C-Aryl glycoside

A combination of Cp nCX —A CXC) (where = cyclopentadienyl) effectively promotes the Friedel-Crafts coupling of glycosyl fluorides with aromatic compounds, such as trimethoxyben2ene or methoxynaphthalenes. The derived C-aryl glycosides are potent antitumor agents (39). 

Stereoselective inverse-demand hetero (4 + 2) cycloadditions. A Chiral Template for C-Aryl Glycoside Synthesis. Chiral allenamides2 4 had been used in highly stereoselective inverse-demand hetero (4 + 2) cycloaddition reactions with heterodienes.5 These reactions lead to stereoselective synthesis of highly functionalized pyranyl heterocycles. Further elaboration of these cycloadducts provides a unique entry to C-aryl-glycosides and pyranyl structures that are common in other natural products (Scheme 1). 

This methodology has been applied to carbohydrate derivatives and provides a route to certain C-aryl glycosides. 

Scheme 6.12 Rearrangement to C-aryl glycosides from aryl O-glycosides following a-selective synthesis using glycosyl phosphates.

C-Aryl-glycosides are wide-spread in Nature (34., 35). The biological importance led to various synthetic... 

Spirocyclic C-aryl glycosides are central structural skeletons of papulacandins that constitute a family of novel antifungal antibiotics isolated from a strain of Papularia sphaerosperna. They have shown potent in vitro antifungal activity against Candida albicans, Candida tropicalis, Pneumocystis carinii, among other microorganisms [110],... 

C. Jaramillo and S. Knapp, Synthesis of C-aryl glycosides, Synthesis p. 1 (1994). M. H. D. Postema, Recent developments in the synthesis of C-glycosides, Tetrahedron 48 8545 (1992). 

In the synthesis of C-aryl glycosides, one must consider the following two issues pertaining to selectivity ... 

Friedel-Crafts coupling of an aromatic compound with an activated glycosyl donor is a classic, standard method for C-aryl glycoside synthesis [1,2]. Early interests were primarily centered at C-nucleoside synthesis, so that data were accumulated for the ribofuranosyl series with degradable aromatics to construct the nucleic base (Scheme 2) [5]. Equation (1)... 

As a result of recent progress in 0-glycoside synthesis, a variety of new glycosyl donors and their specific activation methods are now available, some of which have also been applied to C-aryl glycoside synthesis. Table 1 shows some examples for the coupling... 

The most useful feature of this reaction is that the C-aryl glycoside bond forms regioselec-tively at the position ortho to the phenolic hydroxyl. As shown in Scheme 7, the ortho-... 

T. Matsumoto, M. Katsuki, and K. Suzuki, Cp2ZrCl2-AgC104 Efficient promoter in the Friedel-Crafts approach to C-aryl glycosides. Tetrahedron Lett. 30 833 (1989). 

C. Jaramillo and S. Knapp, Synthesis of C-aryl glycosides, Synthesis, (1994) 1-20. 

C-Aryl glycosides.2 This combination (1 2) also activates glycosyl fluoride for C-glycosidation. The glycosidation was used to obtain the anthracene P-C-olivosides 2 and 3 of vineomycin B2. 

Hydrogenolysis of the racemic isoxazolyl alcohol 955 followed by an acid-mediated cyclization of the resulting diketone provides the dihydropyran-4-one 956, an intermediate during a synthesis of C-aryl glycosides (Equation 373) <20020L977>. 

Furthermore, coupling to form C-aryl glucals, as precursors to C-aryl glycosides, was carried out both from the C-metallated glucal154 and onto the C-iodo glucal (equations 90 and 91)155. A synthesis of vineomycinone B2 methyl ester has resulted from this chemistry. A vinyl-vinyl coupling reaction has also formed the cornerstone of aryl steroid synthesis (equation 92)156. 

The Classical and Umpolung Strategies in C-Aryl Glycoside Construction... 

C-aryl glycoside formation, 88 biological functions, 87 8,10-di-O-methylbergenin synthesis, 87-89... 

Regioselective synthesis of unsymmetrical C-aryl glycosides using silicon tethers, as disposable linkers, has been developed (Scheme 55). Deprotonation of 304 with Bu Li led to the formation of an intermediate benzyne 305 that underwent cycloaddition to deliver 306. When 306 was treated with TBAF in DMF at 70°C, the tether was cleaved and 307 was obtained in 80% yield. The acid-catalyzed opening of the oxabicycloheptadiene ring afforded the glycosyl naphthols 308 in quantitative yield <2003JA12994>. 

Ramesh, N.G. and Balasubramanian, K.K. 1992. Reaction of 2,3-unsaturated aryl glycosides with Lewis acids A convenient entry to C-aryl glycosides. Tetrahedron letters, 33 3061-64. 

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