A. Van Aerschot

Synthesis of Nucleosides Fluorinated in the Sugar Moiety. The Application of Diethylaminosulfur Trifluoride to the Synthesis of Fluorinated Nucleosides

Abstract A survey is given of the different methods that have been used for the synthesis of nucleosides fluorinated in the carbohydrate moiety. In this article we describe the use of diethylaminosulfur trifluoride (DAST) as a fluorinating agent in the nucleoside field.

CYCLOHEXENE NUCLEIC ACIDS (CeNA) FORM STABLE DUPLEXES WITH RNA AND INDUCE RNASE H ACTIVITY

Cyclohexene nucleic acids (CeNA) were synthesized using classical phosporamidite chemistry. Incorporation of a cyclohexene nucleo-side in a DNA chain leads to an increase in stability of the DNA/RNA duplex. CeNA is stable against degradation in serum. A CeNA/RNA hybrid is able to activate E. Coli RNase H, resulting in cleavage of the RNA strand.

Synthesis of thymidine from 5-iodo-2′-deoxyuridine

Abstract A simple, high yield synthesis of thymidine from 5-iodo-2′-deoxyuridine is described, using tetramethyltin and tetrakis(triphenylphosphine)palladium(0) in hexamethylphosphoric triamide. Likewise, 5-phenyl- and 5-vinyl-2′-deoxyuridine can be obtained, and through reduction of the latter the 5-ethyl analogue is also at hand.

Synthesis of 2′-Deoxy-2′ -Fluoro-D-Arabinopyranopyranosyl Nucleosides and Their 3′,4′-Seco analogues

Abstract 2′-Deoxy-2′-fluoro-D-arabinopyranosyl nucleosides were synthesized by condensation of 1,3,4-tri-O-benzoyl-2-deoxy-2-fluoro-D-arabinopyranose with the appropriate silylated bases in the presence of trimethylsilyl triflate. Scission of the 3′,4′-bond by periodate oxidation followed by sodium borohydride reduction resulted in the formation of the 3′,4′-seco analogues of the 2′-deoxy-2′-fluoro-D-arabinofuranosyl nucleosides.

Homo-N-nucleosides: Incorporation into oligonucleotides and antiviral activity

Abstract Homo-N-nucleosides can be efficiently synthesized from 2-deoxyribose. When incorporated in an oligonucleotide, the compounds have a detrimental influence on duplex stability and on the catalytic activity of hammerhead ribozymes. However, homo-N-nucleosides with a guanine or adenine base moiety do exhibit selective antiviral activity against herpes simplex virus (HSV-1 and HSV-2).

Synthesis of Pyranose Nucleosides

Abstract The synthesis of pyrimidine nucleosides with a 2, 3, 4-tri-deoxy-D-glycero-hex-3-enopyranose, 2, 3, 4-trideoxy-D-glycero-hexopyranose, 2-deoxy-D-erythro-pentopyranose and 2-deoxy-2-fluoro-D-arabino-pentopyranose sugar moiety are described.

Stability measurement of oligonucleotides in serum samples using capillary electrophoresis

An in vitro stability study of unmodified and modified antisense oligonucleotides in human serum was performed with a previously developed capillary electrophoretic method using either micellar solution or entangled polymer solution depending on the oligonucleotide length to be separated. A method has been devised and validated for the extraction of oligonucleotides from serum using anion-exchange centrifugal filter units. The extracted samples were desalted by a drop dialysis method. The serum half-lives and the degradation patterns of unmodified and modified oligonucleotides are compared. The modified oligonucleotide used in this study is protected from exonuclease activity present in human serum by terminal 1,3-propanediol modification.

In Search of Acyclic Analogues as Universal Nucleosides in Degenerate Probes

Abstract Five acyclic nucleoside analogues with unnatural base moieties have been synthesized of which three successfully were incorporated into oligonucleotides. The acyclic analogue containing the base 5-nitroindazole was the least discriminating and should be further pursued for use as a universal nucleoside analogue.

Synthesis, enzymatic stability and physicochemical properties of oligonucleotides containing a N-cyanoguanidine linkage.

Abstract Nucleoside dimers with a N-cyanoguanidine linkage were synthesized and used as building blocks for oligonucleotide synthesis. Oligonucleotides composed of alternating phosphodiester and cyanoguanidine functions are still able to hybridize with a complementary natural oligodeoxynucleotide.

Dimeric building blocks with N-cyanoguanidine linkage for oligonucleotide synthesis

Abstract Synthesis of dimeric nucleoside building with a N-cyanoguanidine linkage was performed by reaction of 3′-amino-3′-deoxythymidine with S,S-dimethyl-N-cyanodithioimidocarbonate followed by reaction of the obtained isothiourea with 5′-amino-2′,5′-dideoxynucleosides. These dimers were protected in the 5′-position and converted into their phosphoramidites. Oligonucleotides were synthesized using these building blocks.