Synthesis of C-nucleosides

Hydrogenation was accomplished over freshly prepared W-2 Ra-Ni in a 5 1 methanol-water mixture containing 3 equiv of acetic or boric acid. The hydrogenolysis has been applied smoothly to the synthesis of C-nucleosides... 

Synthesis of C-Nucleosides in which the Glycosylic Carbon Atom is Attached to Two Carbon Atoms... 

This Section is concerned with the synthesis of C-nucleosides having the Type A arrangement of atoms attached to the glycosylic carbon atom, and covers the synthesis of pseudouridine (1), show-... 

Diazopyrazoles and imidazoles are useful intermediates in the synthesis of pyrazolo- and imidazolo-tetrazinones, which have shown anticancer activity, especially the mitozolomide that had curative activity against L1210 and P388 leukemia (84JMC1% 87JMC357). 4-Diazopyrazole are used in the synthesis of C-nucleoside antibiotics such as pyrazolomycin [81JCS(P1)2374]. 

The use of chiral azomethine imines in asymmetric 1,3-dipolar cycloadditions with alkenes is limited. In the first example of this reaction, chiral azomethine imines were applied for the stereoselective synthesis of C-nucleosides (100-102). Recent work by Hus son and co-workers (103) showed the application of the chiral template 66 for the formation of a new enantiopure azomethine imine (Scheme 12.23). This template is very similar to the azomethine ylide precursor 52 described in Scheme 12.19. In the presence of benzaldehyde at elevated temperature, the azomethine imine 67 is formed. 1,3-Dipole 67 was subjected to reactions with a series of electron-deficient alkenes and alkynes and the reactions proceeded in several cases with very high selectivities. Most interestingly, it was also demonstrated that the azomethine imine underwent reaction with the electronically neutral 1-octene as shown in Scheme 12.23. Although a long reaction time was required, compound 68 was obtained as the only detectable regio- and diastereomer in 50% yield. This pioneering work demonstrates that there are several opportunities for the development of new highly selective reactions of azomethine imines (103). 

In a convenient experimental procedure, nitrogen heterocycles 3 are alkylated by a mixture of a carboxylic acid 4 and [bis(trifluoroacetoxy)iodo]benzene in boiling benzene or under irradiation in dichloromethane at room temperature (Scheme 2) [11, 12]. A similar procedure has been used for the stereoselective synthesis of C-nucleosides and their analogs via photolysis of the gulonic acid derivatives, (diacetoxy)iodobenzene, and the appropriate heteroaromatic bases [13]. 

The use of the hypervalent iodine reagent [bis(trifluoroacetoxy)iodo]benzene has been reported to be effective in the synthesis of C-nucleoside-like compounds. Radical decarboxylation of a suitably protected uronic acid, initiated photochem-ically, followed by addition of a heterocyclic base provided the C-nucleoside in high yield.154 The mode of action involves initial radical formation of 122 (Scheme 33), followed by introduction of the base and radical coupling.155 The anomeric selectivity was high in some examples, and low in others—lepidine gave the highest proportion of the ( anomer. Isolated yields were poor to moderate. 

Togo and Yokoyama developed a general and efficient method for the synthesis of C-nucleosides employing radical coupling pathways.53 -b Several of these C-nucleosides have been synthesized by ionic pathways but they require many steps and suffer a lack of generality. The thiohydroxamates derived from pentose or 2-tetrahydrofuryl carboxylic acid, Scheme 31, gave the corresponding C-nucleoside derivatives 77 in the presence of an appropriate heteroaromatic compound.53b... 

C-Nucleosides. The first step in a new synthesis of C-nucleosides involves reaction of ethoxycarbonylethylidenetriphenylphosphoranc with the 2,3-di-O-isopropylidene-D-ri-bose derivative 1 to give the acyclic product 2. On treatment with C6H5SeCl, 2 gives a single cyclic ribose derivative (3), shown to be the 3-anomer by the conversion shown here to a derivative (6) of showdomycin. In addition, several other 1 p-substituted 1-deoxyribose derivatives were prepared. 

A Heck-type coupling of 2,3-dihydrofuran with a secondary chloroacetamide produced the two double bond isomers in about 2 1 ratio <03TL5751>. A palladium-catalyzed Heck-type coupling between the heterocyclic iodide shown below and 2,3-dihydrofuran was used as Ae key step in the synthesis of C-nucleosides. Conditions were optimized to include AgjCOj to prevent double migration and thereby obtain a good yield of the desired 2,5-dihydrofuran products <03JMC1449>. 

The tandem Wittig-conjugate-addition reaction shown below has found widespread application for the synthesis of C-nucleosides from aldoses, in most cases ribose (see also Section 4.7.1.2.2. for the related reaction of aldoses with nitroalkanes). 

Poonian, M S, Nowoswiat, E F, A novel precursor for the synthesis of C-nucleoside analogs. Synthesis of the C-nucleoside analogs of ribavirin, bredinin, and related compounds, J. Org. Chem., 45, 203-208, 1980. 

Palladium-catalyzed arylation and vinylation of alkene is referred to as the Mizoroki-Heck reaction and is one of the most widely used Pd(0)-catalyzed C-C bond formations in organic synthesis. However, the reaction has not been extensively employed for C-glycosylation [96]. The example shown in O Scheme 67 outlines the reaction of iodopyridine and furanose gly-cal for the synthesis of C-nucleoside [97]. The mechanism began with the oxidative addition of iodopyridine to Pd(0) catalyst, and the resulting organo-palladium species was inserted by... 

Synthesis.—By Cycloaddition. The Noyori cycloaddition of halogeno-ketones to furans is now sufficiently well established to provide a firm base for the successful synthesis of C-nucleosides. For example, the ketone (109) has been prepared ... 

An alternative method for the synthesis of C-nucleosides is the formation of a new C-C bond between the sugar and heterocycle moieties. Palladium-mediated coupling reaction of furanoid glycals 182 [221] (Fig. 32) with (1,3-dimethyl-2,4-dioxo-l,3-dihydropyrimidin-5-yl) mercuric acetate gave moderate... 

The synthesis and resolution of the bicyclic lactone (66)(actually obtained from a non-carbohydrate precursor) has been described, and its use in the synthesis of C-nucleosides was also extensively... 

There has been a surge of interest in the synthesis of C-nucleosides, doubtless inspired by the antimetabolite and antibiotic properties of several representatives. 

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