293300-96-6Relevant articles and documents
Synthesis of 4-Thiouridine, 6-Thioinosine, and 6-Thioguanosine 3′,5′-O-Bisphosphates as Donor Molecules for RNA Ligation and Their Application to the Synthesis of Photoactivatable TMG-Capped U1 snRNA Fragments
Kadokura, Michinori,Wada, Takeshi,Seio, Kohji,Sekine, Mitsuo
, p. 5104 - 5113 (2007/10/03)
4-Thiouridine, 6-thioguanosine, and 6-thioinosine 3′,5′-bisphosphates (9, 20, and 28) were synthesized in good yields by considerably improved methods. In the former two compounds, uridine and 2-N-phenylacetylguanosine were converted via transient O-trimethylsilylation to the corresponding 4- and 6-O-benzenesulfonyl intermediates (2 and 13), which, in turn, were allowed to react with 2-cyanoethanethiol in the presence of N-methylpyrrolidine to give 4-thiouridine (3) and 2-N-phenylacetyl-6-thioguanosine derivatives (14), respectively. In situ dimethoxytritylation of these thionucleoside derivatives gave the 5′-masked products 4 and 15 in high overall yields from 1 and 11. 6-S-(2-Cyanoethyl)-5′-O-(4,4′-dimethoxytrityl)-6-thioinosine (23) was synthesized via substitution of the 5′-O-tritylated 6-chloropurine riboside derivative 22 with 2-cyanoethanethiol. These S-(2-cyanoethyl)thionucleosides were converted to the 2′-O-(tert-butyldimethylsilyl)ribonucleoside 3′-phosphoramidite derivatives 7, 18, and 26 or 3′,5′-bisphosphate derivatives 8, 19, and 27. Treatment of 8, 19, and 27 with DBU gave thionucleoside 3′,5′-bisphosphate derivatives 9, 20, and 28, which were found to be substrates of T4 RNA ligase. These thionucleoside 3′,5′-bisphosphates were examined as donors for ligation with m32,2,7 G5′ pppAmUmA, i.e., the 5′-terminal tetranucleotide fragment of U1 snRNA. The 4-thiouridine 3′,5′-bisphosphate derivative 9 was found to serve as the most active substrate of T4 RNA ligase with a reaction efficiency of 96%.
