Wolfgang K.-D. Brill

Synthesis and characterization of dinucleoside phosphorodithioates

Abstract Dinucleoside phosphoramidites, H 2 S, and tetrazole react to form dinucleoside H-phosphonothioates. Oxidation with sulfur yields phosphorodithioates. Iodine oxidation in the presence of amines, alcohols, or water yields phosphorothioamidates, thiotriesters or thiodiesters.

Synthesis of dinucleoside phosphorodithioates via thioamidites

Abstract Deoxynucleosides and S-(4-chlorobenzyl)-phosphorothiodiamidites react via phosphorothioamidites to form thiophosphite triesters. Sulfur oxidation yields dinucleoside phosphorodithioate triesters which can be used to selectively introduce dithioate linkages into DNA.

Synthesis of oligonucleotide phosphorodithioates

Abstract The synthesis of DNA containing sulfur at the two nonbonding internucleotide valencies is reported. Several different routes using either tervalent or pentavalent mononucleotide synthons are described.

Oxidative and nonoxidative formation of internucleotide linkages

Abstract Activation of nucleoside 3′-hydrogenphosphonodithioates with iodine in the presence of nucleosides and amines yields dinucleoside phosphorodithioates and nucleoside phosphorodithioamidates, respectively. Similar activation of nucleoside 3′-methylphosphonothioates yields dinucleoside methylphosphonothioates.

Synthesis and p-diastereomeric resolution of nucleoside 3′-O(s-alkyl) and nucleoside 3′-O(s-aryl) methylphosphonothioates

Abstract Successive displacement of oxybenzotriazoyl moieties from methylphosphonicbisoxybenzotriazolide by a deoxynucleoside and a mercaptan yields the O,S-dialkyl and O-alkyl-S-arylmethylphosphonothioate diastereomers which can be resolved by flash column chromatography.

Synthesis of nucleoside methylphosphonothioates

Abstract Deoxydinucleotide methylphosphonothioates containing 5′-5′ and 3′-5′ internucleotide linkages were synthesized regioselectively from nucleosides and methylphosphonothioic dichloride by successive displacement of chlorine atoms. The diastereomers were resolved by hplc.

Phosphoramidites as Synthons for Polynucleotide Synthesis

Abstract Methods for the rapid synthesis of DNA and RNA are described. The procedures involve using nucleoside phosphoramidites as synthons and silica as a polymeric support. Additionally, a novel reaction involving nucleoside O-alkyl methylphosphonothioates is described.