Premium
1,1′‐Bis(thymine)ferrocene Nucleoside: Synthesis and Study of Its Stereoselective Formation
Author(s) -
Anisimov Iurii,
Saloman Sebastian,
Hildebrandt Alexander,
Lang Heinrich,
Trzybiński Damian,
Woźniak Krzysztof,
Šakić Davor,
Vrček Valerije,
Kowalski Konrad
Publication year - 2017
Publication title -
chempluschem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.801
H-Index - 61
ISSN - 2192-6506
DOI - 10.1002/cplu.201700215
Subject(s) - chemistry , thymine , ferrocene , adduct , nucleoside , stereoselectivity , redox , yield (engineering) , stereochemistry , medicinal chemistry , organic chemistry , electrochemistry , catalysis , dna , biochemistry , materials science , electrode , metallurgy
Abstract The synthesis of 1,1′‐bis(thymine)ferrocene nucleoside is reported. This nucleoside was obtained in a two‐step synthetic methodology including a Michael addition reaction of 1,1′‐bis(3‐chloropropionyl)ferrocene with thymine to afford the bis(thymine) adduct in 44 % yield. In the second step, the two prochiral carbonyl functionalities in the Michael adduct were reduced to hydroxyl groups with sodium borohydride. This apparently straightforward reaction proceeds in a highly stereoselective fashion to yield the title ferrocenyl nucleoside as a racemic mixture that consists of the R , R and the S , S isomers. The absolute configuration of the chiral carbon atoms in the nucleoside was assigned on the basis of single‐crystal X‐ray diffraction analysis of the methyl derivative. Furthermore, the mechanism of reduction of the bis(thymine) adduct was investigated by using DFT calculations. The two critical minima, pre‐reactive complex, and semi‐reduced intermediate, as well as two corresponding transition states were located to support the observed stereoselectivity. The redox properties of 1,1′‐bis(thymine)ferrocene nucleoside, its precursor, and congeners were investigated using cyclic voltammetry. For the title compound a reversible redox process was found at a low potential of −30 mV versus FcH/FcH + (FcH=Fe(η 5 ‐C 5 H 5 ) 2 ) as the reference redox couple.