Oligonucleosides with a Nucleobase‐Including Backbone. Part 11

A linear and a convergent synthesis of uridine‐derived backbone‐base‐dedifferentiated (backbone including) oligonucleotide analogues were compared. The Sonogashira cross‐coupling of the alkyne 1 and the iodide 2 gave the dimer 4 that was C ‐desilylated and again coupled with 2 to give the trimer 6 ( Scheme 1 ). Repeating this linear sequence led to the pentamer 10 . Coupling yields were satisfactory up to formation of the trimer 6 , but decreased for the coupling to higher oligomers. Similarly, coupling of the alkynes 5, 7 , and 9 with the iodouridine 3 gave, in decreasing yields, the trimer 12 , tetramer 13 , and pentamer 14 , respectively. The dimeric iodouracil 20 was synthesized by coupling the alkyne 17 with the iodide 16 to the dimer 18 , followed by iodination at C(6/I) to 19 and O ‐silylation ( Scheme 2 ). The iodinated dimer 23 was prepared by iodinating and O ‐silylating the known dimer 21 . Coupling of 20 and 23 with the dimer 5 , trimer 7 , and tetramer 9 gave the tetramers 8 and 13 , the pentamers 10 and 14 , and the hexamer 15 , respectively ( Scheme 3 ). The oligomers up to the pentamer 14 were deprotected to provide the trimer 24 , tetramer 25 , and pentamer 26 ( Scheme 4 ). There was no evidence for the heteropairing of the pentamer 26 and rA 7 , nor for the pairing of rU 5 and rA 7 , while a UV melting experiment showed the beginning of a sigmoid curve for the interaction of rU 7 with rA 7 . Therefore, the pentamer 26 does not pair more strongly with rA 7 than rU 5 .