title: Improved synthesis of trinucleotide phosphoramidites and generation of randomized oligonucleotide libraries.
abstract: A new method to produce a set of 20 high quality trinucleotide phosphoramidites on a 5-10 g scale each was developed. The procedure starts with condensation reactions of P-components with N-acyl nucleosides, bearing the 3 '-hydroxyl function protected with 2-azidomethylbenzoyl, to give fully protected dinucleoside phosphates 13. Upon cleavage of dimethoxytrityl group from 13, dinucleoside phosphates 16 are initially transformed into trinucleoside diphosphates 19 and then the 2-azidomethylbenzoyl is selectively removed under neutral conditions to generate trinucleoside diphosphates 5 in excellent yield. Subsequent 3 '-phosphitylation affords target trinucleotide phosphoramidites 7. When mutagenic oligonucleotides are synthesized employing mixtures of building blocks 7 as well as following the new synthetic protocol, representative oligonucleotide libraries are generated in good yields.
authors.affiliation: Department of Pharmaceutical Chemistry, University of Kuopio, Kuopio, Finland and Metkinen Chemistry, Kuopio, Finland.
authors.forename: Andrey
authors.initials: A
authors.lastname: Yagodkin
authors.forename: Alex
authors.initials: A
authors.lastname: Azhayev
authors.forename: Jarkko
authors.initials: J
authors.lastname: Roivainen
authors.forename: Maxim
authors.initials: M
authors.lastname: Antopolsky
authors.forename: Alexei
authors.initials: A
authors.lastname: Kayushin
authors.forename: Maria
authors.initials: M
authors.lastname: Korosteleva
authors.forename: Anatoly
authors.initials: A
authors.lastname: Miroshnikov
authors.forename: John
authors.initials: J
authors.lastname: Randolph
authors.forename: Hugh
authors.initials: H
authors.lastname: Mackie
mesh_terms: D002851:Chromatography, High Pressure Liquid; D008956:Models, Chemical; D015394:Molecular Structure; D009841:Oligonucleotides / Q000737:chemistry*; D009943:Organophosphorus Compounds / Q000138:chemical synthesis* / Q000737:chemistry; D021241:Spectrometry, Mass, Electrospray Ionization; D013873:Thionucleotides / Q000737:chemistry
chemical_list: D009841:Oligonucleotides; D009943:Organophosphorus Compounds; D013873:Thionucleotides; C434331:phosphoramidite