title: Large scale synthesis of 2'-amino-LNA thymine and 5-methylcytosine nucleosides.
abstract: Thymine intermediate 17 has been synthesized on a multigram scale (50 g, 70 mmol) from starting sugar 1 in 15 steps in an overall yield of 73%, with only 5 purification steps. The key thymine intermediate 18 was obtained from 17 in a single step in 96% yield, whereas the key 5-methylcytosine intermediate 20 was obtained from 17 in 2 steps in 58% yield. This highly efficient large scale route necessitates only 2 and 3 novel steps to obtain N2'-functionalized thymine and 5-methylcytosine amino-LNA phosphoramidites from these key intermediates, respectively.
authors.affiliation: Nucleic Acid Center, Department of Physics, Chemistry and Pharmacy, University of Southern Denmark, 5230 Odense M, Denmark.
authors.forename: Andreas Stahl
authors.initials: AS
authors.lastname: Madsen
authors.forename: Anna Søndergaard
authors.initials: AS
authors.lastname: Jørgensen
authors.forename: Troels Bundgaard
authors.initials: TB
authors.lastname: Jensen
authors.forename: Jesper
authors.initials: J
authors.lastname: Wengel
mesh_terms: D044503:5-Methylcytosine / Q000138:chemical synthesis* / Q000737:chemistry; D015394:Molecular Structure; D009705:Nucleosides / Q000138:chemical synthesis* / Q000737:chemistry; D009943:Organophosphorus Compounds / Q000737:chemistry*; D013938:Thymidine Monophosphate / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry; D013941:Thymine / Q000138:chemical synthesis* / Q000737:chemistry
chemical_list: C520121:7-(2-cyanoethoxy(diisopropylamino)phosphinoxy)-1-(4,4'-dimethoxytrityloxymethyl)-5-(9'-fluorenylmethoxycarbonyl)-3-(thymin-1-yl)-2-oxa-5-azabicyclo(2.2.1)heptane; D009705:Nucleosides; D009943:Organophosphorus Compounds; C434331:phosphoramidite; D013938:Thymidine Monophosphate; D044503:5-Methylcytosine; D013941:Thymine