title: Methoxymethyl (MOM) group nitrogen protection of pyrimidines bearing C-6 acyclic side-chains.
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 CH(3)-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).
authors.affiliation: Department of Organic Chemistry, Faculty of Chemical Engineering and Technology, University of Zagreb, Marulićev trg 20, Zagreb, Croatia. tatjana.gazivoda@fkit.hr
authors.forename: Tatjana Gazivoda
authors.initials: TG
authors.lastname: Kraljević
authors.forename: Martina
authors.initials: M
authors.lastname: Petrović
authors.forename: Svjetlana
authors.initials: S
authors.lastname: Krištafor
authors.forename: Damjan
authors.initials: D
authors.lastname: Makuc
authors.forename: Janez
authors.initials: J
authors.lastname: Plavec
authors.forename: Tobias L
authors.initials: TL
authors.lastname: Ross
authors.forename: Simon M
authors.initials: SM
authors.lastname: Ametamey
authors.forename: Silvana
authors.initials: S
authors.lastname: Raić-Malić
mesh_terms: D002244:Carbon / Q000737:chemistry*; D009584:Nitrogen / Q000737:chemistry* / Q000378:metabolism; D011743:Pyrimidines / Q000138:chemical synthesis / Q000737:chemistry*
chemical_list: D011743:Pyrimidines; D002244:Carbon; C030986:pyrimidine; D009584:Nitrogen