Fluorinated disaccharides

Fluorinated 2-isoxazolines have been obtained stereoselectively from 2-(polyfluoroacyl)cycloalkanones and hydro-xylamine in the presence of catalytic BF3-OEt2 <2002HCA1960>. Enones 507 derived from disaccharides melibial and gentobial reacted with 2 equiv of hydroxylamine to afford isoxazolines 508 as an inseparable epimeric mixture in 80-83% yield. By treatment with -toluenesulfonic acid, compounds 508 underwent dehydration to give isoxazole derivatives 509 in high yields (Scheme 117) <2004T6453>. 

The base-catalyzed addition of alcohols to nitriles to give imidates proceeds well, if there are electron-attracting groups in the a-position. In such cases the Pinner synthesis is less effective, because nitrile basicity is less. TTiis shows that both methods are complementary. Recently attention has been paid to the long-known addition of alcohols to trichloroacetonitrile, since it was found that imidates prepared from protected saccharides, amino alcohols etc. and trichloroacetonitrile are useful reagents for the synthesis of nucleosides, disaccharides and other natural products. The trichloroacetimidic acid esters (240 equation 131) of fluorinated, unsaturated aliphatic alcohols °° and benzyl alcohol have been prepared for synthetic purposes. 

Disaccharide anthracyclines were synthesized, in which the daunosaraine moiety is separated from the aglycone by either a rhamnose or fucose residue. Fluorine was reported on the fucose moiety (70) [89] and on the aglycone at C-8 (71) [20] (Fig. 11). Both examples indicate two important considerations first, anthracyclines, with an activity comparable to that of DOXO, possess the daunosamine moiety not directly linked to the aglycone second, the fluorine does not lower the activity of these compounds but allows the synthesis of new derivatives with a particularly high activity in inhibiting the growth of cultured human tumor cells. 

Derivatives of MEN10755, an anthracycline analogue currently under evaluation in Phase II clinical trials [90-93], with fluorine on C-8, were synthesized (Scheme 20) and the cytotoxic and antitumor properties of disaccharide 8-fluoro-anthracyclines were markedly affected by the stereochemistry of the... 

A single acyl group has been introduced into P-cyclodextrin, either at a 2- or a 3-position, by exposure to benzoyl- or a- or P-naphthoyl chloride in alkaline aqueous acetonitrile. A Lipid A disaccharide esterified with (5)-3-hydroxytetra-decanoic acid and a Lipid A monosaccharide carrying a fluorinated JV-acyl group are referred to in Chapters 3 and 9, respectively. 

Selectfluor 93 adds first to a glycal such as 10 predominantly from above the plane of the molecule to give a syn adduct, which is susceptible to a slow anomerization and is further displaced by the alcohol 59 heating improves yields and also affects anomeric configuration. A major 2 -deoxy-2 -fluoro-a-D-man o disaccharide 94 is thus produced (Scheme 22). A judicious choice of protective groups was shown to improve the stereoselectivity of both fluorination and nucleophilic addition. 

And 4 -deoxyfluoro derivatives of lactose and their ceramide glycosides have been produced using (trimethylsilyl)ethyl glycosides as intermediates. Some other fluorinated analogues of disaccharides are referred to above. Disaccharides based on olivomycosides have been produced, the key step being as indicated in Scheme 16, the iodine atom being deemed to have participated in the reaction. 

Riess and co-workers [252-263] have prepared nonionic fluorinated surfactants with a polyhydroxy hydrophile by perfluoroalkylating natural products such as monosaccharides and disaccharides, pentitols, hexitols, and so forth. Per-6>-acetylglycopyranosyl bromides were reacted with 1 l-(F-alkyl)-10-undecenols,... 

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