Synthesis of 5′-C-Branched Thymidines and Conversion to Phosphoramidites

A cyclic dinucleotide with a four-carbon 5′-C-to-5′-C connection; synthesis by RCM, NMR-examination and incorporation into secondary nucleic acid structures

“…21,31,38, 40 Wang and Middleton determined the configurations of 3 and 4 by the conversion to the two 3 ,5 -O-di(t-butyl)silyl derivatives and subsequent NOEdifference spectroscopy. 32 However, direct comparison of our NMR-data of 3 and 4 with the reported data 32 was not reliable due to intense spectral overlap. Finally, the 5 (S)-configuration of 5 was confirmed, indirectly, by converting 5 to 3.…”

“…Thus, a Grignard reaction with 1 using allylMgCl and CuCN has afforded both 5 -epimers 3 and 4 as a 1 : 1 mixture in 63% yield. 31,32 On the other hand, a stereoselective procedure starting with 2 applying allyltrimethylsilane and BF 3 :OEt 2 afforded exclusively the 5 (S)-configurated 5 -O-TMS-protected analogue of 5 in an impressive 95% yield after silylation. 33 We decided to repeat and evolve these procedures and to confirm the configuration of the products.…”

Synthesis and modelling of DNA junction and minor groove zipper motifs incorporating the double-headed nucleoside 5′(S)–C-(thymine-1-ylmethyl)thymidine

“…NMR spectra were recorded on a 300 MHz Varian spectrometer. The values for d are in ppm relative to tetramethylsilane as internal standard for the 1 H-NMR assignments, relative to the solvent signal (DMSO-d 6 39.52; CDCl 3 77.16) for the 13 C-NMR assignments, and relative to 85% H 3 PO 4 as external standard for the 31 P-NMR spectra. Assignments of NMR spectra are based on ( 1 H, 1 H)-COSY, ( 1 H, 13 C)-hetcor and/or DEPT spectra following nucleoside naming style, i.e.…”

“…Thus, several examples of introducing additional carbons and functionalisation on the 5 -C position have been shown in the literature. [11][12][13][14][15][16][17] From standard protocols, the 3 -protected derivative 4 was obtained and converted by oxidation and a Wittig olefination to the known 5 -deoxy-5 -methylene derivative 5 (Scheme 1). 11, 12 The stereoselective epoxidation of this alkene has been described by Wang and Middleton, 12 and we used this preparation of the epimeric mixture of epoxides (S : R ∼ 9 : 1), and a subsequent treatment with thymine and potassium carbonate in hot DMF to give the (S)-configured protected double-headed nucleoside 6 in 39% yield.…”