Carbanucleosides

In addition to terpenes (as described above), carbohydrates have also been used as substrates in domino metathesis reactions, the aim being to synthesize enan-tiopure polyhydroxylated carbocyclic rings. These structures are components of several biologically active compounds such as aminoglycoside antibiotics [254], inositol phosphates [255], and carbanucleosides [256]. An efficient entry to this skeleton was developed by Madsen s group using a domino RCM/CM of the carbohy-... 

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 method used for the preparation of carbanucleosides was based on the RCM cyclization of simple sugar derivatives as shown in Fig. 21.34... 

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. 

S. Sahabuddin, A. Roy, M. G. B. Drew, B. G. Roy, B. Achari, and S. B. Mandal, Sequential ringclosing metathesis and nitrone cycloaddition on glucose-derived substrates A divergent approach to analogues of spiroannulated carbanucleosides and conformationally locked nucleosides, J. Org. Chem., 71 (2006) 5980-5992. 

Palladium(0)-catalyzed allylation of nucleophiles (the Tsuji-Trost reaction) is a versatile synthetic method that has gained immense popularity in recent years. Rarely applied to ambident nucleophilic aromatic heterocycles before 1991, the Tsuji-Trost reaction has been extensively used in the chemistry of these compounds since 1991. Two factors have played decisive roles in this increased interest in the Pd(0)-catalyzed allylation of such heterocyclic rings one is that, unlike other alkylation procedures, the Pd(0)-catalyzed allylation can sometimes give the product of thermodynamic control when applied to ambident nucleophiles and the second is that the Tsuji-Trost allylation has become one of the standard methods for synthesizing carbanucleosides, which are important antiviral compounds (93MI1, 93MI2). Of course, the double bond of an allylic system can be modified in different directions, thus adding versatility to the Tsuji-Trost reaction. 

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. 

The review is organized by size of the ring and, within the size, by the nature and number of the heteroatom(s) contained in the ring. Fused heterocycles, as purine bases, are treated separately. Recently, Pd(0)-catalyzed allylation of purine bases and structurally related heterocycles has become one of the standard methods for preparing carbanucleosides having, in many cases, real antiviral activity. This is, of course, a subject of great interest. 

Table VII summarizes additional examples of allylations of 190 and 191 as well as of cytosine 200 and 5-methylcytosine 201 (Scheme 44) with electrophiles 74, rac-166, and rac-204 together with the targeted final products. Reactions with glycoside 74 and with vinyl epoxide 204 always occur with overall retention of configuration. The reactions with cyclopentene derivatives are related to the preparation of synthetic carbanucleosides with antiviral action.

A very similar elaboration of the levo isomer (-)-263 (Scheme 54) has been reported by Theil, von Janta-Lipinski, and co-workers (94TL1961 95T761). Thus, the reaction of (-)-263 with 6-chloropurine 270 under Pd(0) catalysis gave 271, featuring the unusual stereochemistry characteristic of this type of carbanucleoside then 271 was converted into the homo-... 

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]. 

Baumgartner, J. et al. Chemo-enzymatic Approaches to Enantiopure Carbasugars and Carbanucleosides. 1998 [86]... 

The enantioselective syntheses of carbanucleosides (e.g., 80) have also been reported where the key step is the enantioselective allylic amination of 78 with a nucleobase (here 79) (Eq. 7) [168]. A chiral phosphine bearing a carboxyl group has also been shown to be effective for this class of substrate [169]. 

The oxazoline AT-oxides have been converted into cyano alcohols or hydroxy esters which were known precursors to carbanucleosides such as carbovir, aris-teromycin, and valienamine which is a glycosidase inhibitor. 

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