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Fluoride‐Labile Protecting Groups for the Synthesis of Base‐Sensitive Methyl‐SATE Oligonucleotide Prodrugs
Author(s) -
GuerlavaisDagland Typhaine,
Meyer Albert,
Imbach JeanLouis,
Morvan François
Publication year - 2003
Publication title -
european journal of organic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.825
H-Index - 155
eISSN - 1099-0690
pISSN - 1434-193X
DOI - 10.1002/ejoc.200300069
Subject(s) - chemistry , phosphoramidate , prodrug , phosphoramidite , nucleobase , oligonucleotide synthesis , trimethylsilyl , oligonucleotide , protecting group , fluoride , combinatorial chemistry , moiety , phosphate , stereochemistry , organic chemistry , medicinal chemistry , dna , biochemistry , inorganic chemistry , alkyl
Base‐sensitive methyl‐SATE oligonucleotide prodrugs (prooligos) were synthesized using fluoride‐labile protection groups on the nucleobases and on certain internucleosidic phosphate linkages. The combination of [( tert ‐butyl)(diphenyl)silyloxymethyl]benzoyl (SiOMB) and (trimethylsilyl)ethyl (TSE) groups is well adapted for synthesis of these compounds using phosphoramidite chemistry on a solid support. The prooligo was anchored on the support via a phosphoramidate linkage. A final treatment with Et 3 N·3HF in THF efficiently releases the prooligo from the solid support and cleaves the SiOMB and TSE groups. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003)