Naslov
Ferrocenoyl-Purines: Regioselective Synthesis and Acylation Mechanism

Autori
Toma, Mateja ; Filipović, Alma ; Lapić, Jasmina ; Djaković, Senka ; Šakić, Davor ; Vrček, Valerije

Vrsta, podvrsta i kategorija rada
Sažeci sa skupova, sažetak, znanstveni

Izvornik
Computational Chemistry Day - Book of Abstracts / Babić, Darko - Zagreb : Prirodoslovno-matematički fakultet Sveučilišta u Zagrebu, 2018, 29-29

ISBN
978-953-6076-45-1

Skup
Computational Chemistry Day 2018

Mjesto i datum
Zagreb, Hrvatska, 12.05.2018

Vrsta sudjelovanja
Poster

Vrsta recenzije
Domaća recenzija

Ključne riječi
ferrocene, nucleobase, DFT, acylation mechanism

Sažetak
Ferrocene nucleobase conjugates are organometallic compounds where the ferrocene moiety is covalently linked through various "linkers" with heterocyclic nucleobases. [1] The synthesis of ferrocenoyl-purines is based on acylation [2] of purine anions with ferrocenoyl-chloride and in most cases both N7- and N9- isomers were detected by NMR spectroscopy and isolated. In this study we combined synthesis, NMR spectroscopy and quantum chemical calculations to investigate the steric effect of C6-substituent of purine anions on N9/N7 ferrocenoylation. It is found that N9/N7-regioisomers ratio is dependent on the C6–substitution of the purine system. It is possible that the bulkier substituent at C6-position causes shielding of the N7 position which inhibits N7-acylation of purine anions. When adenine anion was ferrocenoylated, the N9-isomer was the major product (79%). For N6-methyl adenine and N6, N6-dimethyl adenine the acylation resulted in increased yield of N9-isomer, leading to reaction regiospecificity in case of the N(Boc)2-adenine where only N9-regioisemer was formed. The ratio of N9 : N7 isomers, determined quantitatively by integration of signals in 1H NMR spectra of the reaction mixture, is strongly correlated to the effective (Charton’s) and calculated multidimensional (Sterimol) steric parameters of the C6-substituent. Finally, quantum-chemical calculations suggest that the barrier for the N7-isomer formation is higher than the corresponding barrier for N9-isomer formation. The calculated energy barrier difference for N7 and N9 –acylation reaction is in correlation with N9/N7 product ratio andsteric parameters of C6-substituents, which nicely supports our experimental results . All structures were optimized with the B3LYP functional and the standard 6-31+G(d) basis set was used for geometry optimizations and frequency calculations.

Izvorni jezik
Engleski

Znanstvena područja
Kemija, Farmacija

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