engleski

Ferrocenoyl-Adenines: Substituent Effects on Regioselective Acylation

A series of N6-substituted adenine-ferrocene conjugates were prepared and the reaction mechanism underlying the synthesis was explored. The SN2-like reaction between ferrocenoyl chloride and adenine anions is a regioselective process in which the product ratio (N7/N9-ferrocenoyl isomers) is governed by the steric property of the substituent at the N6-position. Steric effects were evaluated by using Charton (empirical), Sterimol (computational), andSambVca %VBur (computational) parameters. Sterimol and SambVca parameters were calculated using new web-page implementation, with integrated Boltzmann averaging for conformer structures libraries [1]. The bulky substituents may shield the proximal N7 region of space, which prevents the approach of an electrophile towards the N7 atom. As a consequence, the formation of N7-isomer is kinetically less feasible process, i.e. the corresponding transition state structure increases in relative energy (compared to the formation of the N9- isomer). In cases where the steric hindrance is negligible, the electronic effect of the N6- substituent is prevailing. That was supported by calculations of Fukui functions and molecular orbital coefficients. Both descriptors indicated that the N7 atom was more nucleophilic than its N9- counterpart in all adenine anion derivatives. We demonstrated that selected substituents may shift the acylation of purines from regioselective to regiospecific mode.

ferrocene, nucleobase, regoiselective synthesis, DFT

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