Olefin Metathesis Route to Antiviral Nucleosides

Abstract

The success of the early nucleoside agents, the toxicity and metabolic instability of many nucleoside analogues and the effects of viral pathogens on public health are driving the design, synthesis and evaluation of new nucleoside analogues. In this context, a powerful reaction has emerged over the past decade that has fundamentally changed the outlook on nucleoside chemistry: the olefin metathesis reaction. This review is designed to give an overview of the synthesis of some nucleosides of biological interest, according to their structural types (e.g., neplanocins and aristeromycin analogues, 2',3'-unsaturated nucleoside analogues, and acyclonucleosides), using metathesis reactions by employing either the alkoxy imido molybdenum catalyst developed by Schrock and various ruthenium carbene catalysts developed by Grubbs, Hoveyda-Grubbs and Nolan.

A Materials Approach to Site‐Isolation of Grubbs Catalysts from Incompatible Solvents and m‐Chloroperoxybenzoic Acid

“…chemistry would make their combination in cascade reactions a useful discovery. [70][71][72][73][74][75][76][77] In addition, evidence in the literature suggested that the Grubbs catalyst and MCPBA were incompatible. [78][79][80][81][82][83][84][85][86] In related work by others, it was shown that ruthenium compounds readily react with MCPBA to generate ruthenium oxo species.…”

Simple Methodology for Heck Arylation at C‐8 of Adenine Nucleosides

“…The combination (o-tol) 3 P (L1)/PdA C H T U N G T R E N N U N G (OAc) 2 /Et 3 N (2:1 ligand/Pd stoichiometry) proved to be effective and was superior in reactivity to the well-defined Cat1. The role of additional L1 is currently unclear but the one example in Table 2 where equimolar amounts (10 mol% each) of L1 and PdA C H T U N G T R E N N U N G (OAc) 2 were used (entry 23) demonstrates that the additional equivalent of L1 is necessary, the absence of which led to retardation of the reaction. Scheme 2.…”

“…[16] Table 2 is a listing of the most relevant results from this series of experiments. With iodobenzene, formation of the catalytic species from L1/PdA C H T U N G T R E N N U N G (OAc) 2 in situ proved to be superior to the use of Cat1 (entries 1 and 2 in Table 2). Although 31 P{ 1 H} NMR experiments have not provided insight into the observed differences in reactivity, it may be possible that the additional equivalent of L1 is not simply a bystander (see below).…”

“…The result of this reaction was essentially identical to that obtained with Cat1 alone (entry 8). On the other hand, the additional equivalent of L1 seems necessary when used in combination with PdA C H T U N G T R E N N U N G (OAc) 2 . For example, as seen from entry 23, equimolar amounts of L1 and PdA C H T U N G T R E N N U N G (OAc) 2 (10 mol% each) led to a substantially slower reaction compared to entry 22 where 20 mol% of L1 and 10 mol% of PdA C H T U N G T R E N N U N G (OAc) 2 were employed.…”

“…[1,2] In this context, palladium-mediated transformations play a prominent role in providing access to hitherto unknown structural motifs. [3] In addition, reactivities of complex molecules such as nucleosides may not necessarily parallel those of simpler compounds and they can often provide novel insights.…”