Wolfgang Pieken

Novel nucleosides via intramolecular functionalization of 2,2′-anhydrouridine derivatives

Abstract The generation of novel ribonucleoside analogues derived from 2,2′-anhydrouridines by a 3′-hydroxyl directed intramolecular nucleophilic substitution of the 2′-position is described. The methodology allows for the efficient, regio- and stereoselective elaboration of the 2′-position, often under exceptionally mild reaction conditions.

An improved synthesis of 2′-azido-2′-deoxyuridine

Abstract A high yield process for the conversion of 2,2′-cyclouridine to 2′-azido-2′-deoxyuridine was developed. The procedure utilizes a lithium azide:TMEDA complex generated in situ from the reaction of lithium fluoride and azidotrimethylsilane in DMF with TMEDA added as a co-solvent.

2′-Deoxy-2′-alkoxylaminouridines: Novel 2′-substituted uridines prepared by intramolecular nucleophilic ring opening of 2,2′-O-anhydrouridines

Abstract Natural and unnatural modified nucleosides and nucleotides play important roles in biology, medicine, and as biomedical research tools. Reported herein is an application of synthetic methodology developed for the stereo- and regiospecific introduction of structural modifications at the 2′-position of uridine nucleosides. A novel class of modified nucleosides, 2′-alkoxylamino-2′-deoxy uridines, are prepared by intramolecular nucleophilic addition of a 3′-tethered alkoxycarbamate nucleophile to the 2′-position with concomitant opening of a 2,2′-anhydrouridine.

Efficient Synthesis of 2′-Amino-2′-deoxypyrimidine 5′-Triphosphates

Abstract The synthesis of 2′-amino-2′-deoxypyrimidine 5′-triphosphates is described. The 2′-amino-2′-deoxyuridine 5′-triphosphate is obtained from uridine in four steps with 25% overall yield. The 2′-amino-2′-deoxycytidine 5′-triphosphate is obtained from uridine in seven steps with 13% overall yield.

Tc-99m-Labeling of Modified RNA

The synthesis of Tc-99m-labeled, modified RNA is reported. This new class of radiopharmaceuticals is of potential interest as target specific imaging agents. The preparation of N3S-RNA was achieved by coupling protected MAG2-units to amino modified ONs. The N3S-RNA was Tc-99m-labeled with 90-95% radiochemical yield and specific activities of 37MBq/nmol leading to 1:1-Tc-99m-N3S-aptamers.

Synthesis of Tc-99m-labeled, modified RNA

Abstract The synthesis of Tc-99m-labeled, modified RNA is reported. This new class of radiopharmaceuticals is of potential interest as target specific imaging agents. The preparation of N 3 S-conjugated RNA was achieved by coupling S-protected MAG 2 -units to amino modified RNA in solution or on solid support. The starting S-protected MAG 2 building blocks ( 1 R-S-CH 2 -CO-Gly-Gly- 2 R: 1 R = Ac, t Bu-S; 2 R = OH, OSu) were obtained by a simple 4- or 5-step synthesis. The MAG 2 -amide-RNA-conjugates were successfully Tc-99m-labeled with high yield and specific activities of 37MBq/nmol leading to 1:1-Tc-99m-N 3 S-aptamers.