2-Deoxyribose as a Rich Source of Chiral 5-Carbon Building Blocks

Abstract

We have developed concise routes to a number of useful chiral 5-carbon synthetic building blocks using readily available O-1-methyl-2-deoxyribose as starting material. Novel transformations include the use of indium triflate to catalyze the oxidation of a methyl furanoside to the corresponding lactone with MCPBA and the Vasella-type fragmentation of a 5-iodo furanoside using chromium(II) chloride when zinc proved ineffective. In addition, 3,4-disubstituted piperidine derivatives were prepared without hydroxyl group protection via a simple reductive amination reaction.

Protecting-Group-Free Synthesis of 2-Deoxy-Aza-Sugars

“…Installation of an iodide at the primary position was then attempted by refluxing a solution of methyl 2-deoxy- D -ribose 12 , triphenylphosphine, I 2 and imidazole in THF for 2 hr. Unfortunately, these conditions led to significant degradation, however milder reaction conditions, involving stirring the same reagents at room temperature for 18 hr [ 19 ], allowed for the preparation of methyl 2,5-dideoxy-5-iodo- D -riboside ( 10 ) in satisfactory yield (73%).…”

A greener enantioselective synthesis of the antiviral agent North-methanocarbathymidine (N-MCT) from 2-deoxy-d-ribose

“…The recent publication by Michel and Strazewski on the improved synthesis of chiral cyclopentenone 3b 18 and the utilization of natural 2-deoxy- d -ribose as rich chiral pool,19 prompted us to investigate the possibility of preparing the bicyclic hexanol precursor 4 from this inexpensive building block. The retrosynthetic analysis for this novel route (Figure 2) resembles in great part Jeong's initial approach towards chiral cyclopentenone 3b 13.…”

Efficient preparation of 2-nitroimidazole nucleosides as precursors for hypoxia PET tracers

“…Although the mixture of methyl glycosides α - and β - 10 [18] was tosylated [19] at −25 °C for 3 days in 59% yield ( α / β  = 1.2/1), some ditosylate 16 was formed as well (11%, α / β  = 1.4/1). Analytical samples of the anomers for characterization could not be obtained by column flash chromatography.…”

“…As envisioned, the yields with the benzoyl protecting group were higher than with the acetyl version. The anomeric configuration of α - and β - 19 ( 1 H NMR; α -1-H′: d, J  = 6.6 Hz; β -1-H′: dd, J  = 7.5 and 5.6 Hz) was assigned in analogy to nucleosides α - and β - 14 ( 1 H NMR; α -1-H′: dd, J  = 6.3, 0.8 Hz; β -1-H′: dd, J  = 6.6, 6.1 Hz) and the literature known analogue [19] of β - 14 with two 4-toluoyl protecting groups ( 1 H NMR; β -1-H′: t, J  = 6.5 Hz) instead of the acetyl and benzoyl group. The 1-H′ hydrogen atoms of the α -anomers resonate as doublets or as doublets of doublets with one coupling constant being very small.…”