Synthesis of carbanucleoside

The key transformation in the synthesis of carbanucleosides, reported by Horvath, was based on the Ferrier-II rearrangement and led to the important derivative ara-cyclohexenyl-A (Fig. 19).32... 

Another version operating under neutral conditions (Scheme 3) uses vinyl epoxides (7) as the source of the i73-allylpalladium complex 8. Here, the alkoxide is generated by opening of the epoxide simultaneously with the formation of the cationic complex. The final compound (9) possesses an alcohol functional group. This variant is very important in the synthesis of carbanucleosides. 

A number of reviews have been published highlighting advancements in the synthesis of carbanucleosides using ring-closing metathesis. As such, only some of the more recent and synthetically challenging syntheses of these compounds are reported here. 

A new route to racemic ds-4-amino-2-cyclopentene-l-methanol as a key intermediate in the synthesis of carbanucleosides has been described. An attempt to resolve the amino alcohol by way of its 10-camphorsulfonate failed. 

The photoinduced-addition of alcohols to cycloalkenones has been investigated by Fraser-Reid and co-workers,4 by Paquette,5 and was used as the key step in the synthesis of the prostaglandin endoperoxide analogue (15S)-hydroxy-9a,11a-epoxymethanoprosta-(52,13E)-dienoic acid,6 and for the recent synthesis of 2, 3 -dideoxy-3 -hydroxymethyl-5 -carbanucleosides.7 No work (other than our own) has been reported on the photoinduced-addition of alcohols to 5-substituted furan-2(5H)-ones. 

Apart from a short communication [18] where carbafuranose mercapto derivatives were prepared to be used as intermediates in the formal synthesis of certain carbanucleosides, only one report has been published dealing with the synthesis of thiocarbafuranoses [7c]. 

The preparation of the carbanucleoside aristeromycin and carbacyclic precursors of neplanocin A are mentioned in Chapter 19. The preparation of intermediates for the synthesis of unsaturated carbocyclic nucleosides is covered in Chapter 20. 

Pd(0)-catalyzed allylation of purine derivatives with cyclopentenol esters and other alicydic allylic esters is a key step in the preparation of natural and unnatural carbanucleosides with antiviral activity. Carbanucleosides cannot be hydrolyzed as conventional nucleosides are since the anomeric carbon atom is absent therefore, their activity and stability render carbanucleosides valuable compounds. Although much work has been performed with aUylic acetates, a few examples of the application of allylic carbonates in carbanucleoside synthesis have been reported and their number will increase in the future. Two earlier examples by Trost and co-workers are in Scheme 30, including the numbering system of the purine skeleton. Other examples refer to more couplings of purines with flve-membered or with six-membered... 

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