Nucleoside und nucleotide. Teil 4. Festphasensynthese von Oligonucleotiden an einem unlöslichen, makroporösen Träger

Insoluble, macroreticular, highly cross‐linked polystyrene with projecting mono‐methoxytrityl chloride groups 4 was prepared and condensed with thymidine (T D ) as well as with 1‐(2′‐deoxy‐ß‐D‐ribofuranosyl)‐2(1 H )‐pyridone ( II d ) to give the polymers 5 and 6 respectively, containing approximately 465 μmoles resp. 650 μmoles of bound nucleoside per gram of polymer. A standard procedure for removal of the products from the support is described. Condensation of the polymer‐bound nucleosides 5 and 6 , respectively, with 3′‐O‐acetyl‐thymidine‐5′‐phosphate ( 7 ) in the presence of mesitylenesulfonyl chloride (MS) and subsequent removal from the polymer yielded the dinucleoside phosphates T d ‐T d ( 9 ) and II d ‐T d ( 11 ) respectively. Condensation of the polymer 8 with 3′‐O‐acetyl‐thymidine‐5′‐phosphate ( 7 ) in the presence of MS and cleavage of the polymer linkage gave the trithymidine diphosphate (T d ‐T d ‐T d ) ( 13 ). Phosphorylation of the polymer‐bound nucleosides 5 and 6 with ß‐cyanoethyl phosphate in presence of MS took place in 3′‐position. Similarly the polymer‐bound dinucleoside phosphates 8 and 10 gave 16 and 17 respectively.