Methoxymethyl (MOM) Group Nitrogen Protection of Pyrimidines Bearing C-6 Acyclic Side-Chains
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...
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| Format: | Article |
| Language: | English |
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MDPI AG
2011-06-01
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| Series: | Molecules |
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| Online Access: | http://www.mdpi.com/1420-3049/16/6/5113/ |
| _version_ | 1811300836675944448 |
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| author | Janez Plavec Tobias L. Ross Simon M. Ametamey Silvana Raić-Malić Damjan Makuc Martina Petrović Svjetlana Krištafor Tatjana Gazivoda Kraljević |
| author_facet | Janez Plavec Tobias L. Ross Simon M. Ametamey Silvana Raić-Malić Damjan Makuc Martina Petrović Svjetlana Krištafor Tatjana Gazivoda Kraljević |
| author_sort | Janez Plavec |
| collection | DOAJ |
| description | 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). |
| first_indexed | 2024-04-13T06:58:08Z |
| format | Article |
| id | doaj.art-c53cc0a05b4d4a2481d2e52523c339c8 |
| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-04-13T06:58:08Z |
| publishDate | 2011-06-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Molecules |
| spelling | doaj.art-c53cc0a05b4d4a2481d2e52523c339c82022-12-22T02:57:12ZengMDPI AGMolecules1420-30492011-06-011665113512910.3390/molecules16065113Methoxymethyl (MOM) Group Nitrogen Protection of Pyrimidines Bearing C-6 Acyclic Side-ChainsJanez PlavecTobias L. RossSimon M. AmetameySilvana Raić-MalićDamjan MakucMartina PetrovićSvjetlana KrištaforTatjana Gazivoda KraljevićNovel 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).http://www.mdpi.com/1420-3049/16/6/5113/N-methoxymethyl protecting groupC-6 isobutyl pyrimidine derivativesN-1 and N-3 regioisomersNOE experimentspositron emission tomography (PET) |
| spellingShingle | Janez Plavec Tobias L. Ross Simon M. Ametamey Silvana Raić-Malić Damjan Makuc Martina Petrović Svjetlana Krištafor Tatjana Gazivoda Kraljević Methoxymethyl (MOM) Group Nitrogen Protection of Pyrimidines Bearing C-6 Acyclic Side-Chains Molecules N-methoxymethyl protecting group C-6 isobutyl pyrimidine derivatives N-1 and N-3 regioisomers NOE experiments positron emission tomography (PET) |
| title | Methoxymethyl (MOM) Group Nitrogen Protection of Pyrimidines Bearing C-6 Acyclic Side-Chains |
| title_full | Methoxymethyl (MOM) Group Nitrogen Protection of Pyrimidines Bearing C-6 Acyclic Side-Chains |
| title_fullStr | Methoxymethyl (MOM) Group Nitrogen Protection of Pyrimidines Bearing C-6 Acyclic Side-Chains |
| title_full_unstemmed | Methoxymethyl (MOM) Group Nitrogen Protection of Pyrimidines Bearing C-6 Acyclic Side-Chains |
| title_short | Methoxymethyl (MOM) Group Nitrogen Protection of Pyrimidines Bearing C-6 Acyclic Side-Chains |
| title_sort | methoxymethyl mom group nitrogen protection of pyrimidines bearing c 6 acyclic side chains |
| topic | N-methoxymethyl protecting group C-6 isobutyl pyrimidine derivatives N-1 and N-3 regioisomers NOE experiments positron emission tomography (PET) |
| url | http://www.mdpi.com/1420-3049/16/6/5113/ |
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