Synthesis of ammonium analogs of carbocationic intermediates in the conversion of presqualene diphosphate to squalene

Capson, Todd L.; Thompson, Michael D.; Dixit, Vandana; Gaughan, R. G.; Poulter, C. Dale

doi:10.1021/jo00260a019

Cited by 17 publications

(2 citation statements)

References 5 publications

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“…2-HEP and HMP were synthesized as previously reported . The following substrate analogues were synthesized according to literature procedures: 2- 18 OH-HEP, (2 R )- and (2 S )-HPP, 3-hydroxypropylphosphonate, 2-hydroxybutylphosphonate, 3-fluoro-2-hydroxypropylphosphonate, 2-fluoroethylphosphonate, phosphonoacetaldehyde, and 1-hydroxyethylphosphonate . Ethylphosphonate and aminoethylphosphonate were purchased from Sigma-Aldrich.…”

Section: Methodsmentioning

confidence: 99%

Hydroperoxylation by Hydroxyethylphosphonate Dioxygenase

2009

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Hydroxyethylphosphonate dioxygenase (HEPD) catalyzes the O2-dependent cleavage of the carbon−carbon bond of 2-hydroxyethylphosphonate (2-HEP) to afford hydroxymethylphosphonate (HMP) and formate without input of electrons or use of any organic cofactors. Two mechanisms have been proposed to account for this reaction. One involves initial hydroxylation of substrate to an acetal intermediate and its subsequent attack onto an Fe(IV)-oxo species. The second mechanism features initial hydroperoxylation of substrate followed by a Criegee rearrangement. To distinguish between the two mechanisms, substrate analogues were synthesized and presented to the enzyme. Hydroxymethylphosphonate was converted into phosphate and formate, and 1-hydroxyethylphosphonate was converted to acetylphosphate, which is an inhibitor of the enzyme. These results provide strong support for a Criegee rearrangement with a phosphorus-based migrating group and require that the O−O bond of molecular oxygen is not cleaved prior to substrate activation. (2R)-Hydroxypropylphosphonate partitioned between conversion to 2-oxopropylphosphonate and hydroxymethylphosphonate, with the latter in turn converted to phosphate and formate. Collectively, these results support a mechanism that proceeds by hydroperoxylation followed by a Criegee rearrangement.

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Section: Methodsmentioning

confidence: 99%

Hydroperoxylation by Hydroxyethylphosphonate Dioxygenase

2009

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“…These carbamates were hydrolyzed with 1 M hydrochloric acid. However, when the aryl moiety was acid sensitive we prepared the 2-(trimethylsilyl)ethyl carbamate, which was hydrolyzed with tetrabutylammonium fluoride . Due to decomposition of the aryl moiety, we were not able to isolate the desired product from the hydrolysis (tetrabutylammonium fluoride or iodotrimethylsilane 11 ) of the carbamate function in the 2-furylcyclopropyl derivative.…”

Section: Chemistrymentioning

confidence: 99%

trans-2-Aryl-N,N-dipropylcyclopropylamines: Synthesis and Interactions with 5-HT_1AReceptors

et al. 1996

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Twelve N,N-dipropyl-substituted derivatives of trans-2-arylcyclopropylamine have been prepared and assayed for their ability to displace [(3)H]-8-OH-DPAT from rat brain 5-HT(1A) receptors. The new derivatives include phenyl (7a), bromo- (7b) and fluorophenyl (7c-e), 2-methoxy-5-fluorophenyl (7h), and 2-hydroxy-5-fluorophenyl (7l) as well as trifluoromethylphenyl (7f) and 2,3-dichlorophenyl (7g) analogues. In the present series of compounds, electron-withdrawing substituents in the phenyl ring appear to decrease the affinity for 5-HT(1A) receptors. In contrast, electron-rich aryl groups, such as 2- or 3-thienyl (7j and 7k, respectively), provide compounds with high affinity. The additional bulk produced by the aromatic moiety in the 2-benzothienyl derivative 7i appears to be detrimental to 5-HT(1A) receptor affinity. The racemic mixtures of the interesting 7j and 7l were resolved into the enantiomers; 7j and 7l exhibited a high enantiomeric 5-HT(1A) receptor affinity ratio (75-fold and 100-fold, respectively). The enantiomers of 7j and 7l were evaluated in vivo by use of biochemical and behavioral tests in rats. Compound (1R,2R)-7j behaved as a partial agonist whereas (1R,2S)-7l appeared as an efficacious 5-HT(1A) receptor agonist, stimulating both autoreceptors and postsynaptic receptors.

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Formation of Nitriles, Carboxylic Acids, and Derivatives by Oxidation, Substitution, and Addition

Larock

Yao

2017

Comprehensive Organic Transformations

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Alkanes Arenes Alkenes Dienes Alkynes Alkyl Halides Amines Imines and Derivatives Azides Nitro Compounds Nitrothioalkenes Ethers Sulfides Alcohols Diols Amino Alcohols Azido Alcohols Phenols Aldehydes and Derivatives Ketones Hemiacetals and Lactols Acetals Carboxylic Acids Esters Amides Nitriles

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Synthesis of ammonium analogs of carbocationic intermediates in the conversion of presqualene diphosphate to squalene

Cited by 17 publications

References 5 publications

Hydroperoxylation by Hydroxyethylphosphonate Dioxygenase

Hydroperoxylation by Hydroxyethylphosphonate Dioxygenase

trans-2-Aryl-N,N-dipropylcyclopropylamines: Synthesis and Interactions with 5-HT_1AReceptors

Formation of Nitriles, Carboxylic Acids, and Derivatives by Oxidation, Substitution, and Addition

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Synthesis of ammonium analogs of carbocationic intermediates in the conversion of presqualene diphosphate to squalene

Cited by 17 publications

References 5 publications

Hydroperoxylation by Hydroxyethylphosphonate Dioxygenase

Hydroperoxylation by Hydroxyethylphosphonate Dioxygenase

trans-2-Aryl-N,N-dipropylcyclopropylamines: Synthesis and Interactions with 5-HT1AReceptors

Formation of Nitriles, Carboxylic Acids, and Derivatives by Oxidation, Substitution, and Addition

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About

trans-2-Aryl-N,N-dipropylcyclopropylamines: Synthesis and Interactions with 5-HT_1AReceptors