Molecules 2011, 16(6), 5113-5129; doi:10.3390/molecules16065113

Methoxymethyl (MOM) Group Nitrogen Protection of Pyrimidines Bearing C-6 Acyclic Side-Chains

1,* email, 1, 1, 2,3, 2,3,4, 5, 6 and 1,* email
Received: 26 May 2011; in revised form: 15 June 2011 / Accepted: 16 June 2011 / Published: 20 June 2011
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Abstract: Novel N-methoxymethylated (MOM) pyrimidine (4-13) and pyrimidine-2,4-diones (15-17) nucleoside mimetics in which an isobutyl side-chain is attached at the C-6 position of the pyrimidine moiety were synthesized. Synthetic methods via O-persilylated or N-anionic uracil derivatives have been evaluated for the synthesis of N-1- and/or N-3-MOM pyrimidine derivatives with C-6 acyclic side-chains. A synthetic approach using an activated N-anionic pyrimidine derivative afforded the desired N,N-1,3-diMOM and N-1-MOM pyrimidines 4 and 5 in good yield. Introduction of fluorine into the side-chain was performed with DAST as the fluorinating reagent to give a N,N-1,3-diMOM pyrimidine 13 with a 1-fluoro-3-hydroxyisobutyl moiety at C-6. Conformational study of the monotritylated N-1-MOM pyrimidine 12 by the use of the NOE experiments revealed the predominant conformation of the compound to be one where the hydroxymethyl group in the C-6 side-chain is close to the N-1-MOM moiety, while the OMTr is in proximity to the CH3-5 group. Contrary to this no NOE enhancements between the N-1-MOM group and hydroxymethyl or fluoromethyl protons in 13 were observed, which suggested a nonrestricted rotation along the C-6 side-chain. Fluorinated N,N-1,3-diMOM pyrimidine 13 emerged as a model compound for development of tracer molecules for non-invasive imaging of gene expression using positron emission tomography (PET).
Keywords: N-methoxymethyl protecting group; C-6 isobutyl pyrimidine derivatives; N-1 and N-3 regioisomers; NOE experiments; positron emission tomography (PET)
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MDPI and ACS Style

Kraljević, T.G.; Petrović, M.; Krištafor, S.; Makuc, D.; Plavec, J.; Ross, T.L.; Ametamey, S.M.; Raić-Malić, S. Methoxymethyl (MOM) Group Nitrogen Protection of Pyrimidines Bearing C-6 Acyclic Side-Chains. Molecules 2011, 16, 5113-5129.

AMA Style

Kraljević TG, Petrović M, Krištafor S, Makuc D, Plavec J, Ross TL, Ametamey SM, Raić-Malić S. Methoxymethyl (MOM) Group Nitrogen Protection of Pyrimidines Bearing C-6 Acyclic Side-Chains. Molecules. 2011; 16(6):5113-5129.

Chicago/Turabian Style

Kraljević, Tatjana Gazivoda; Petrović, Martina; Krištafor, Svjetlana; Makuc, Damjan; Plavec, Janez; Ross, Tobias L.; Ametamey, Simon M.; Raić-Malić, Silvana. 2011. "Methoxymethyl (MOM) Group Nitrogen Protection of Pyrimidines Bearing C-6 Acyclic Side-Chains." Molecules 16, no. 6: 5113-5129.

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