Carbonyldiimidazole-Mediated Lossen Rearrangement

Dubé, Pascal; Nathel, Noah F. Fine; Vetelino, Michael G.; Couturier, Michel; Aboussafy, Claude Larrivée; Pichette, Simon; Jorgensen, Matthew L.; Hardink, Mark

doi:10.1021/ol9023387

Cited by 152 publications

(58 citation statements)

References 37 publications

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“…We found that the desired product could be synthesized by nucleophilic addition of benzylamine to 1,4,2-dioxazol-5-one, 8 (Scheme 2). 39 The reaction was indeed completely O -selective, affording 6a as the sole product in high yield (88%). Encouraged by this result, intermediate 8 was reacted with a variety of amines to provide carbamate prodrugs 6a - l (Scheme 2).…”

Section: Resultsmentioning

confidence: 90%

Targeting Botulinum A Cellular Toxicity: A Prodrug Approach

et al. 2013

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The botulinum neurotoxin light chain (LC) protease has become an important therapeutic target for post-exposure treatment of botulism. Hydroxamic acid based small molecules have proven to be potent inhibitors of LC/A with nanomolar Ki values, yet, they lack cellular activity conceivably due to low membrane permeability. To overcome this potential liability, we investigated two prodrug strategies, 1,4,2-dioxazole and carbamate, based on our 1- adamantylacetohydroxamic acid scaffold. The 1,4,2-dioxazole prodrug did not demonstrate cellular activity, however, carbamates exhibited cellular potency with the most active compound displaying an EC50 value of 20 μM. Cellular trafficking studies were conducted using a “fluorescently silent” prodrug that remained in this state until cellular uptake was complete, which allowed for visualization of the drug’s release inside neuronal cells. In sum, this research sets the stage for future studies leveraging the specific targeting and delivery of these prodrugs, as well as other antibotulinum agents, into neuronal cells.

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Section: Resultsmentioning

confidence: 90%

Targeting Botulinum A Cellular Toxicity: A Prodrug Approach

et al. 2013

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“…A most recent method for the synthesis of carbamates 6 through the reaction of hydroxamic acids 163 with an alcohol 5 using carbonyl diimidazole (CDI) through Lossen rearrangement was reported by Dube and coworkers (Scheme 145) [210]. …”

Section: 7c Lossen Rearrangementmentioning

confidence: 99%

Recent Developments on the Carbamation of Amines

Chaturvedi

2011

COC

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Organic carbamates represent an important class of compounds showing various interesting properties. They find wide utility in various areas as pharmaceuticals, agrochemicals (pesticides, herbicides, insecticides, fungicides etc.), intermediates in organic synthesis, protection of amino group in peptide chemistry, and as linker in combinatorial chemistry etc. Classical synthesis of carbamates involves use of harmful reagents such as phosgene, its derivatives and carbon monoxide. Recently, various kinds of synthetic methods have been developed for the synthesis of organic carbamates. In the present review, I would like to highlight the recent developments on the synthesis of organic carbamates using variety of reagents.

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“…Alternatively, the Lossen rearrangement provides access to isocyanates under relatively mild conditions. To date, several synthetic methods have been developed for the synthesis of ureas through Lossen rearrangement, for example, phosgene and its derivatives such as triphosgene [7] are widely used reagents for synthesis of ureas; together with chloroformates, [8] cyanuric chloride, [9] 1,1'-carbonyldiimidazole, [10] 1-propanephosphonic acid cyclic anhydride (T3P), [11] N,N'-dicyclohexylcarbodiimide, [12] Nbenzyl-N'-(3-dimethylaminopropyl)carbodiimide, [13] Zr(IV)-catalyst, [14] Pd-catalyzed [15] and 2-chloro-1-methylpyridinuim iodide. [16] On the other hand, Boc-Oxyma (I, Ethyl 2-(tertbutoxycarbonyloxyimino)-2-cyanoacetate, Figure 1) Figure 1.…”

Section: Introductionmentioning

confidence: 99%

Ethyl 2‐(tert‐Butoxycarbonyloxyimino)‐2‐cyanoacetate (Boc‐Oxyma): An Efficient Reagent for the Racemization Free Synthesis of Ureas, Carbamates and Thiocarbamates via Lossen Rearrangement

et al. 2016

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Boc-Oxyma (Ethyl 2-(tert-butoxycarbonyloxyimino)-2-cyanoacetate) has been reported previously as an efficient coupling reagent for the synthesis of amides, peptides, esters, thioesters and hydroxamic acids. It is known for its excellent racemization suppression capability, and also as an environment friendly reagent as it generates only Oxyma as solid byproduct that can be recovered easily and recycled for the synthesis of the same reagent. In this update, we report a simple, efficient, environment friendly, chemoselective and racemization free method for the synthesis of ureas, carbamates and thiocarbamates from hydroxamic acids via Lossen rearrangement by using Boc-Oxyma. We have achieved racemization free di-and tripeptidyl ureas with very good yield by using this protocol. A rigorous mechanistic investigation is also incorporated.

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Carbonyldiimidazole-Mediated Lossen Rearrangement

Cited by 152 publications

References 37 publications

Targeting Botulinum A Cellular Toxicity: A Prodrug Approach

Targeting Botulinum A Cellular Toxicity: A Prodrug Approach

Recent Developments on the Carbamation of Amines

Ethyl 2‐(tert‐Butoxycarbonyloxyimino)‐2‐cyanoacetate (Boc‐Oxyma): An Efficient Reagent for the Racemization Free Synthesis of Ureas, Carbamates and Thiocarbamates via Lossen Rearrangement

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