Glycosylation with glycosyl fluorides

Jona, H, Takeuchi, K, Mukiyama, T, 1,2-cis Selective glycosylation with glycosyl fluoride by using a catalytic amount of trifluoromethanesulfonic acid (TfOH) in the coexistence of molecular sieve 5 A (MSS A), Chem. Lett, 1278-1279, 2000. 

Yanagisawa, M, Mukaiyama, T, Catalytic and stereoselective glycosylation with glycosyl fluoride using active carbocationic species paired with tetrakis(pentafluorophenyl)borate or trifluorometha-nesulfonate, Chem. Lett., 224-225, 2001. 

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). 

Now with the two requisite coupling partners available, the next step is the elaboration of the AE ring system (see Scheme 11). Through the application of previously developed conditions for activation of glycosyl fluorides,24 the convergent union of compounds 19 and 20 can be achieved, giving a 4.5 1 mixture of axial and equatorial isomers in favor of the desired axial glycoside 60 (ca. 70 % yield). 

In the Koenigs-Knorr method and in the Helferich or Zemplen modifications thereof, a glycosyl halide (bromide or chloride iodides can be produced in situ by the addition of tetraalkylammonium iodide) is allowed to react with a hydrox-ylic compound in the presence of a heavy-metal promoter such as silver oxide, carbonate, perchlorate, or mercuric bromide and/or oxide,19-21 or by silver triflu-oromethanesulfonate22 (AgOTf). Related to this is the use of glycosyl fluoride donors,23 which normally are prepared from thioglycosides.24... 

For the purposes of this chapter, an arbitrary distinction is made between protonic and thermal activation, wherein protonic activation is caused by the action of acid at room temperature or lower, and thermal activation refers to the use of elevated temperatures with or without the addition of acid. In fact, in both cases, the initial steps in the postulated mechanisms are protonation of the C-2 oxygen atom followed by elimination of the aglycone to yield a ketohexofuranosyl or pyranosyl cation, which is the reactive intermediate in certain circumstances, this might be in equilibrium with the derived glycosyl fluoride. 

Glycosyl fluorides may be prepared by displacement of per-O-acyl or suitably protected 2-0-acyl 1-halides (Cl or Br) with fluoride [AgF (Refs. 28 and 29), KHF2 (Ref 30) or AgBF4 (Ref 31)]. -o-Glucopyranosyl [ F]fluo-... 

Glycosyl fluorides have also been prepared by treatment of per-O-acyl or partially 0-acylated sugars with hydrogen fluoride [liquid HF (for example, see Refs. 38 and 39) or HF in acetic acid or dichloromethane], as exemplified by 2,3,4-tri-O-benzyl-a-D-xylopyranosyl (18), a-D-glucopyranosyl (19), tetra-O-pivaloyl-a-D-glucopyranosyl (20), and 2,3,5-tri-O-acetyl-D-xylofur-anosyl fluorides (21) (see Table 1). Frequently, HF treatment - leads to... 

The preparation of glycosyl fluorides is described next. Aiming to have a convenient glycosyl donor convertible into 1,2-CM-furanosides, Mukaiyama and coworkers prepared 2,3,5-tri-O-benzyl-yS-D-ribofuranosyl fluoride (36y3) by treatment of a protected D-ribofuranose (35) with 2-fluoro-1 -meth-ylpyridinium tosylate (FMPTs) the total yield was raised by anomerizing the simultaneously produced a-1-fluoride (36a, 7, p 66, 72.f 24 Hz) to 36 (7, F 63.5 Hz, 72,F very small ) by treatment with BF3-OEt2. 

Glycosylations utilizing the aforedescribed glycosyl fluorides are described next. In 1981, Mukaiyama and coworkers attempted to prepare 1,2-cw-glycosides by utilizing the relatively stable (as compared with other glycosyl halides) 2,3,4,6-tetra-0-benzyl-)8-D-glucopyranosyl fluoride (47)5)... 

C-Glycosyl derivatives may be prepared by utilizing glycosyl fluorides. Ishido and coworkers reported that the reaction of 2,3,5-tri-O-benzyl-a-(36a) or - -D-ribofuranosyl fluoride (36fi) with isopropenyl trimethylsilyl ether under BF3 catalysis (0.1 -0.05 mol. equiv. for the fluoride, in ether or acetonitrile) gave a mixture of 4,7-anhydro-5,6,8-tri-C)-benzyl-l,3-dideoxy-D-altro- (139, major) and -D-a//o-2-octulose (140) 139 was stated to isomerized to 140 (should be vice versa) under Lewis acid catalysis. Similar... 

Other inverting glucosidases which conform to the pattern of direct hydrolysis of glycosyl fluorides having the correct anomeric configuration, and transglycosylation with inversion if the anomeric configuration is opposite to that of the natural substrates are trehalase from rabbit renal cortex and from the yeast Candida tropicalis, and ) -D-xylosidase from Bacillus pu-milis. ... 

Specific glycosidases. Based on their reactivity with the respective 2-deoxy-2-fluoro-o - and -y -D-glycosyl fluorides, the enzymes were found to fall into three groups. 

Evidence for a glycosyl-enzyme intermediate of finite lifetime with inverting a-D-glycosidases, and details of its reaction, came from studies with 2,6-anhydro-l-deoxyhept-l-enitols and glycosyl fluorides. - Analysis of hydration and hydrolysis products on the one hand, and of glycosyla-tion products on the other, indicated an intermediate that could be approached by water from the yff-face only of the ring, and by other glycosyl acceptors only from the a-face (see Schemes 4 and 5 This can be considered a proof of the principle of microscopic reversibility of chemical reactions. 

Scheme 8.3. Glycoside formation from glycosyl fluorides with a metallocene activator.

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