Facile Cleavage of Disulfides and Preparation of Unsymmetrical Sulfides, Thioglycosides, and Michael Adducts Using Triphenylphosphine

C. Mukherjee; A.K. Misra

doi:10.1021/jo060328w

Histone Carbonylation Is a Redox-Regulated Epigenomic Mark That Accumulates with Obesity and Aging

Antioxidants ◽

10.3390/antiox9121210 ◽

2020 ◽

Vol 9 (12) ◽

pp. 1210

Author(s):

Amy K. Hauck ◽

Tong Zhou ◽

Ambuj Upadhyay ◽

Yuxiang Sun ◽

Michael B. O’Connor ◽

...

Keyword(s):

Oxidative Stress ◽

Metabolic Disease ◽

Adipose Tissue ◽

Fat Depots ◽

Michael Adducts ◽

Lipid Aldehydes ◽

Visceral Adipose ◽

Fat Feeding

Oxidative stress is a hallmark of metabolic disease, though the mechanisms that define this link are not fully understood. Irreversible modification of proteins by reactive lipid aldehydes (protein carbonylation) is a major consequence of oxidative stress in adipose tissue and the substrates and specificity of this modification are largely unexplored. Here we show that histones are avidly modified by 4-hydroxynonenal (4-HNE) in vitro and in vivo. Carbonylation of histones by 4-HNE increased with age in male flies and visceral fat depots of mice and was potentiated in genetic (ob/ob) and high-fat feeding models of obesity. Proteomic evaluation of in vitro 4-HNE- modified histones led to the identification of both Michael and Schiff base adducts. In contrast, mapping of sites in vivo from obese mice exclusively revealed Michael adducts. In total, we identified 11 sites of 4-hydroxy hexenal (4-HHE) and 10 sites of 4-HNE histone modification in visceral adipose tissue. In summary, these results characterize adipose histone carbonylation as a redox-linked epigenomic mark associated with metabolic disease and aging.

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High-quality oligo-RNA synthesis using the new 2′-O-TEM protecting group by selectively quenching the addition of p-tolyl vinyl sulphone to exocyclic amino functions

Canadian Journal of Chemistry ◽

10.1139/v07-025 ◽

2007 ◽

Vol 85 (4) ◽

pp. 293-301 ◽

Cited By ~ 11

Author(s):

Chuanzheng Zhou ◽

Wimal Pathmasiri ◽

Dmytro Honcharenko ◽

Subhrangsu Chatterjee ◽

Jharna Barman ◽

...

Keyword(s):

Michael Addition ◽

Chemical Biology ◽

Rna Synthesis ◽

Spectroscopic Analysis ◽

Multiple Bond ◽

Protecting Group ◽

High Quality ◽

Heteronuclear Multiple Bond Correlation ◽

Michael Adducts

During the F–-promoted deprotection of the oligo–RNA, synthesized using our 2′-O-(4-tolylsulfonyl)ethoxymethyl (2′-O-TEM) group [Org. Biomol. Chem. 5, 333 (2007)], p-tolyl vinyl sulphone (TVS) is formed as a by-product. The TVS formed has been shown to react with the exocyclic amino functions of adenosine (A), guanosine (G), and cytidine (C) of the fully deprotected oligo–RNA to give undesirable adducts, which are then purified by HPLC and unambiguously characterized by 1H, 13C Heteronuclear Multiple Bond Correlation (HMBC) NMR and mass spectroscopic analysis. The relative nucleophilic reactivities of the nucleobases toward TVS have been found to be the following: N6–A > N4–C > N2–G > > N3–U. This reactivity of TVS toward RNA nucleobases to give various Michael adducts could, however, be suppressed by using various amines as scavengers. Among all these amines, morpholine and piperidine are the most efficient scavenger for TVS, which gave highly pure oligo–RNA even in the crude form and can be used directly in RNA chemical biology studies.Key words: RNA synthesis, RNA alkylation, p-tolyl vinyl sulphone, Michael addition.

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Synthesis and reactivity of Michael adducts of cyclic β-ketoesters enolates with electrophilic acetylenes

Tetrahedron Letters ◽

10.1016/s0040-4039(98)01500-7 ◽

1998 ◽

Vol 39 (38) ◽

pp. 6873-6876 ◽

Cited By ~ 7

Author(s):

Michel Miesch ◽

Gaëtan Mislin ◽

Michel Franck-Neumann

Keyword(s):

Michael Adducts

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Michael adducts of a half-blocked enedione as sources of 3-substituted 2,5-diketones and 2,5-dialkylfurans

The Journal of Organic Chemistry ◽

10.1021/jo00362a032 ◽

1986 ◽

Vol 51 (12) ◽

pp. 2351-2361 ◽

Cited By ~ 22

Author(s):

Donald Mackay ◽

Edward G. Neeland ◽

Nicholas J. Taylor

Keyword(s):

Michael Adducts

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ChemInform Abstract: Dihalogenotriphenylphosphoranes in Heterocyclic Synthesis. Part 10. Reactions of Uracils. Part 10. Novel Michael Adducts of Uracils and New Synthesis of Imidazo(5,1-f)(1,2,4)triazines.

ChemInform ◽

10.1002/chin.198707222 ◽

1987 ◽

Vol 18 (7) ◽

Author(s):

H. WAMHOFF ◽

W. SCHUPP

Keyword(s):

Heterocyclic Synthesis ◽

Michael Adducts ◽

New Synthesis

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An Unequivocal Synthesis of 4-Amino-1,5,6,8-tetrahydropyrido[2,3-d]pyrimidine-2,7-diones and 2-Amino-3,5,6,8-tetrahydropyrido[2,3-d]pyrimidine-4,7-diones

Collection of Czechoslovak Chemical Communications ◽

10.1135/cccc19960901 ◽

1996 ◽

Vol 61 (6) ◽

pp. 901-909 ◽

Cited By ~ 12

Author(s):

José I. Borrell ◽

Jordi Teixidó ◽

Blanca Martínez-Teipel ◽

Blanca Serra ◽

Josep Lluís Matallana ◽

...

Keyword(s):

Acid Hydrolysis ◽

Unsaturated Ester ◽

Michael Adducts ◽

Hydrolysis Of

An unequivocal set of procedures for the synthesis of 4-amino-1,5,6,8-tetrahydropyrido[2,3-d]pyrimidine-2,7-diones (7) and 2-amino-3,5,6,8-tetrahydropyrido[2,3-d]pyrimidine-4,7-diones (8), in a maximum of four steps from an α,β-unsaturated ester 1, is reported. Thus, the acid hydrolysis of the 2,4-diaminopyrido[2,3-d]pyrimidines 3 yields the 4-amino-2-oxopyrido[2,3-d]pyrimidines 7 while the cyclization of the Michael adducts 9 (formed by reaction of 1 and methyl cyanoacetate) with guanidine affords the corresponding 2-amino-4-oxopyrido[2,3-d]pyrimidines 8. Both isomers were also obtained by hydrolysis of the 4-amino-2-bromo- and 2-amino-4-bromo-5,6-dihydropyrido[2,3-d]pyrimidin-7(8H)-ones 5 and 6, respectively.

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