Avecia Limited

King's College London

Efamol Holdings Plc

Colin Bernard Reese

Quanlai Song

A process for the synthesis of a phosphorothioate triester is provided. The process comprises the coupling of an H-phosphonate with an alcohol in the presence of a solution comprising both a coupling agent and a sulfur transfer agent. Preferably, the H-phosphonate and alcohol are protected nucleosides or oligonucleotides.

Process for the preparation of phosphorothioate triesters

A process for the synthesis in solution phase of a phosphorothioate triester is provided. The process comprises the solution phase coupling of an H-phosphonate with an alcohol in the presence of a coupling agent to form an H-phosphonate diester. The H-phosphonate diester is oxidised in situ with a sulfur transfer agent to produce the phosphorothioate triester. Preferably, the H-phosphonate and alcohol are protected nucleosides or oligonucleotides. Oligonucleotide H-phosphonates which can be used in the formation of phosphorothioate triesters are also provided.

Solution phase synthesis of oligonucleotides

A process for the preparation of a compound of formula (1):is provided, which comprises the reaction a compound of formula (2):with a compound of formula Al(OR)under substantially anhydrous conditions. X, and Xare each independently H or a protecting group, B is a base; R is an alkyl, alkoxyalkyl, alkenyl or alkynyl group, each of which may be optionally substituted, and L is a leaving group.

2'-Substituted RNA preparation

A process for the synthesis in solution phase of a phosphorothioate triester is provided. The process comprises the solution phase coupling of an H-phosphonate with an alcohol in the presence of a coupling agent to form an H-phosphonate diester. The H-phosphonate diester is oxidized in situ with a sulfur transfer agent to produce the phosphorothioate triester. Preferably, the H-phosphonate and alcohol are protected nucleosides or oligonucleotides. Oligonucleotide H-phosphonates which can be used in the formation of phosphorothioate triesters are also provided.

Inter alia, a process for the production of a nucleoside phosphorothioate derivative corresponding to the following general formula (I): ##STR1## characterized in that it comprises reacting a salt of a nucleoside H-phosphonate corresponding to the following general formula (II): ##STR2## with a thiol transfer agent corresponding to the following general formula (III):

Nucleoside phosphorothioate derivatives, synthesis and use thereof

Hydroxyl projecting groups for organic synthesis

A process for protecting the 2'-hydroxyl of a nucleoside, which can then be used in the chemical synthesis of polyribonucleotides, comprising the reacting of a protected nucleoside of formula I ##STR1## wherein B is a nucleoside heterocyclic base and R' is a hydroxyl-protecting group, with 1-N-aryl-4-alkoxy-1,2,5,6-tetrahydropiperidine of formula II ##STR2## wherein Ar is an aryl group possessing an electron-withdrawing substituent which renders said protecting group acid labile and R is C.sub.1 -C.sub.4 alkyl, in the presence of an acid catalyst and a solvent to yield the compound of formula II below: ##STR3##

Protection of hydroxy function with 1-N-aryl-4-alkoxy-piperidin-4-yl

A process for the production of a 5-substituted derivative of a 2,3'-anhydro-2'-deoxyuridine preferably corresponding to the following general formula: ##STR1## wherein R.sup.1 represents H, alkyl, aryl, halogeno or CF.sub.3 ; characterized in that it comprises heating a 5-substituted derivative of a 2'-deoxyuridine preferably corresponding to the following general formula: ##STR2## wherein R.sup.1 is as defined above; in the presence of a sulphite transfer reagent and preferably a solvent is disclosed. This process improves the production of valuable intermediates and hence facilitates and reduces the cost of production of pharmacologically-interesting compounds.

Growing community of inventors

London, United Kingdom

Colin Bernard Reese