A new approach to the synthesis of lactams of muramic, isomuramic and normuramic acids via intramolecular O-alkylation: Stereochemical features of the intramolecular nucleophilic substitution

Pertel, Sergey S.; Seryi, Sergey A.; Kakayan, Elena S.

doi:10.1016/j.tet.2018.07.051

Cited by 1 publication

(1 citation statement)

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“…In nucleophilic substitution, an electron-rich nucleophile attacks an electron-poore lectrophile, replacing al eaving group. Despite being an elementaryr eaction, challenges remain in predictings eemingly simple reactiono utcomes whether in biochemical pathways, [1] the design of cancert herapeutics, [2,3] the preparation of challengingn atural products and pharmaceuticals, [4,5] the development of next-generation alkylation technologies, [6,7] or in understandingt he mechanism of endogenous alkylators. For example, S-Adenosyl methionine (SAM) [8][9][10] is ac ofactor that regulates as eries of biochemical transformations via transfer of the methyl group located on a positivelyc harged sulfur atom (Scheme S1).…”

Section: Introductionmentioning

confidence: 99%

Not‐So‐Innocent Anions Determine the Mechanism of Cationic Alkylators

Taimoory

Cataldo

Schäfer

et al. 2021

Chemistry A European J

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Alkylating reagents based on thioimidazolium ionic liquids were synthesized and the influence of the anion on the alkylation reaction mechanism explored in detail using both experimental and computational methods. Thioimidazolium cations transfer alkyl substituents to nucleophiles, however the reaction rate was highly dependent on anion identity, demonstrating that the anion is not innocent in the mechanism. Detailed analysis of the computationally‐derived potential energy surfaces associated with possible mechanisms indicated that this dependence arises from a combination of anion induced electronic, steric and coordinating effects, with highly nucleophilic anions catalyzing a 2‐step process while highly non‐nucleophilic, delocalized anions favor a 1‐step reaction. This work also confirms the presence of ion‐pairs and aggregates in solution thus supporting anion‐induced control over the reaction rate and mechanism. These findings provide new insight into an old reaction allowing for better design of cationic alkylators in synthesis, gene expression, polymer science, and protein chemistry applications.

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