activators of the glmS Ribozyme

Matzner

Schüller

Seitz

et al. 2017

Chemistry A European J

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The glmS ribozyme is a bacterial gene-regulating riboswitch that controls cell wall synthesis, depending on glucosamine-6-phosphate as a cofactor. Due to the presence of this ribozyme in several human pathogen bacteria (e.g., MRSA, VRSA), the glmS ribozyme represents an attractive target for the development of artificial cofactors. The substitution of the ring oxygen in carbohydrates by functionalized methylene groups leads to a new generation of glycomimetics that exploits distinct interaction possibilities with their target structure in biological systems. Herein, we describe the synthesis of mono-fluoro-modified carba variants of α-d-glucosamine and β-l-idosamine. (5aR)-Fluoro-carba-α-d-glucosamine-6-phosphate is a synthetic mimic of the natural ligand of the glmS ribozyme and is capable of effectively addressing its unique self-cleavage mechanism. However, in contrast to what was expected, the activity is significantly decreased compared to its non-fluorinated analog. By combining self-cleavage assays with the Bacillus subtilis and Staphylococcus aureus glmS ribozyme and molecular docking studies, we provide a structure-activity relationship for fluorinated carba-sugars.

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Section: Resultsmentioning

confidence: 86%

Fluoro‐Carba‐Sugars are Glycomimetic Activators of the glmS Ribozyme

Matzner

Schüller

Seitz

et al. 2017

Chemistry A European J

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“…We surmise that N 1 -POB cleavage occurred via an enolate-ring closure that released dIno and presumably a cyclopropyl byproduct. 48 When recently developed conditions using catalytic fluoride and neutral pH buffer were applied, 43 selective TBS cleavage was observed. In agreement with the enolate-ring closure hypothesis, unbuffered TBAF could be used to deprotect compound 35 with no cleavage of the PHB group.…”

Section: Discussionmentioning

confidence: 99%

Analysis and Identification of 2′-Deoxyadenosine-Derived Adducts in Lung and Liver DNA of F-344 Rats Treated with the Tobacco-Specific Carcinogen 4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanone and Enantiomers of its Metabolite 4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanol

Carlson

Upadhyaya

Villalta

et al. 2018

Chem. Res. Toxicol.

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4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) and its metabolite 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) are carcinogenic in animal models and are believed to play an important role in human lung carcinogenesis in cigarette smokers. Cytochrome P450-mediated metabolism of these tobacco-specific nitrosamines produces reactive species that alkylate DNA in the form of pyridyloxobutyl (POB)- or pyridylhydroxybutyl (PHB)-DNA adducts. Understanding the formation mechanism and overall levels of these adducts can potentially enhance cancer prevention methods through the identification of particularly susceptible smokers. Previous studies have identified and measured a panel of POB- and PHB-DNA base adducts of dGuo, dCyd, and Thd; however, dAdo adducts have yet to be determined. In this study, we complete this DNA adduct panel by identifying and quantifying levels of NNK- and NNAL-derived dAdo adducts in vitro and in vivo. To accomplish this, we synthesized standards for expected dAdo-derived DNA adducts and used isotope-dilution LC-ESI+-MS/MS to identify POB adducts formed in vitro from the reaction of 4-(acetoxymethylnitrosamino)-1-(3-pyridyl)-1-butanone (NNKOAc) with calf thymus DNA. Adduct levels were then quantified in lung and liver DNA of rats chronically treated with NNK or NNAL for 50 weeks using similar LC-MS detection methods. The in vitro studies identified N6-POB-dAdo and N1-POB-dIno as products of the reaction of NNKOAc with DNA, which supports our proposed mechanism of formation. Though both N6-dAdo and N1-dIno adducts were found in vitro, only N6-dAdo adducts were found in vivo, implying possible intervention by DNA repair mechanisms. Analogous to previous studies, levels of N6-POB-dAdo and N6-PHB-dAdo varied both with tissue and treatment type. Despite the adduct levels being relatively modest compared to most other POB- and PHB-DNA adducts, they may play a biological role and could be used in future studies as NNK- and NNAL-specific DNA damage biomarkers.

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“…Finally, deprotection of the TMS group using tetrabutylammonium fluoride (TBAF) resulting in the free alcohol intermediate product (g) [Fig. (g)] (DiLauro et al ., ) followed by C21 acetate removal with K 2 CO 3 afforded the title compound 1α‐hydroxycorticosterone [Fig. (h)] in a quantitative yield over two steps (Corey et al ., ).…”

Section: Methodsmentioning

confidence: 99%

Biosynthesis of 1α‐hydroxycorticosterone in the winter skate Leucoraja ocellata: evidence to suggest a novel steroidogenic route

Wiens

Brassinga

et al. 2017

Journal of Fish Biology

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The present study explores the ability of intracellular bacteria within the renal-inter-renal tissue of the winter skate Leucoraja ocellata to metabolize steroids and contribute to the synthesis of the novel elasmobranch corticosteroid, 1α-hydroxycorticosterone (1α-OH-B). Despite the rarity of C1 hydroxylation noted in the original identification of 1α-OH-B, literature provides evidence for steroid C1 hydroxylation by micro-organisms. Eight ureolytic bacterial isolates were identified in the renal-inter-renal tissue of L. ocellata, the latter being the site of 1α-OH-B synthesis. From incubations of bacterial isolates with known amounts of potential 1α-OH-B precursors, one isolate UM008 of the genus Rhodococcus was seen to metabolize corticosteroids and produce novel products via HPLC analysis. Cations Zn and Fe altered metabolism of certain steroid precursors, suggesting inhibition of Rhodococcus steroid catabolism. Genome sequencing of UM008 identified strong sequence and structural homology to that of Rhodococcus erythropolis PR4. A complete enzymatic pathway for steroid-ring oxidation as documented within other Actinobacteria was identified within the UM008 genome. This study highlights the potential role of Rhodococcus bacteria in steroid metabolism and proposes a novel alternative pathway for 1α-OH-B synthesis, suggesting a unique form of mutualism between intracellular bacteria and their elasmobranch host.

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Use of Catalytic Fluoride under Neutral Conditions for Cleaving Silicon–Oxygen Bonds

Cited by 45 publications

References 31 publications

Fluoro‐Carba‐Sugars are Glycomimetic Activators of the glmS Ribozyme

Fluoro‐Carba‐Sugars are Glycomimetic Activators of the glmS Ribozyme

Analysis and Identification of 2′-Deoxyadenosine-Derived Adducts in Lung and Liver DNA of F-344 Rats Treated with the Tobacco-Specific Carcinogen 4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanone and Enantiomers of its Metabolite 4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanol

Biosynthesis of 1α‐hydroxycorticosterone in the winter skate Leucoraja ocellata: evidence to suggest a novel steroidogenic route

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