Glycosyl fluorides glycosylations

The glycosyl fluoride glycosylation promoted by BF3-OEt2 is applied in the key step of the total synthesis of ipopolysaccharide (LPS) derivative [102] and D-myo-inositol monomannoside [103], Also, glycosylation of 4 -OH of 66 with... 

In typical procedures for glycosyl fluoride glycosylation reactions, the glycosyl fluoride is mixed with an aglycon alcohol and a Lewis acid promoter. As noted above, Mukaiyama s original disclosure described the use of a combination of tin(II) chloride and silver perchlorate as the activator [20], but since then, many other... 

Halide derivatives may be fluorides, chlorides, or bromides. Fluorides are best prepared by the reaction of hydroxy groups with (diethylamino)sulfur trilluoride ( DAST M. Sharma, 1977) or of glycosyl thioethers with DAST/NBS (K.C. Nicolaou, 1990 B). The other halides are usually only introduced at the glycosidic position, where treatment with hydrogen chloride... 

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). 

Purine, 6-bromo-9-/3-D-(2,3,5-tri-0-acetyl)ribofuranosyl-synthesis, 5, 598 Purine, 6-carboxy-reactions, 5, 549 Purine, 8-carboxy-reactions, 5, 549 Purine, 2-chloro-reactions, 5, 561 synthesis, 5, 597 Purine, 6-chloro-alkylation, 5, 529 glycosylation, 5, 529 oxidation, 5, 539 3-oxides reactions, 5, 554 synthesis, 5, 595 reactions, 5, 561, 595 with ammonia, 5, 562 with fluorides, 5, 563 with trimethylamine, 5, 562 9- -D-ribofuranoside synthesis, 5, 560 synthesis, 5, 597, 598 Purine, 8-chloro-amination, 5, 542 Purine, 6-chloro-8-ethoxy-synthesis, 5, 591 Purine, 6-chloro-9-ethyl-dipole moment, 5, 522 Purine, 6-chloro-2-fluoro-riboside... 

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. 

Because of the high C - F bond energy, glycosyl fluorides are stable in comparison to the other glycosyl halides, and this character has attracted much attention. They have been prepared in many different ways. One of them, rather classical, is through addition of the elements of HF (for example, HF in benzene ), BrF, or IF to per-O-acylated glycals. ... 

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)... 

Noyori and coworkers found that tetrafluorosilane or trimethylsilyl tri-flate catalyzes the condensation of appropriately protected glycopyranosyl fluorides with trimethylsilyl ethers or alcohols. The strong affinity of silicon for fluorine was considered to be the driving force for this reaction. In the case of Sip4, attack of a nucleophile on the glycosyl cation-SiFj ion-pair intermediate was anticipated. Thus, condensation of 2,3,4,6-tetra-O-benzyl-a- and - -D-glucopyranosyl fluorides (47a and 47fi) with methyl... 

Glycosylation utilizing glycosyl fluorides in the presence of BF3 OEt2 was reported concurrently by Ishido, Voznij, Nicolaou, and their respective coworkers, and Kunz and Sagar. Ishido and coworkers prepared 1 — 1 a,a and y ,/ )-disaccharides under BFj catalysis by condensation of... 

Glycosides may also be prepared by enzyme-catalyzed condensation reactions utilizing a glycosyl fluoride. Thus 6-0-a-maltosylcyclodextrins were prepared enzymically from a-maltosyl fluoride (obtained from the corresponding heptaacetate by Zemplen deacetylation) and cyclodex-trins. " ... 

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... 

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