86872-09-5Relevant articles and documents
Direct One-Pot Synthesis of Nucleosides from Unprotected or 5-O-Monoprotected d -Ribose
Downey, A. Michael,Richter, Celin,Pohl, Radek,Mahrwald, Rainer,Hocek, Michal
supporting information, p. 4604 - 4607 (2015/09/28)
New, improved methods to access nucleosides are of general interest not only to organic chemists but to the greater scientific community as a whole due their key implications in life and disease. Current synthetic methods involve multistep procedures employing protected sugars in the glycosylation of nucleobases. Using modified Mitsunobu conditions, we report on the first direct glycosylation of purine and pyrimidine nucleobases with unprotected d-ribose to provide β-pyranosyl nucleosides and a one-pot strategy to yield β-furanosides from the heterocycle and 5-O-monoprotected d-ribose.
New stereocontrolled synthesis of isomeric C-branched-β-D-nucleosides by intramolecular free-radical cyclization- opening reactions based on temporary silicon connection
Xi, Zhen,Agback, Peter,Plavec, Janez,Sandstroem, Anders,Chattopadhyaya, Jyoti
, p. 349 - 370 (2007/10/02)
Silicon-bearing allyl group tethered to a 2′ or 3′-hydroxyl group onto the radical generated at the vicinal 2′ or 3′ center in the free-radical precursors 11, 15, 19 and 23 were used to promote intramolecular stereocontrolled free-radical-cyclization to give 12a + 12b, 16, 20 and 24 in 60-70% yields. The configuration at the 2′ or the 3′ center of the allylsiloxane group dictated the stereochemical outcome of the radical cyclization reaction to give cisfused seven-membered rings in compounds 16, 20 and 24 (from 15, 19 and 23, respectively) due to relatively long Si-O bond and large C-Si-O bond angle leading to exclusive 7-endo cyclization. The only exception to this was found in the radical-cyclization of 11 in which both cis-fused and trans-fused seven-membered rings 12a and 12b were formed as inseparable mixture almost in equal amounts. The seven-membered siloxane ring in the radical-cyclized products 12a + 12b, 16, 20 and 24 were then opened up by a simple oxidation reaction to give different 1,5-diols 13a + 13b, 17, 21 and 25 in high yields. The 5′-O-(4-methoxytrityl) group from 13a + 13b, 17, 21 and 25 was then removed to give pure and isomeric C-branched nucleosides 14a, 14b, 18, 22 and 26, respectively. The acid catalyzed isomerization of the pentofuranose ring in 17 to a pyranose system in 18 has been concluded on the basis of comparative structural analysis of 17 and 18 by 500 MHz1H-NMR spectroscopy. The configurations of triol 18 are C-2′(S), C-4′(R), C-5(R), C-6(S), C-7(S) which are also the configurations of the corresponding chiral centers in the precursors 16 and 17. Note that the acid catalyzed isomerization of furanose in 17 to pyranose ring in 18 has been achieved with full retention of anomeric configuration. The configuration of C-3′ in compounds 14a. 14b, 22, and C-2′ in 26 has been elucidated by 1D differential nOe experiments by 1H-NMR spectroscopy at 500 MHz in D2O solution at 293K. The estimation of the 3JHH coupling constants led us to calculate dihedral angles of 14a, 14b, 17, 18, 22 and 26 using the Karplus-Altona algorithm which have allowed us to define the conformational parameters of their constituent sugar moieties. Molecular mechanics calculations have been subsequently performed on the initial NMR structures of 17 and 18 to give their energy minimized conformations. The structures of 18 has been finally confirmed by estimating proton-proton distances derived from their nOe build-up rates by 2D NOESY experiments at 293K at different mixing times.
