Studies on the Stereoselective Synthesis of Deuterated D‐Ribose Derivatives

Abstract

In view of the importance of the site-specific substitution of the H-atom by its stable isotope 2 H in a stereoselective/stereospecific manner at the pentose sugar residue, decreasing the spectral overcrowding in various regions of 1D and 2D homo-and heteronuclear correlation spectra of oligo-DNA and -RNA, there is always a need for the development of new methods for the incorporation of 2 H at different sites of a ribose. High-yielding multistep syntheses of C(2)-, and (5R)-and (5S)-3,5-deuterated ribose derivatives have been envisaged for the application of site-specific incorporation of multilabeled nucleosides into oligomers to facilitate their structure elucidation by NMR spectroscopy. All syntheses started from d-glucose after proper derivatization. In the case of C(2), > 97 atom-% isotope was incorporated, employing an inversion of the configuration at C(2) as the key reaction. For C(5), two different routes were envisaged: on the one hand, deuterated achiral reagent was treated with a conformationally locked sugar moiety 15, while, on the other, chiral protonated sources were used to transfer the H-atom to a C(5)-deuterated aldehyde 18. In all cases, enantiomeric and isotopic purities were found to be as high as > 97% as determined by NMR spectroscopy.

Mechanistic Studies on Pyridoxal Phosphate Synthase: The Reaction Pathway Leading to a Chromophoric Intermediate

“…The 5 S -diastereotopically enriched alcohol 9 was prepared in several steps from the commercially available allofuranose 6 . Straightforward hydrogenolysis followed by acetonide removal resulted in ribose 4 .…”

“…Synthesis of ( 5 S ) - [ 5- 2 H 1 ] - and ( 5 R ) - [ 5- 2 H 1 ] -Ribose. The ribose diastereomers 4 and 5 were prepared from the known alcohol 9 using a modified procedure. , All solvents were reagent grade and distilled over CaH 2 when noted as dry. Proton and carbon NMR were recorded on a Bruker ARX-300.…”

Stereoselective Nucleoside Deuteration for NMR Studies of DNA

“…4 Although the first approach allows the usage of more general reducing agents, it is usually more laborious requiring many synthetic steps that frequently have insufficient stereospecificity. Therefore, a number of approaches have been used for the reduction of deuterated 5′-oxosugar derivatives by chiral hydride donors, including (−)-isobornyloxymagnesium bromide, 4 chloro(diisopinocampheyl)borane, 5 or AlpineBorane. 6 Alternatively, non-deuterated 5′-oxosugars were reduced with deuterated isobornyloxymagnesium bromide or deutero-AlpineBorane, 7 with the latter approach successfully utilized for preparation of 5′-deuterated ribonucleosides.…”

Rules and Stereoelectronic Guidelines for the Anionic Nucleophilic Displacement of Furanoside and Furanose O-Sulfonates

“…( b ) (i) β­(1,2,4)-α(3)-O2-triflates normally undergo anionic S N 2 displacement successfully (eq ) due to the beneficial workings of the Vicinal Triflate Effect and limited opposing steric hindrance. …”