title: The application of the AMB protective group in the solid-phase synthesis of methylphosphonate DNA analogues.
abstract: Partially methylphosphonate-modified oligodeoxynucleotides were synthesized on solid-phase by employing the easily removable 2-(acetoxymethyl)benzoyl (AMB) group as base-protecting group. Although a rapid AMB deprotection can be accomplished in methanolic potassium carbonate, the lability of the methylphosphonate linkage towards potassium carbonate/methanol excludes the use of this deprotection reagent. Thus, saturated ammonia solution in methanol was investigated as an alternative reagent for AMB removal. It is demonstrated that the combination of the AMB protective group and ammonia/methanol as deprotection reagent significantly improves the synthesis of methylphosphonate-modified DNA fragments. A mild overnight treatment at room temperature is sufficient for complete removal of the AMB group, whereas deprotection of conventionally protected oligonucleotides requires much longer exposure to basic conditions at elevated temperatures.
authors.affiliation: Organon International BV, Leiden, The Netherlands.
authors.forename: W H
authors.initials: WH
authors.lastname: Kuijpers
authors.forename: E
authors.initials: E
authors.lastname: Kuyl-Yeheskiely
authors.forename: J H
authors.initials: JH
authors.lastname: van Boom
authors.forename: C A
authors.initials: CA
authors.lastname: van Boeckel
mesh_terms: D000085:Acetates; D000641:Ammonia / Q000494:pharmacology; D001483:Base Sequence; D001565:Benzoates; D002254:Carbonates / Q000494:pharmacology; D002851:Chromatography, High Pressure Liquid; D002855:Chromatography, Thin Layer; D004247:DNA / Q000138:chemical synthesis*; D009682:Magnetic Resonance Spectroscopy; D000432:Methanol / Q000494:pharmacology; D008969:Molecular Sequence Data; D015394:Molecular Structure; D009838:Oligodeoxyribonucleotides / Q000138:chemical synthesis; D009943:Organophosphorus Compounds / Q000494:pharmacology*; D011188:Potassium / Q000494:pharmacology; D016339:Spectrometry, Mass, Fast Atom Bombardment
chemical_list: D000085:Acetates; D001565:Benzoates; D002254:Carbonates; D009838:Oligodeoxyribonucleotides; D009943:Organophosphorus Compounds; C032627:methylphosphonic acid; C082521:2-(acetoxymethyl)benzoic acid; D000641:Ammonia; D004247:DNA; C037593:potassium carbonate; D011188:Potassium; D000432:Methanol