Fluoro sugars 3- deoxy-3-, synthesis

The 5-deoxy-fluoro-sugar derivatives (15) and (16) have been synthesised from D-glucose for incorporation into potential chemotherapeutic nucleosides. Improvements to Ogawa s method for the synthesis of 2-deoxy- -glycosides, involving addition of arylsulphenyl esters of the desired aglycon to glycals, with... 

Syntheses of 3-deoxy-3-fluoro sugars are described next. A rapid synthesis aimed at 3-deoxy-3-[ F]fluoro-D-glucose ( F-3DFG) was developed. ... 

In 1969, Adamson, Foster, and others - reported the synthesis of 2-deoxy-2-fluoro sugars by addition ofCFjOF (in CFCI3, — 80°) to 3,4,6-tri-O-acetyl-l,5-anhydro-2-deoxy-D-flra/)/>zo-hex-l-enitol (61 3,4,6-tri-O-acetyl-D-glucal). The reagent fluorinates 61 electrophilically - °° at C-2, to afford c/v-addition products trifluoromethyl 3,4,6-tri-C)-acetyl-2-deoxy-2-... 

Aldolases accept a wide range of aldehydes in place of their natural substrates and permit the synthesis of carbohydrates such as azasugars, deoxy sugars, deoxythio sugars, fluoro-sugars, and C8 or C9 sugars. In the case of D-fructose-1,6-diphosphate aldolase (FDP aldolase, Type A), more than 75 aldehydes have been identified as substrates [143]. 

Dihydroxylation of 19 with OSO4/NMO occurred without discrimination between the alkene faces to afford the fluoro sugars ( )-20 and ( )-21 as a 1 1 mixture of separable cis and trans isomers. Synthesis of the 4,4-difluoro-4-deoxy-13-DL-ribo-pyranside derivatives ( )-23e-f and 4,4-difluoro-4-deoxy-13-DL-lyxo-pyranside derivatives ( )-24e-f were realized via transacetalisation of the difluoro homoallylic alcohols 17e-f followed by RCM and dihydroxylation, respectively. 

One year later, Kitazume et al. also described the synthesis of 6-deoxy-6,6,6-trifluoro-D-mannose and D-allose using intermediate (45,55)-76 (Scheme 5.10). Thus, oxidation of 76 with potassium permanganate in the presence of catalytic 18-crown-6 provided the diol 84 as the only isomer in 42% yield. Protection of diol moiety in 84 as its acetonide followed by DlBAL-H reduction afforded the lactol 85, which was subjected to the t-BuOK promoted isomerization to give the desired fluoro sugar 86 in 35% yield. The precursor 87 of fluoro sugar 89 was obtained by reduction... 

Enzymic synthesis of several hexose derivatives from dihydroxy-propanone and glyoeraldehgde derivatives included a preparation of 6-deoxy-6-fluoro-sugars. All four deoxyfluoro-oc-D-glucopyranosyl phosphates have been synthesized and their acid-catalyzed hydrolysis... 

Several enzymatic procedures have been developed for the synthesis of carbohydrates from acyclic precursors. Aldolases appear to be useful catalysts for the construction of sugars through asymmeteric C-C bond formation. 2-deoxy-KDO, 2-deoxy-2-fluoro-KDO, 9-0-acetyl sialic acid and several unusual sugars were prepared by a combined chemical and enzymatic approach. Alcohol dehydrogenases and lipases have been used in the preparation of chiral furans, hydroxyaldehydes, and glycerol acetonide which are useful as building blocks in carbohydrate synthesis. 

N-Acetvlneuraminic Acid Aldolase. A new procedure has also been developed for the synthesis of 9-0-acetyl-N-acetylneuraminic acid using the aldolase catalyzed reaction methodology. This compound is an unusual sialic acid found in a number of tumor cells and influenza virus C glycoproteins (4 ). The aldol acceptor, 6-0-acetyl-D-mannosamine was prepared in 70% isolated yield from isopropenyl acetate and N-acetyl-D-mannosamine catalyzed by protease N from Bacillus subtilis (from Amano). The 6-0-acetyl hexose was previously prepared by a complicated chemical procedure (42.) The target molecule was obtained in 90% yield via the condensation of the 6-0-acetyl sugar and pyruvate catalyzed by NANA aldolase (Figure 6). With similar procedures applied to KDO, 2-deoxy-NANA and 2-deoxy-2-fluoro-NANA were prepared from NANA. 

I. D. Blackburne, P. M. Fredericks, and R. D. Guthrie, Studies on unsaturated sugars with particular reference to the synthesis of 6-deoxy-6-fluoro derivatives, Aust. J. Chem., 29 (1976) 381-391. 

Korytnyk and coworkers have shown that reactions of xenon difluoride with acetylated glycals in the presence of boron trifluoride are a convenient route for the synthesis of 1,2-difluoro sugars, while the addition of fluorine to the double bond occurred predominantly from the less hindered side and cis adducts were mainly formed75, 76. Stereoselective transformation of tri-O-acetyl-D-galactal with xenon difluoride at -20 to +5 °C, without a catalyst in CFC13, after hydrolysis, afforded 2-deoxy-2-fluoro-D-galactose in 63% yield77. 

Fu and Bobek reported in 1978 the synthesis of 2 -deoxy-5-fluoro-4 -thiouridine (127) and its a anomer, the first 2 -dco y-4 -tliioribonuclcosidcs to be prepared. In 1991 the groups of Walker,Secrist, 2 and Ucniclii -- simultaneously reported the syntheses of 2 -deoxy-4 -thioribopyrimidine nucleosides starting from 2-deoxy-D-eryz/zz-o-pentose, L-arabinose, and a non-sugar precursor, respectively. All of these preparations involved the intermediacy of a convenient... 

Of the halogenated 1,6-anhydrohexopyranoses, the main interest has been directed to the iodo derivatives384,630-632 as intermediates for the synthesis of deoxy sugars, and to the fluoro derivatives (for a review, see Ref. 773), interesting from both the chemical and the biochemical point of view. The chloro and bromo derivatives have been examined only rarely.94,168,319,437... 

The first preparation of a secondary deoxyfluoro sugar, other than by total synthesis, involved the cleavage of 2,2 -anhydro-3-( 8-D-arabino-furanosyl) uracil (3) to give 3-(2-deoxy-2-fluoro-/3-D-ribosyl) uracil. This reaction, which can be extended to cleavage by hydrogen bromide or chloride, is at pr ent the only route to 2-deoxy-2-fluoro-D-ribose deriva-... 

Sucrose synthetase. The fructose derivatives 1-azido-l-deoxy-, 1-fluoro-l-deoxy-, 6-deoxy-, 6-fluoro-6-deoxy-, and 4-fluoro-4-deoxy-fructose have been used as glycosyl acceptors in the sucrose synthetase-catalyzed synthesis of sucrose analogs12031. 6-Deoxy- and 6-fluoro-6-deoxy-fructose were generated in situ from the corresponding glucose derivatives under catalysis by glucose isomerase[2031. Sucrose synthetase has also been extensively employed in the synthesis of nucleotide sugars[2041. 

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