Gas-phase basicities of .beta.-lactams and azetidines. Cyclization effects. An experimental and theoretical study

Abboud, José‐Luis M.; Canada, T.; Homan, H.; Notario, Rafael; Cativiela, C.; Dı́az-de-Villegas, Marı́a D.; Bordeje, M. C.; Mó, Otília; Yáñez, Manuel

doi:10.1021/ja00038a040

Cited by 51 publications

(56 citation statements)

References 8 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The value provided is 61 kJ mol −1 lower than that of the parent molecule, azetidine, in conspicuous contrast with the expectation that the introduction of an N-methyl group would increase the basicity somewhat [49]. The literature reference provided in the NIST tables [37] does not provide data by which to assess the proton affinity of N-methylazetidine [54].…”

Section: Alicyclic Compoundsmentioning

confidence: 94%

The proton affinities of saturated and unsaturated heterocyclic molecules

Kabli

Beelen

Ingemann

et al. 2006

International Journal of Mass Spectrometry

View full text Add to dashboard Cite

Section: Alicyclic Compoundsmentioning

confidence: 94%

The proton affinities of saturated and unsaturated heterocyclic molecules

Kabli

Beelen

Ingemann

et al. 2006

International Journal of Mass Spectrometry

View full text Add to dashboard Cite

“…Protonation in O (4) indicates that the reactivity of staurosporine derivatives may be compared to the lactam rings, where the proton is located at carbonyl. 30 Thus, on the basis of these two possible protonation sites and PA values, two main competitive fragmentation pathways were suggested from the protonated molecule of the staurosporine derivatives (for fragment ions spectra see Figure 4). The most stable protonated specie occurs when the proton take place at N(2) ( Table 2) and, pathway A ( Figure 5) triggers by a concerted mechanism.…”

Section: Resultsmentioning

confidence: 99%

Systematic UPLC-ESI-MS/MS study on the occurrence of staurosporine and derivatives in associated marine microorganisms from Eudistoma vannamei

Andréo¹,

Jimenez²,

Siebra³

et al. 2012

J. Braz. Chem. Soc.

View full text Add to dashboard Cite

O estudo fitoquímico do invertebrado marinho Eudistoma vannamei levou ao isolamento de derivados do alcalóide estaurosporina, que apresentaram uma potente atividade citotóxica contra linhagens de células humanas de câncer. A ocorrência destes alcalóides pode ser correlacionada a presença de microorganismos associados ao animal, como por exemplo bactérias do gênero Streptomyces. Visando confirmar essa hipótese, precedeu-se o isolamento e cultivo dos microrganismos associados com E. vannamei (84 cepas isoladas). Estudos sistemáticos das reações de fragmentação da estaurosporina e derivados, apoiados pela química computacional, permitiram definir os principais padrões de fragmentação. Esses padrões foram utilizados em análises exploratórias por LC-MS/MS visando pesquisar a presença de derivados de estaurosporinas nos microrganismos isolados. Esse procedimento permitiu identificar estaurosporina em uma espécie de Streptomyces, contudo não com o mesmo padrão de oxidação da molécula ativa isolada no extrato da Ascídia. Finalmente, o extrato dessa cepa mostrou também significativa atividade citotóxica contra linhagens de câncer.Former bioactivity-guided analysis of the marine invertebrate Eudistoma vannamei led to the isolation of staurosporine derivatives, which revealed strong cytotoxic activity against several human cancer cell lines. The occurrence of such alkaloids in E. vannamei may be correlated to the presence of associated biota, such as Streptomyces bacteria. In agreement to this hypothesis, marine microorganisms associated with E. vannamei were recovered and cultured, leading to a total of 84 isolated bacterial strains. Gas phase fragmentation reactions of staurosporine and derivatives were systematically studied and the analyzed results further supported by computational chemistry studies. The resulting fragment patterns were used to search for the presence of different derivatives in extracts of isolated microorganisms, thereby using LC-MS/MS analysis in MRM mode. These results evidenced that one isolated Streptomyces sp. was able to generate staurosporine, while none of the hydroxy-7-oxo derivatives were detected. Finally, significant cytotoxic activity against human cancer lines was observed for one of the extracts.

show abstract

“…Theoretical studies show that b-lactams are weaker bases, in the gas phase, than acyclic amides [1]. The attenuation of basicity upon cyclization is stronger than that found for cyclic ketones of similar size due to the existence of a negative hyperconjugation effect that is present in b-lactams but not in cyclic ketones.…”

Section: Computational Chemistrymentioning

confidence: 93%

The Chemistry of 2‐Azetidinones (β‐Lactams)

Alcaide¹,

Almendros²,

Luna³

2011

Modern Heterocyclic Chemistry

View full text Add to dashboard Cite

The large number of recent reports on b-lactam chemistry demonstrates the increasing interest in this important class of compounds. Monocyclic b-lactams frequently serve as precursors for the synthesis of classical bicyclic b-lactam antibiotics. The cyclic 2-azetidinone skeleton has been extensively used as a template on which to build the heterocyclic structure fused to the four-membered ring, using the chirality and functionalization of the b-lactam nucleus as a stereocontrolling element. The discovery of nonclassical b-lactam antibiotics, such as monobactams and nocardicins, coupled with ever-growing new applications such as enzyme inhibition has triggered a renewed interest in the building of new monocyclic b-lactam derivatives. Besides the utility of b-lactams as biologically active agents, they are used as intermediates in a-and b-amino acid synthesis, as well as building blocks for alkaloids, heterocycles, taxoids and other types of compounds of biological and medicinal interest. Physicochemical Data Computational ChemistryTheoretical studies show that b-lactams are weaker bases, in the gas phase, than acyclic amides [1]. The attenuation of basicity upon cyclization is stronger than that found for cyclic ketones of similar size due to the existence of a negative hyperconjugation effect that is present in b-lactams but not in cyclic ketones. Ab initio calculations indicate that both b-lactams and acyclic amides are oxygen bases, but the gap between the oxygen and nitrogen intrinsic basicities is much smaller in the former due to the aforementioned cyclization effects. This decrease of the oxygen Modern Heterocyclic Chemistry, First Edition. Edited

show abstract

Gas-phase basicities of .beta.-lactams and azetidines. Cyclization effects. An experimental and theoretical study

Cited by 51 publications

References 8 publications

The proton affinities of saturated and unsaturated heterocyclic molecules

The proton affinities of saturated and unsaturated heterocyclic molecules

Systematic UPLC-ESI-MS/MS study on the occurrence of staurosporine and derivatives in associated marine microorganisms from Eudistoma vannamei

The Chemistry of 2‐Azetidinones (β‐Lactams)

Contact Info

Product

Resources

About