Synthesis of an asymmetrically substituted AZA crown ether as metal and amino acid binding site in DNA conjugates

Article abstract of DOI:10.1081/NCN-120022730

Crown ether 4 as a receptor core for protonated primary amines such as amino acids has been synthesized and incorporated into oligodeoxynucleotides as dangling ends.

Full text of DOI:10.1081/NCN-120022730

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Synthesis of an Asymmetrically Substituted AZA Crown
Ether as Metal and Amino Acid Binding Site in DNA
Conjugates
Stefan Vogel a c , Katja Rohr a , Otto Dahl b & Jesper Wengel a
a Nucleic Acid Center , Department of Chemistry , University of Southern Denmark , Odense
M, Denmark
b Department of Chemistry , University of Copenhagen , Copenhagen, Denmark
c Nucleic Acid Center , Department of Chemistry , University of Southern Denmark ,
Campusvej 55, DK-5230, Odense M, Denmark
Published online: 31 Aug 2006.
To cite this article: Stefan Vogel , Katja Rohr , Otto Dahl & Jesper Wengel (2003) Synthesis of an Asymmetrically Substituted
AZA Crown Ether as Metal and Amino Acid Binding Site in DNA Conjugates, Nucleosides, Nucleotides and Nucleic Acids, 22:5-8,
1039-1040, DOI: 10.1081/NCN-120022730
To link to this article: http://dx.doi.org/10.1081/NCN-120022730
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NUCLEOSIDES, NUCLEOTIDES & NUCLEIC ACIDS
Vol. 22, Nos. 5–8, pp. 1039–1040, 2003
Synthesis of an Asymmetrically Substituted AZA Crown
Ether as Metal and Amino Acid Binding Site in
DNA Conjugates
1
2
1
Stefan Vogel,1, Katja Rohr, Otto Dahl, and Jesper Wengel
*
1Nucleic Acid Center, Department of Chemistry, University of
Southern Denmark, Odense M, Denmark
2Department of Chemistry, University of Copenhagen,
Copenhagen, Denmark
ABSTRACT
Crown ether 4 as a receptor core for protonated primary amines such as amino
acids has been synthesized and incorporated into oligodeoxynucleotides as
dangling ends.
Key Words: Aza crown ether; Amino acid binding.
A very limited number of binding sites for organic molecules have been incorpo-
rated into oligonucleotides. Functionalised crown ethers have special interest in
terms of host-guest chemistry.[1] Their selectivity for metal cations of different sizes
and complexation of organic molecules such as amines and amino acids is a starting
point for promising applications. It is noteworthy that especially triaza crown ethers
show a remarkable affinity for protonated primary amines.[2]
*Correspondence: Stefan Vogel, Nucleic Acid Center, Department of Chemistry, University
of Southern Denmark, Campusvej 55, DK-5230 Odense M, Denmark; Fax: þ 45 66 15 87 80;
E-mail: snv@chem.sdu.dk.
1039
DOI: 10.1081/NCN-120022730
Copyright # 2003 by Marcel Dekker, Inc.
1525-7770 (Print); 1532-2335 (Online)
www.dekker.com

1040
Vogel et al.
Scheme 1. a) (PhCO)2O, EtOH, reflux, 90%; b) MsCl, pyridine, 80%; c) RNH2, NEt3,
MeCN, 70%; d) LiAlH4, THF, 90%; e) TsO(CH2)2O(CH2)2OTs, Na2CO3, MeCN, 50%;
f) NC(CH2)2OP(Cl)N(iPr)2, (iPr)2NEt, CH2Cl2, 50%.
We here report synthesis of an appropriately modified triaza crown ether
compatible with automated synthesis using the phosphoramidite approach.
Commercially available 1 was treated with benzoic anhydride and subsequently
mesylated to give building block 2. Treatment of 2 with 2-aminoethanol afforded
a diamide. Reduction of the diamide led to the triamine 3 suitable for subsequent
macrocyclization reaction.[3] Accordingly, treatment of the triamine 3 with diethy-
lene glycol ditosylate led to a macrocycle which was subsequently converted into
the phosphoramidite 4 (Sch. 1).
Compound 4 was successfully incorporated (monomer X) into two complemen-
tary 9-mer sequences [50-d(XCGT ATA GTG) and 30-d(XGMeCLA TLATL CAC,
MeCL and TL are LNA monomers). Data on the complexation behaviour with
amines and Tm values will be reported in due course.
ACKNOWLEDGMENTS
Financial support by the Deutsche Forschungsgemeinschaft and the Danish
National Research Foundation is gratefully acknowledged.
REFERENCES
1. Buschmann, H.J.; Mutihac, L.; Jansen, K. Complexation of some amine com-
pounds by macrocyclic receptors. J. Incl. Phenom. 2001, 39, 1.
2. Lehn, J.M. The [18]-N3O3 aza-oxa macrocycle: A selective receptor unit for pri-
mary ammonium cations. Tetrahedron Lett. 1980, 21, 1323.
3. Krakowiak, K.E.; Bradshaw, J.S.; Izatt, R.M.; Zamecka-Krakowiak, D.J. A
new building block method to synthesize symmetrical and asymmetrical per-
N-alkyl-substituted polyaza-crown compounds. J. Org. Chem. 1989, 54, 4061.