scholarly journals Exploring hydrogen peroxide responsive thiazolidinone-based prodrugs

2015 ◽  
Vol 51 (33) ◽  
pp. 7116-7119 ◽  
Author(s):  
Christian Perez ◽  
Jean-Philippe Monserrat ◽  
Yao Chen ◽  
Seth M. Cohen
Keyword(s):  
Hydrogen Peroxide ◽  
Carboxylic Acid ◽  
Protecting Group

A thiazolidinone moiety was found to serve as a protecting group for releasing carboxylic acid-containing therapeutics in the presence of hydrogen peroxide.

The Theodorakis Synthesis of (–)-Jiadifenolide

2015 ◽  
Author(s):  
Douglass F. Taber
Keyword(s):  
Hydrogen Peroxide ◽  
Carboxylic Acid ◽  
Aldol Condensation ◽  
University Of California ◽  
Oxidative Rearrangement ◽  
Promote Neurite Outgrowth ◽  
Starting Point ◽  
Jones Reagent ◽  
Acid Catalyzed ◽  
The University

There has recently been a great deal of interest in the synthesis of natural products that promote neurite outgrowth. Emmanuel A. Theodorakis of the University of California, San Diego described (Angew. Chem. Int. Ed. 2011, 50, 3672) the preparation of one of the most potent (10 nM) of these, (–)-jiadifenolide 3. Fittingly, a key transformation en route to this highly oxygenated seco-prezizaane was the oxidative rearrangement of 1 to 2. The starting point for the synthesis was the commercially available diketone 4. Allylation followed by addition to 5 gave the prochiral triketone 6. Enantioselective aldol condensation following the Tu/Zhang protocol then delivered the bicyclic enone 7. Alkylation to give 8 proceeded with high diastereoselectivity, perhaps controlled by the steric bulk of the silyloxy group. Exposure of the protected ketone to the McMurry reagent PhNTf2 gave the enol triflate 9, which smoothly carbonylated to the lactone 10. Epoxidation with alkaline hydrogen peroxide followed by oxidation gave the carboxylic acid, which spontaneously opened the epoxide, leading to the bis lactone 1. With 1 in hand, the stage was set for the key oxidative rearrangement to 2. It was envisioned that epoxidation would generate the cis-fused 11, which on oxidation would undergo acid-catalyzed elimination to give 12. The newly freed OH would then be in position to engage the lactone carbonyl, leading to 2. In the event, oxidation of the epoxide with the Dess-Martin reagent required sonication for 2 h. The rearranged lactone, even though it was susceptible to further oxidation, was secured in 38% overall yield from 1. After hydrogenation and protection, preparation of the enol triflate 13 from the congested cyclopentanone necessitated the use of the more reactive Comins reagent. Hydrogenation of the trisubstituted alkene from coupling with Me3Al then required 90 atmospheres of H2 overpressure. Hydroxylation of the lactone 14 with the Davis oxaziridine followed by further oxidation to the ketone with the Jones reagent and deprotection then completed the synthesis of (–)-jiadifenolide 3.

Identification of a Copper(I) Intermediate in the Conversion of 1-Aminocyclopropane Carboxylic Acid (ACC) into Ethylene by Cu(II)−ACC Complexes and Hydrogen Peroxide

2008 ◽  
Vol 47 (11) ◽  
pp. 4627-4638 ◽  
Author(s):  
Wadih Ghattas ◽  
Michel Giorgi ◽  
Yasmina Mekmouche ◽  
Tsunehiro Tanaka ◽  
Antal Rockenbauer ◽  
...  
Keyword(s):  
Hydrogen Peroxide ◽  
Carboxylic Acid

Flavonoid intermediates for the synthesis of mopanol trimethyl ether[trans-trans-7,7',8'-Trimethoxyisochromano(4',3':2,3)chroman-4-ol]

1976 ◽  
Vol 29 (1) ◽  
pp. 191 ◽  
Author(s):  
JW Clark-Lewis ◽  
DP Cox
Keyword(s):  
Carboxylic Acid ◽  
Potassium Carbonate ◽  
Dimethyl Sulphate ◽  
Metal Hydrides ◽  
Cyclic Ether ◽  
Protecting Group ◽  
Model Compounds ◽  
Initial Product ◽  
Dibenzyl Ether ◽  
Trimethyl Ether

Preparation of a number of intermediates for the synthesis of (�)-mopanol trimethyl ether is described, together with exploratory reactions with model compounds, and especially with 7-methoxyflavanone-2'-carboxylic acid. 7-Methoxyflavan-4-ol, the initial product from reduction of 7-methoxyflavanone-2'-carboxylic acid with complex metal hydrides, was found to undergo facile dehydration to a novel intramolecular dibenzyl ether [the cyclic ether (19)*]. It was noted that the methoxymethyl group, which may be used as a protecting group for phenols, did not survive the conditions of methylation with dimethyl sulphate and potassium carbonate in acetone.

Thietanyl Protection in the Synthesis of 8-Substituted 1-Benzyl-3-methyl-3,7-dihydro- 1H-purine-2,6-diones

2020 ◽  
Vol 17 (7) ◽  
pp. 535-539
Author(s):  
Ferkat Khaliullin ◽  
Yuliya Shabalina
Keyword(s):  
Hydrogen Peroxide ◽  
Benzyl Chloride ◽  
Bromine Atom ◽  
Protecting Groups ◽  
15N Nmr ◽  
Protecting Group ◽  
Mild Conditions ◽  
Protective Groups ◽  
The Stability ◽  
Substituted 1

Aim and Objective: 1-Аlkyl-3,7-dihydro-1H-purine-2,6-diones containing no substituents in the N7 position can be synthesized only using protecting groups, for example, benzyl protection. However, in the case of synthesis of 1-benzyl-3,7-dihydro-1H-purine-2,6-diones, the use of benzyl protection may lead to simultaneous debenzylation of both N1 and N7 positions. Therefore, it is necessary to use other protective groups for the synthesis of 1-benzyl-3,7-dihydro-1H-purine-2,6-diones. Materials and Methods: 8-Bromo- and 8-amino-substituted 1-benzyl-3-methyl-3,7-dihydro-1H-purine-2,6-diones unsubstituted in the N7 position were synthesized with the use of thietanyl protecting group. The thietane ring was introduced via the reaction of 8-bromo-3-methyl-3,7-dihydro-1H-purine-2,6-dione with 2-chloromethylthiirane, giving rise to 8-bromo-3-methyl-7-(thietan-3-yl)-3,7-dihydro-1H-purine-2,6-dione. The subsequent alkylation with benzyl chloride yielded 1-benzyl-8-bromo-3-methyl-7-(thietan-3-yl)-3,7-dihydro-1H-purine-2,6-dione, which was oxidized with hydrogen peroxide to be converted to 1-benzyl-8-bromo-3-methyl-7-(1,1-dioxothietan- 3-yl)-3,7-dihydro-1H-purine-2,6-dione. This product reacted with amines to give 8-amino-substituted 1-benzyl-3- methyl-7-(1,1-dioxothietan-3-yl)-3,7-dihydro-1H-purine-2,6-diones. The reaction of 8-substituted 1-benzyl-3- methyl-7-(1,1-dioxothietan-3-yl)-3,7-dihydro-1H-purine-2,6-diones with sodium isopropoxide resulted in the removal of the thietanyl protection and afforded target 8-substituted 1-benzyl-3-methyl-3,7-dihydro-1H-purine-2,6- diones. The structures of the targets compounds have been deduced upon their elemental analysis and spectral data (IR, 1H NMR, 13C NMR and 15N NMR). Results and Discussion: A new 8-substituted 1-benzyl-3-methyl-3,7-dihydro-1H-purine-2,6-diones unsubstituted in the N7 position were synthesized using thietanyl protecting group. Conclusion: The present study described a new route to synthesize some new 1,8-disubstituted 3-methyl-3,7- dihydro-1H-purine-2,6-diones unsubstituted in the N7 position starting from available 8-bromo-3-methyl-3,7- dihydro-1H-purine-2,6-dione with use of thietanyl protecting group. The advantages of this protocol are the possibility of the synthesis of 1-benzyl-substituted 3,7-dihydro-1H-purine-2,6-diones, the stability of the thietanyl protecting group upon nucleophilic substitution by amines of the bromine atom in the position 8, as well as mild conditions, and simple execution of experiments.

Semipermanent C-Terminal Carboxylic Acid Protecting Group: Application to Solubilizing Peptides and Fragment Condensation

2014 ◽  
Vol 17 (2) ◽  
pp. 294-297 ◽  
Author(s):  
Marta Paradís-Bas ◽  
Judit Tulla-Puche ◽  
Fernando Albericio
Keyword(s):  
Carboxylic Acid ◽  
Protecting Group ◽  
Fragment Condensation

Fast kinetic studies of dioxygen-derived species and their metal complexes

1985 ◽  
Vol 311 (1152) ◽  
pp. 473-482 ◽  
Keyword(s):  
Hydrogen Peroxide ◽  
Carboxylic Acid ◽  
Transition Metal Complex ◽  
Kinetic Studies ◽  
Ph Effects ◽  
Ferric Ion ◽  
Rate Data ◽  
Biological Interest ◽  
Fast Kinetic

The role of metals in the reactivity of HO 2 /O - 2 with compounds of biological interest is discussed. A scheme that illustrates the various reactions that a transition metal complex can undergo when reacting with HO 2 /O - 2 is presented in terms of ligand and pH effects. The decomposition of hydrogen peroxide catalysed by ferrous ion is reviewed in terms of new rate data for the reactions of ferric ion with perhydroxyl (HO 2 ) and superoxide (O - 2 ) radicals. The new results support a mechanism proposed by Barb and his coworkers (W. G. Barb, J. H. Baxendale, P. George & K. R. Hargrave, Trans. Faraday Soc. 47, 462-500 (1951)) and negates the occurrence of the Haber—Weiss reaction in this system. In the presence of Mn II complexes, O - 2 reacts to form MnO + 2 transients and Mn III complexes. Their reactivities with ascorbate, Trolox (6-hydroxy-2,5,7,8- tetramethylchroman-2-carboxylic acid) and NADH-NADPH is discussed.

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