Mats Thelin

Nucleoside H-phosphonates. X: Studies on nucleoside hydrogenphosphonothioate diester synthesis

Abstract Synthesis and chemical properties of nucleoside H-phosphonothioates are discussed in the context of possible application of these compounds as intermediates in the synthesis of oligonucleotide analogues.

Nucleoside H-Phosphonates. XI. A Convenient Method for the Preparation of Nucleoside H-Phosphonates

Abstract A simple synthetic method for the preparation of nucleoside 3′-H-phosphonates, consisting of reaction of suitably protected nucleosides with phosphonic acid in the presence of a condensing agent, has been developed.

Nucleoside Phosphonates. Development of Synthetic Methods and Reagents

Abstract In this paper a short account of our recent research concerning development of new synthetic methods and new reagents for the preparation of DNA and RNA fragments and their analogues is given. #Dedicated to Professor Yoshihisa Mizuno on the occasion of his 75th birthday. ¶Present address: Astra Production Chemicals, S-151 85 Sodertalje, Sweden.

3-H-2,1-benzoxathiol-3-one 1-oxide - a new reagent for stereospecific oxidation of nucleoside H-phosphonothioate diesters

Abstract Oxidation of diastereomerically pure nucleoside H-phosphonothioate diesters with 3- H -2,1-benzoxathiol-3-one 1-oxide ( 1 ) was found to be stereospecific and occurred with retention of configuration. Absolute configurations of diribonucleoside H-phosphonothioate diastereomers were established via stereochemical correlation using m-chloroperoxybenzoic acid for stereospecific conversion of ribonucleoside H-phosphonothioate to the corresponding H-phosphonate diesters.

3H-1,2-benzothiaselenol-3-one. A new selenizing reagent for nucleoside H-phosphonate and H-phosphonothioate diesters

A new selenium-transferring reagent, 3H-1,2-benzothiaselenol-3-one (1), has been developed for the conversion of nucleoside H-phosphonate and nucleoside H-phosphonothioate diesters into the corresponding seleno analogues. The reagent is soluble in common organic solvents and shows an enhanced rate of selenium transfer compared to elemental selenium or potassium selenocyanate. Selenization with the reagent 1 is stereospecific and most likely occurs with retention of configuration at the phosphorus centre.

Some Chemical and Stereochemical Aspects of Ribonucleoside H-Phosphonate and H-Phosphonothioate Diester Synthesis

Abstract Some chemical and stereochemical aspects of condensation of ribonucleoside 3′-H-phosphonates, 3′-H-phosphonomonothioates and 3′4%-phosphonodithioates into the corresponding diesters 4 and 5 together with oxidation and sulfurization of the latter ones, are discussed.

Studies on the activation pathway of phosphonic acid using acyl chlorides as activators

The activation pathway of phosphonic acid with acyl chlorides has been investigated with the aim of evaluating the synthetic utility of the intermediates involved for the preparation of hydrogen-phosphonate (H-phosphonate) monoesters. It is found that, depending on the amount of condensing reagent used, three distinctive intermediates are potentially formed, namely the pyrophosphonate (2), the phosphono-acyl mixed anhydride (3a), and the triacyl phosphite (4a). Their chemical reactivities towards oxygen nucleophiles indicate that the most suitable intermediate for H-phosphonate monoester synthesis is the pyrophosphonate (2).

Evaluation of the Use of the t-Butyldimethylsilyl Group for 2′-Protection in RNA-Synthesis Via the H-Phosphonate Approach

Abstract Two model compounds. 1 and 2. have been studied to test the stability of the tbutyldimethylsilyl group towards anhydrous acid, aqueous ammonia and tetrabutylammonlum fluoride In THF. Results of relevance to cleavage and migration of phosphodiesters during deprotection of synthetic RNA will be presented.

On the Sulfurization of H-Phosphonate Diesters and Phosphite Triesters Using Elemental Sulfur

Sulfurization of tetracoordinate and tricoordinate P(III) derivatives, namely, H-phosphonate diesters, H-phosphonothioate diesters, and phosphite triesters with elemental sulfur under various experimental conditions, was investigated.

RNA-Synthesis Using the H-Phosphonate Approach and an Improved Protecting Group Strategy

Abstract An improved version of the H-phosphonate approach to RNA-synthesis is presented and the studies that led to alterations in the protecting group strategy are discussed.