Towards the synthesis of inosine building blocks for the preparation of oligonucleotides with hydrophobic alkyl chains between the nucleotide units.
The scientific objective of the research reported in this manuscript was the synthesis of novel phosphoramidite building blocks for the preparation of lipophilic oligonucleotides. Reaction of inosine (4) with 4-oxopentyl-4-methylbenzoate (2c) in the presence of triethyl orthoformate and 4M HCl in 1,4-dioxane gave a diastereoisomeric mixture of the ketals 5. Subsequent 4,4'-dimethoxytritylation at the 5'-hydroxyl afforded (R)-6 + (S)-6 which could be separated chromatographically. Detoluoylation gave compounds (R)-7 and (S)-7. Phosphitylation of a diastereoisomeric mixture of 7 led to a mixture of four diastereoisomers of the corresponding 2-cyanoethylphosphoramidites 8.
Köstler
Karl
K
Organische Materialchemie und Bioorganische Chemie, Institut für Chemie, Fachbereich Biologie/Chemie, Universität Osnabrück, Osnabrück, Germany.
Rosemeyer
Helmut
H
D000577:Amides / Q000737:chemistry*; D006851:Hydrochloric Acid / Q000737:chemistry; D007288:Inosine / Q000138:chemical synthesis* / Q000737:chemistry*; D008956:Models, Chemical; D015394:Molecular Structure; D009841:Oligonucleotides / Q000138:chemical synthesis* / Q000737:chemistry*; D009943:Organophosphorus Compounds / Q000138:chemical synthesis* / Q000737:chemistry*; D010756:Phosphoric Acids / Q000737:chemistry*; D013237:Stereoisomerism
D000577:Amides; D009841:Oligonucleotides; D009943:Organophosphorus Compounds; D010756:Phosphoric Acids; D007288:Inosine; C011067:phosphoramidic acid; D006851:Hydrochloric Acid