Competing fragmentation processes of β‐substituted propanoate ions upon collision‐induced dissociation

LeBlanc, Luc M.; Powers, Sean W.; Grossert, J. Stuart; White, Robert L.

doi:10.1002/rcm.7699

Cited by 5 publications

(6 citation statements)

References 47 publications

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“…In the hydroxy anion of 16c , the double bond between N(a) and N(b) is appropriately positioned for the release of dinitrogen upon the formation of a carbonyl at C(e) (Scheme D). This process is analogous to Grob fragmentation and the favorable decarboxylative elimination found in β‐substituted propanoate ions . The minor and major ions, at m / z 190 and 91 respectively, are consistent with subsequent losses of carbon monoxide and ethyl cyanoformate that occur with the formation of a benzyl anion.…”

Section: Resultssupporting

confidence: 56%

Regioselective N‐Alkylation of Ethyl 4‐Benzyloxy‐1,2,3‐triazolecarboxylate: A Useful Tool for the Synthesis of Carboxylic Acid Bioisosteres

Sainas

Pippione

Giraudo

et al. 2018

Journal of Heterocyclic Chem

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Acidic 4‐hydroxy‐1,2,3‐triazole is a proven bioisostere of acidic functions that has recently been used to replace the acidic moieties of biologically active leads. Straightforward chemical strategies for the synthesis of the three possible N‐alkylated 4‐hydroxy‐1,2,3‐triazole regioisomers have been designed and reported herein, by identifying the optimal conditions under which the alkylation of ethyl 4‐benzyloxy‐1,2,3‐triazolecarboxylate (compound 19) can be regiodirected to the triazole N(b) position and thus produce the only isomer that cannot be obtained via the cycloaddition reaction. Furthermore, an innovative platform for parallel synthesis, called Arachno and which has been patented by the authors' group, has been used to speed up the process, and an NMR study has been carried out to better understand the reactivity of compound 19 towards the N(b) position. A library of benzyloxy protected 4‐hydroxy‐1,2,3‐triazoles has been prepared using the two strategies: regiodirection for the N(b) and N(c) isomers and cycloaddition for the N(a) isomers; the processes are described herein. The three N‐alkylated regioisomer series have been characterized spectroscopically (NMR and MS). The subsequent catalytic hydrogenation of the 4‐benzyloxy protective group on the N‐alkylated‐4‐benzyloxy‐5‐ethoxycarbonyl‐1,2,3‐triazoles provided the corresponding substituted 4‐hydroxy‐1,2,3‐triazoles.

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Section: Resultssupporting

confidence: 56%

Regioselective N‐Alkylation of Ethyl 4‐Benzyloxy‐1,2,3‐triazolecarboxylate: A Useful Tool for the Synthesis of Carboxylic Acid Bioisosteres

Sainas

Pippione

Giraudo

et al. 2018

Journal of Heterocyclic Chem

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“…In principle, a third pathway involving carboxyl group abstraction of the α‐proton followed by elimination of cyanide is possible. Although a reasonable barrier for the α‐proton abstraction was indicated by previous computations (180–200 kJ mol −1 ), 39 a possible complementary ion (CH 2 =C(NH 2 )CO 2 − , m / z 86) was not detected…”

Section: Resultsmentioning

confidence: 69%

“…In addition to the sequential reactions described above, the three-bond separation of the carboxyl and nitrile groups in β-cyanoalanate (7a) indicated that cyanide (7c) formation by decarboxylative elimination 39,40 was also possible. The transition structure TS 7a-7c located in the computations showed a favorable antiperiplanar alignment of partially cleaved C α -CO 2 À and C β -CN bonds (Figure 5B); however, decarboxylative elimination required a slightly larger energy input than the loss of ammonia (Figure 5A).…”

Section: β-Cyanoalanate (7a)mentioning

confidence: 96%

Tandem mass spectrometry of homologous 3‐hydroxyfurazan and nitrile amino acids: Analysis of cooperative interactions and fragmentation processes

Grossert,

Crowell,

Boschi

et al. 2024

J Mass Spectrom

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The assignment of structure by tandem mass spectrometry (MS/MS) relies on the interpretation of the fragmentation behavior of gas‐phase ions. Mass spectra were acquired for a series of heterocyclic mimetics of acidic amino acids and a related series of nitrile amino acids. All amino acids were readily protonated or deprotonated by electrospray ionization (ESI), and distinctive fragmentation processes were observed when the ions were subjected to collision‐induced dissociation (CID). The deprotonated heterocycles showed bond cleavages of the 3‐hydroxyfurazan ring with formation of oxoisocyanate and the complementary deprotonated nitrile amino acid. Further fragmentation of the deprotonated nitrile amino acids was greatly dependent on the length of the alkyl nitrile side chain. Competing losses of CO2 versus HCN occurred from α‐cyanoglycinate (shortest chain), whereas water was lost from 2‐amino‐5‐cyanopentanoate (longest chain). Interestingly, loss of acrylonitrile by a McLafferty‐type fragmentation process was detected for 2‐amino‐4‐cyanobutanoate, and several competing processes were observed for β‐cyanoalanate. In one process, cyanide ion was formed either by consecutive losses of ammonia, carbon dioxide, and acetylene or by a one‐step decarboxylative elimination. In another, complementary ions were obtained from β‐cyanoalanate by loss of acetonitrile or HN=CHCO2H. Fragmentation of the protonated 3‐hydroxyfurazan and nitrile amino acids resulted in the cumulative loss (H2O + CO), a loss that is commonly observed for protonated aliphatic α‐amino acids. Overall, the distinct fragmentation behavior of the multifunctional 3‐hydroxyfurazan amino acids correlated with the charged site, whereas fragmentations of the deprotonated nitrile amino acids showed cooperative interactions between the nitrile and the carboxylate groups.

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“…The cyanoacetic acid ester synthesis 46 allowed the synthesis of β 2 -and β 2,2 -amino acids, 47 including alicyclic and heterocyclic β 2,2 -amino acids. 48,49 The application of this methodology to sugars allowed to convert sugar ditriflate 9β into compound 35 (Scheme 7), the first reported polyhydroxylated cycloalkane β 2,2 -amino acid derivative.…”

Section: Papermentioning

confidence: 99%

Stable d-xylose ditriflate in divergent syntheses of dihydroxy prolines, pyrrolidines, tetrahydrofuran-2-carboxylic acids, and cyclic β-amino acids

et al. 2022

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Competing fragmentation processes of β‐substituted propanoate ions upon collision‐induced dissociation

Cited by 5 publications

References 47 publications

Regioselective N‐Alkylation of Ethyl 4‐Benzyloxy‐1,2,3‐triazolecarboxylate: A Useful Tool for the Synthesis of Carboxylic Acid Bioisosteres

Regioselective N‐Alkylation of Ethyl 4‐Benzyloxy‐1,2,3‐triazolecarboxylate: A Useful Tool for the Synthesis of Carboxylic Acid Bioisosteres

Tandem mass spectrometry of homologous 3‐hydroxyfurazan and nitrile amino acids: Analysis of cooperative interactions and fragmentation processes

Stable d-xylose ditriflate in divergent syntheses of dihydroxy prolines, pyrrolidines, tetrahydrofuran-2-carboxylic acids, and cyclic β-amino acids

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