Ethyl Diazoacetate

Searle, Norman E.

doi:10.1002/0471264180.os036.11

Cited by 7 publications

(11 citation statements)

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“…The labeled compound was prepared by slight modification of the reported method. 16 In a 50 mL three-necked round-bottomed flask, equipped with an argon inlet, septum cap, and thermometer, were placed 1.0 g (7.2 mmol) of ethylglycine hydrochloride, 2 mL of H 2 O, and 4 mL of CH 2 Cl 2 , and the mixture was cooled to ca. −5 °C.…”

Section: ■ Experimental Sectionmentioning

confidence: 99%

Pentamethylcyclopentadienyl Half-Sandwich Diazoalkane Complexes of Ruthenium: Preparation and Reactivity

et al. 2016

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The diazoalkane complexes [Ru(η(5)-C5Me5)(N2CAr1Ar2){P(OR)3}L]BPh4 (1-4) [R = Me, L = P(OMe)3 (1); R = Et, L = P(OEt)3 (2); R = Me, L = PPh3 (3); R = Et, L = PPh3 (4); Ar1 = Ar2 = Ph (a); Ar1 = Ph, Ar2 = p-tolyl (b); Ar1Ar2 = C12H8 (c); Ar1 = Ph, Ar2 = PhC(O) (d)] and [Ru(η(5)-C5Me5){N2C(C12H8)}{PPh(OEt)2}(PPh3)]BPh4 (5c) were prepared by allowing chloro-compounds RuCl(η(5)-C5Me5)[P(OR)3]L to react with the diazoalkane Ar1Ar2CN2 in the presence of NaBPh4. Treatment of complexes 1-4 with H2O afforded 1,2-diazene derivatives [Ru(η(5)-C5Me5)(η(2)-NH═NH){P(OR)3}L]BPh4 (6-9) and ketone Ar1Ar2CO. A reaction path involving nucleophilic attack by H2O on the coordinated diazoalkane is proposed and supported by density functional theory calculations. The complexes were characterized spectroscopically (IR and (1)H, (31)P, (13)C, (15)N NMR) and by X-ray crystal structure determination of [Ru(η(5)-C5Me5)(N2CC12H8){P(OEt)3}2]BPh4 (2c) and [Ru(η(5)-C5Me5)(η(2)-NH═NH){P(OEt)3}2]BPh4 (7).

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Section: ■ Experimental Sectionmentioning

confidence: 99%

Pentamethylcyclopentadienyl Half-Sandwich Diazoalkane Complexes of Ruthenium: Preparation and Reactivity

et al. 2016

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“…The conversion to [ 13 C 2 ]ethyl diazoaceate was performed by a known procedure [8] , and converted to 5 in the same manner as for 4. The major difference in the NMR, between the labelled and unlabelled compounds, was either the lack of a peak or the very large coupling constants observed between protons and the C-13 atoms in the labelled compounds which enabled unambiguous assignment of the NMR spectra.…”

Section: Resultsmentioning

confidence: 99%

Synthesis of deuterium and C‐13‐labelled ethyl glycolate and their subsequent use in the synthesis of labelled analogues of the DNA adduct O⁶‐carboxymethyl‐2′‐deoxyguanosine

Moore

Shuker

2011

Labelled Comp Radiopharmac

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The adduct O6‐carboxymethyl‐2′‐deoxyguanosine (O6CMdG) is of importance as it has been previously linked to high red meat diet in humans, and as yet, a liquid chromatography‐mass spectrometry (LC‐MS) method has not been developed due to lack of appropriate standards. The synthesis of the deuterated and C‐13 analogues required the use of [2H2]‐ and [13C2]ethyl glycolate to label the carboxymethyl moiety of O6CMdG. [2H2]Ethyl glycolate was synthesised via acid hydrolysis of ethyl diazoacetate using deuterated solvents (59% yield), whilst [13C2]ethyl glycolate was synthesised from [13C2]glycine in a three‐step procedure (35% yield). The labelled ethyl glycolates were then used to synthesise [2H2]‐ and [13C2]O6CMdG for future use as internal standards in the LC‐MS analysis of biological samples. Copyright © 2011 John Wiley & Sons, Ltd.

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“…97 Much effort is focused around creating safer synthetic routes for these explosive compounds 98,99 or making them more environmentally friendly by removing the necessity for heavy metals. 97b To this end, a modification of the well-documented procedure initially published by Searle 100 in 1955 was utilised 101,97 where ethyl glycinate hydrochloride 47 was reacted with sodium nitrite at -9 °C. Care was taken to maintain the reaction at -9 °C during the addition of concentrated sulfuric acid as increases in temperature have been reported…”

Section: Synthesis Of (((2r3s4r)-34-bis(benzyloxy)-34-dihydro-2hpyran-2-yl)methoxy)(tert-butyl)diphenylsilane (45)mentioning

confidence: 99%

“…Due to the explosive nature of the diazo compound 49, the final product was not concentrated and a yield of 70% was assumed as per the literature (scheme 2.11). 100 Furthermore, due to the specific warning about the especially explosive nature of methyl diazoacetates (69), 100 it was decided to discontinue its synthesis.…”

Section: CLmentioning

confidence: 99%

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Identifying the Mechanism of Action of Bioactive 1,2-Cyclopropyl Carbohydrates

Lassueur¹

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<p>Cyclopropanes and carbohydrates have long been used in the field of drug development. Previous work has shown that 1,2-cyclopropyl carbohydrates display bioactivity in both HeLa cancer cell lines¹ and in yeast² with a tentatively proposed mechanism of inhibition occurring through an enzymatic cyclopropane ring opening reaction and subsequent formation of a covalent bond with a target enzyme.² A small library of 1,2-cyclopropyl carbohydrate derivatives were synthesised based on known pharmacophores to examine further the potential mechanism of inhibition of such compounds and confirm the occurrence of enzyme-catalysed cyclopropane ring-opening reactions. Initial synthetic efforts were focused on the synthesis of the 1,2-dichlorocyclopropyl carbohydrate 23, which, through the optimisation of an essential C-6 detritylation reaction, was achieved in moderate yields of 32% over 7 steps. Following this, the ethoxycarbonyl substituted 1,2-cyclopropyl carbohydrate 54 was synthesised over 7 steps in a 22% yield through a rhodium acetate-catalysed addition of ethyl diazoacetate (49) to the glucal substrate 40. It was envisioned that if enzymatic cyclopropane ring-opening was occurring to form a C-7 carbanion, this would in turn be stabilised through the potential enolate formation of 54. Use of N,N-ditosylhydrazine in the synthesis of propargyl diazoacetate (58) followed by a rhodium acetate-catalysed cyclopropanation of 58 with substrate 40 resulted in the successful synthesis of 61 over 7 steps in a total yield of 9%. The incorporation of the propargyl substituent in 61 was introduced as a molecular probe in an attempt to isolate the target protein through an affinity purification procedure. The bioactivity of the propargyl derivative 61 was consistent with the synthesised compounds 23 and 54. It was proposed that these compounds undergo an enzymatic cyclopropane ring opening reaction accompanied with a clear diastereoselective preference for the α-stereoisomer of the cyclopropane ring, consistent with a target-based activation of the compounds. Chemical genetic analysis of the resulting bioactive compounds was undertaken using a deletion mutant array of Saccharomyces cerevisiae to elucidate a potential mechanism of action. Analysis of the results showed that, of the 4800 homozygous deletion strains tested in the high-throughput screens, a total of 122 strains were found following validation to sensitise and 68 to give resistance against 23 and 54. These sensitive and resistant mutants were subjected to a validation assay. Following validation, genes whose deletion led to sensitivity or resistance were then subjected to gene ontology term enrichment analysis which showed enrichment in the cytosolic ribosome, SNARE complex and SNAP receptor activity for resistant strains and enrichment in endoplasmic reticulum and endomembrane systems was found for the sensitive strain. Genes whose deletion sensitised to both compounds showed strong enrichment in cellular protein localisation, intra-golgi vesicale-mediated transport and the endomembrane system. Target identification and isolation were attempted through an affinity purification procedure using compound 61 and an azide-modified agarose resin. However, this was without success, either through inaccessibility of the alkyne of the target probe or because the target resides in the membrane-associated fraction which was discarded prior to treatment with the probe. This study suggests that the 1,2-cyclopropyl carbohydrates synthesised function through a cyclopropane ring-opening reaction, assisted by an enzymatic nucleophile. Chemical genetic analysis showed that the target of these compounds is involved in protein transport and protein localisation most likely relating to the vesicle tethering. Although many aspects of this work still need further investigation, either through the synthesis of new 1,2-cyclopropyl carbohydrates to increase bioactivity and better understand the enzymatic target, or through further biological procedures to better understand the mechanism of action, the use of 1,2-cyclopropyl carbohydrates as a potential pharmaceuticals or probes of protein trafficking shows much promise.</p>

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Ethyl Diazoacetate

Abstract: Ethyl diazoacetate product: ethyl diazoacetate

Cited by 7 publications

References 0 publications

Pentamethylcyclopentadienyl Half-Sandwich Diazoalkane Complexes of Ruthenium: Preparation and Reactivity

Pentamethylcyclopentadienyl Half-Sandwich Diazoalkane Complexes of Ruthenium: Preparation and Reactivity

Synthesis of deuterium and C‐13‐labelled ethyl glycolate and their subsequent use in the synthesis of labelled analogues of the DNA adduct O⁶‐carboxymethyl‐2′‐deoxyguanosine

Identifying the Mechanism of Action of Bioactive 1,2-Cyclopropyl Carbohydrates

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Ethyl Diazoacetate

Abstract: Ethyl diazoacetate product: ethyl diazoacetate

Cited by 7 publications

References 0 publications

Pentamethylcyclopentadienyl Half-Sandwich Diazoalkane Complexes of Ruthenium: Preparation and Reactivity

Pentamethylcyclopentadienyl Half-Sandwich Diazoalkane Complexes of Ruthenium: Preparation and Reactivity

Synthesis of deuterium and C‐13‐labelled ethyl glycolate and their subsequent use in the synthesis of labelled analogues of the DNA adduct O6‐carboxymethyl‐2′‐deoxyguanosine

Identifying the Mechanism of Action of Bioactive 1,2-Cyclopropyl Carbohydrates

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Synthesis of deuterium and C‐13‐labelled ethyl glycolate and their subsequent use in the synthesis of labelled analogues of the DNA adduct O⁶‐carboxymethyl‐2′‐deoxyguanosine