Naslov
Ferrocenoyl-adenines: substituent effects on regioselective acylation

Autori
Toma, Mateja ; Zubčić, Gabrijel ; Lapić, Jasmina ; Djaković, Senka ; Šakić, Davor ; Vrček, Valerije

Izvornik
Beilstein journal of organic chemistry (2195-951X) 18 (2022); 1270-1277

Vrsta, podvrsta i kategorija rada
Radovi u časopisima, članak, znanstveni

Ključne riječi
DFT ; ferrocene ; nucleophilicity ; purine ; steric effect

Sažetak
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) and Sterimol (computational) parameters. 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.

Izvorni jezik
Engleski

Znanstvena područja
Kemija, Farmacija

POVEZANOST RADA