CARCINOGENICITY OF LACTONES: I. THE REACTION OF 4-METHYLBUTENO- AND 4-METHYLBUTANO-γ-LACTONES WITH PRIMARY AMINES

1966 ◽  
Vol 44 (9) ◽  
pp. 1059-1068 ◽  
Author(s):  
J. Bryan Jones ◽  
John M. Young
Keyword(s):  
Magnetic Resonance ◽  
Michael Addition ◽  
Ring Opening ◽  
Proton Magnetic Resonance ◽  
Mechanisms Of Action ◽  
Reaction Pathways ◽  
Nucleophilic Attack ◽  
Primary Amines ◽  
Acid Lactone ◽  
The Michael Addition

As the first stage in the investigations of the mechanisms of action of carcinogenic lactones, the reactions of 4-hydroxypent-2-enoic acid lactone (II, R = CH3), which is a carcinogen, and of the non-carcinogenic 4-hydroxypent-3-enoic (III, R = CH3) and 4-hydroxypentanoic (IV, R = CH3) acid lactones with methylamine and benzylamine have been studied. As expected, the carcinogenic lactone reacts to give the Michael addition products, whereas both inactive lactones undergo ring opening by nucleophilic attack at the carbonyl group. From the relative rates of reaction of the amines with the lactones it is concluded that the induction of tumors by II (R = CH3) does not involve alkylation of biological primary alkylamino groups. The proton magnetic resonance spectra of the products enable the different reaction pathways to be distinguished readily, and may provide the basis for rapid physicochemical screening of alkylation agents that are potential carcinogens.

Carcinogenicity of lactones. V. The reactions of 4-hydroxypent-2-enoic acid lactone with α-toluenethiol, benzylamine, methylamine, imidazole, and guanidine

1970 ◽  
Vol 48 (10) ◽  
pp. 1574-1578 ◽  
Author(s):  
J. Bryan Jones ◽  
Jill N. Barker
Keyword(s):  
Michael Addition ◽  
Ring Opening ◽  
Lactone Ring ◽  
Addition Product ◽  
Enoic Acid ◽  
Michael Additions ◽  
Ring Opening Reactions ◽  
Acid Lactone ◽  
Ph Range ◽  
The Michael Addition

The Michael additions of α-toluenethiol, methylamine, and benzylamine to 4-hydroxypent-2-enoic acid lactone have been confirmed to be facile. The analogous additions of imidazole and glycine amide are much less readily accomplished and no stable Michael addition product could be detected with guanidine as the base. In the pH range 6–9, subsequent lactone ring opening reactions of the Michael addition products were observed only when methylamine (pKa 9.3) and benzylamine (pKa 10.6) were used as nucleophiles.

Synthesis of phenethanolamine derivatives with potential β-adrenergic antagonistic activity

1975 ◽  
Vol 28 (5) ◽  
pp. 1023 ◽  
Author(s):  
SJ Pasaribu ◽  
LR Williams
Keyword(s):  
Magnetic Resonance ◽  
Ring Opening ◽  
Proton Magnetic Resonance ◽  
Mass Spectra ◽  
Antagonistic Activity ◽  
Spectral Studies ◽  
Aryl Ring ◽  
Mass Spectral

The mass spectra of bromonitroacetophenones, intermediates in the synthesis of phenethanolamine derivatives containing a nitro and bromo group in the aryl ring, have been studied. The acetophenones were converted into the corresponding α,β-epoxystyrenes, which were then treated with various amines, and proton magnetic resonance and mass spectral studies were used to confirm the direction of ring opening and purity of the products.

Curve crossing analysis of LFER data in Michael addition reactions

1992 ◽  
Vol 70 (4) ◽  
pp. 1022-1027 ◽  
Author(s):  
Zeev Gross ◽  
Shmaryahu Hoz
Keyword(s):  
Chemical Shift ◽  
Transition State ◽  
Michael Addition ◽  
Electronic Configuration ◽  
Nucleophilic Attack ◽  
Addition Reactions ◽  
Rate Correlation ◽  
The Michael Addition ◽  
Curve Crossing

Rate constants for the Michael addition of CN− in water, aqueous sulfolane, and DMSO, and MeO− in MeOH to eight mono- and disubstituted 1,1-diaryl-2,2-dinitroethylenes were measured. The ρ values are in the range 0.7 (CN−/H2O) –1.6 (MeO−/MeOH). For each of the four systems a correlation was found between log k and the 13C chemical shift of the carbon that undergoes the nucleophilic attack. However, the quality of the correlation as well as the slope decreases with decreasing ρ values. Analysis of the electronic configuration of the transition state using the curve crossing model shows that the traditional interpretation of the location of the transition state should be reversed. This analysis provides a rationale for the observed dependence of the chemical shift – rate correlation on the ρ value.

Indium(I) iodide promoted cleavage of dialkyl disulfides — Application of the Michael addition of thiolate anions to conjugated carbonyl compounds and regioselective ring opening of epoxides

2006 ◽  
Vol 84 (5) ◽  
pp. 762-770 ◽  
Author(s):  
Brindaban C Ranu ◽  
Tanmay Mandal
Keyword(s):  
Michael Addition ◽  
Ring Opening ◽  
Unsaturated Ketones ◽  
Ring Opening Of Epoxides ◽  
Dialkyl Disulfides ◽  
Carboxylic Esters ◽  
Thiolate Anions ◽  
Neutral Conditions ◽  
Nucleophilic Ring Opening ◽  
The Michael Addition

Indium(I) iodide promotes cleavage of dialkyl disulfides generating thiolate anions that then undergo facile addition to α,β-unsaturated ketones, aldehydes, carboxylic esters, and nitriles under neutral conditions producing corresponding β-ketosulfides or β-cyanosulfides. This strategy has also been used for the regioselective nucleophilic ring opening of epoxides by thiolate anions in presence of indium(III) chloride producing corresponding β-hydroxyphenyl sulfides. The reactions are in general, very clean, high yielding, and reasonably fast. Thus, simple and convenient procedures for the synthesis of β-ketosulfides or β-cyanosulfides and β-hydroxyalkyl sulfides have been developed using this cleavage reaction.Key words: indium(I) iodide, Michael addition, β-ketosulfide, β-cyanosulfide, epoxide, β-hydroxy sulfide.

scholarly journals Purification of a GlutathioneS-Transferase and a Glutathione Conjugate-Specific Dehydrogenase Involved in Isoprene Metabolism in Rhodococcussp. Strain AD45

1999 ◽  
Vol 181 (7) ◽  
pp. 2094-2101 ◽  
Author(s):  
Johan E. T. van Hylckama Vlieg ◽  
Jaap Kingma ◽  
Wim Kruizinga ◽  
Dick B. Janssen
Keyword(s):  
Nuclear Magnetic Resonance ◽  
Carboxylic Acid ◽  
Magnetic Resonance ◽  
Carbon Atom ◽  
Ring Opening ◽  
Nucleophilic Attack ◽  
Epoxide Ring ◽  
Resonance Spectroscopy ◽  
Secondary Alcohols ◽  
Tertiary Carbon

ABSTRACT A glutathione S-transferase (GST) with activity toward 1,2-epoxy-2-methyl-3-butene (isoprene monoxide) andcis-1,2-dichloroepoxyethane was purified from the isoprene-utilizing bacterium Rhodococcus sp. strain AD45. The homodimeric enzyme (two subunits of 27 kDa each) catalyzed the glutathione (GSH)-dependent ring opening of various epoxides. At 5 mM GSH, the enzyme followed Michaelis-Menten kinetics for isoprene monoxide and cis-1,2-dichloroepoxyethane, withV max values of 66 and 2.4 μmol min−1 mg of protein−1 andKm values of 0.3 and 0.1 mM for isoprene monoxide and cis-1,2-dichloroepoxyethane, respectively. Activities increased linearly with the GSH concentration up to 25 mM.1H nuclear magnetic resonance spectroscopy showed that the product of GSH conjugation to isoprene monoxide was 1-hydroxy-2-glutathionyl-2-methyl-3-butene (HGMB). Thus, nucleophilic attack of GSH occurred on the tertiary carbon atom of the epoxide ring. HGMB was further converted by an NAD+-dependent dehydrogenase, and this enzyme was also purified from isoprene-grown cells. The homodimeric enzyme (two subunits of 25 kDa each) showed a high activity for HGMB, whereas simple primary and secondary alcohols were not oxidized. The enzyme catalyzed the sequential oxidation of the alcohol function to the corresponding aldehyde and carboxylic acid and followed Michaelis-Menten kinetics with respect to NAD+ and HGMB. The results suggest that the initial steps in isoprene metabolism are a monooxygenase-catalyzed conversion to isoprene monoxide, a GST-catalyzed conjugation to HGMB, and a dehydrogenase-catalyzed two-step oxidation to 2-glutathionyl-2-methyl-3-butenoic acid.

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