Stable enol esters from N-tert-butyl-5-methylisoxazolium perchlorate

Woodward, R. B.; Woodman, D. J.

doi:10.1021/ja01007a060

Cited by 23 publications

(6 citation statements)

References 2 publications

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“…The key intermediate N -(3-iodobenzyl)- N′ -(3-carbonyl-quinoline)-guanidine ( 1 ) was prepared using four different routes by reaction of several activated esters of 3-quinoline carboxylic acid with 4 . The first attempts involving the condensation of 4 with the corresponding methyl ester of 3-quinoline carboxylic acid or with a crotonamide intermediate obtained with N - tert -butyl-5-methylisoxazolium perchlorate (NBI) provided 1 in 35−37% yield. − To find a better procedure, we have also used the N , N ′-carbonyldiimidazole (CDI) or N -hydroxysuccinimide as carboxylate activating agents . The reactions of resulting activated esters with 4 showed a significant increase in reactivity and compound 1 was isolated in 59.5−61.5% yield.…”

Section: Resultsmentioning

confidence: 99%

Chemical Delivery System of Metaiodobenzylguanidine (MIBG) to the Central Nervous System

et al. 2010

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The aim of the present investigation was to apply a chemical delivery system (CDS) to MIBG (4) with the purpose of delivering this drug to the CNS. Compound 4 has been linked to a 1,4-dihydroquinoline moiety in order to achieve its CNS penetration, and here we report the synthesis to link 4 to the chemical delivery system and the radiosynthesis with carbon-11 of the "CDS-4 entity". After iv injection into rats of the [(11)C]CDS-4, the follow-up study of the radioactivity distribution in blood samples and brain homogenates and the analysis by HPLC and LC-MS/MS have confirmed the release of 4 into the CNS.

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Section: Resultsmentioning

confidence: 99%

Chemical Delivery System of Metaiodobenzylguanidine (MIBG) to the Central Nervous System

et al. 2010

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“…These findings provide proof-of-principle for the notion that fairly reactive functional groups can be engineered and employed for the successful development of covalent inhibitors targeting carboxylic acids with attenuated nucleophilic potency in protein pockets. For WRK-type isoxazolium salts this fine-tuning can be achieved by varying the steric demand and electronic properties of the heterocycle substituents (Woodman and Davidson, 1970;Woodward and Woodman, 1968;. However, reactivity may also translate into selectivity.…”

Section: Discussionmentioning

confidence: 99%

Covalent Protein Labeling at Glutamic Acids

Martín‐Gago

Fansa

Winzker

et al. 2017

Cell Chemical Biology

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Covalent labeling of amino acids in proteins by reactive small molecules, in particular at cysteine SH and lysine NH groups, is a powerful approach to identify and characterize proteins and their functions. However, for the less-reactive carboxylic acids present in Asp and Glu, hardly any methodology is available. Employing the lipoprotein binding chaperone PDE6δ as an example, we demonstrate that incorporation of isoxazolium salts that resemble the structure and reactivity of Woodward's reagent K into protein ligands provides a novel method for selective covalent targeting of binding site carboxylic acids in whole proteomes. Covalent adduct formation occurs via rapid formation of enol esters and the covalent bond is stable even in the presence of strong nucleophiles. This new method promises to open up hitherto unexplored opportunities for chemical biology research.

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“…186 To address this issue, a bulky substituent was installed on the nitrogen atom to suppress such uninvited rearrangement. 190,191 The enol ester derived from 39-1b was sufficiently stable for storage and resistant to rearrangement. However, the formation of enol esters from 39-1b was relatively slow and suffered from side reactions in polar solvents.…”

Section: Woodward Reagentsmentioning

confidence: 99%