Fructose 4-deoxy-, 4-fluoro

Deoxy-4-fluoro-D-fructose (552) was prepared (59%) by fermentation of 3-deoxy-3-fluoro-D-mannitol with Gluconobacter oxydans. The structure of 552 (fi-T) form) was confirmed by the n.m.r. spectrum, which resembles that of 4-deoxy-4-fluoro-Q -D-sorbopyranose (553) 552 was identical with one of the products obtained from the oxirane-ring opening of 3,4-anhy-dro-l,2-0-isopropylidene- -D-tagatopyranose with KHFj. 

Several fluoro analogs of ketoses have been reported 1,6-dideoxy-1,6-difluoro-D-fructose was readily obtained from 2,3-O-isopropyli-dene-l,6-di-0-p-tolylsulfonyl-)3-D-fructofuranose by treatment with potassium fluoride in 1,2-ethanediol under a stream of carbon dioxide.96 Surprisingly, although the 6-sulfonyloxy group would be expected to be more reactive than the 1-sulfonyloxy group,97-99 no selectivity was observed. The failure to obtain 1-deoxy-l-fluoro-D-fructopyranose96 from 2,3 4,5-di-0-isopropylidene-l-0-(methylsulfonyl) (or p-nitro-phenylsulfonyl)-/3-D-fructopyranose or phenyl 3,4,5-tri-O-acetyl-l-O-(methylsulfonyl)-/3-D-fructopyranoside by treatment with potassium or sodium fluoride in 1,2-ethanediol, N,N-dimethylformamide, or form-amide at elevated temperatures may be attributed to the fact that nu-... 

Deoxy-4-fluoro-D-glucose 4-deoxy-4-fluoro-D-fructose 1,6-bisphophate 1 30 HK11 5000 PCI" FK" 2000 71... 

Stoichiometric quantities of uridine diphosphate glucose were used, in the presence of a transfer enzyme, sucrose synthetase, in the soluble state (extraction given). Coupling with modified D-fructose gave sucroses modified on the D-fructosyl group, on the 1 -3-mmol scale. Thus were prepared l -deoxy-l -fluoro- (59%),98 4 -deoxy-4 -fluoro- (16%), and l -azido-l -deoxy-sucrose (15%).71 6-Deoxy-6-fluoro-D-glucose was isomerized to 6-deoxy-6-fluoro-D-fructose with isomerase, and gave 6 -deoxy-6 -fluoro-sucrose.71... 

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. 

Xylose isomerase converts a wide range of D-glucose as well as L-idose derivatives modified at position 5 into the corresponding ketose. 5-Deoxy-5-fluoro-D-xylulose and a variety of 5,6-dimodified open-chain analogs of D-fructose, namely the 5,6-diazido-5,6-dideoxy, 6-azido-5,6-dideoxy, 6-azido-5,6-dideoxy-5-fluoro, 5,6-di-deoxy-5-fluoro, 5,6-dideoxy-6-fluoro and 5,6-dideoxy-5,6-difluoro derivatives were prepared with glucose isomerase (Fig. 17-24)[234, 235. ... 

Figure 17-24. Production of 5-deoxy-5-fluoro-D-xylulose and 5,6-dimo-dified open-chain analogs of D-fructose with xylose isomerase.

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]. 

We have developed preparative enzymatic syntheses of several unusual hexoketoses using fructose-1,6-diphosphate aldolase (FDP-aldolase, E.C.4.1.2.13) as catalyst and dihydroxyacetone phosphate (DHAP) and an aldehyde as substrates (15). The enzyme appears to be very specific for DHAP but will accept a variety of aldehydes as acceptors. The ketose-1-phosphates prepared are converted to the phosphate free ketoses after removal of the phosphate group by acid- or phosphatase-catalyzed hydrolysis. The ketoses can be isomerized stereospecifically to aldoses catalyzed by glucose isomerase (E.C.5.3.1.5.) from Flavobacteriuum arborescens. The equilibrium mixtures of aldoses and ketoses are then separated by chromatography on Dowex 50 (Ba ) or Dowex 1 (HSO "). Figure 1 illustrates the preparation of a mixture of 6-deoxy-6-fluoro-D-fructose... 

A number of studies on the metabolism of 3FG and 4FG in Locusta miaratoria have been undertaken. Both 3FG and 4FG are toxic to locust with LD50 s of 4.8 mg/g and 0.6 mg/g respectively. In vitro studies showed that 3FG is metabolized in the fat body, via the NADP-linked aldose reductase, to 3-deoxy-3-fluoro-D-glucitol (3FGL). This metabolite was detected in the hemolymph of the insect and shown to be both a competitive inhibitor and a substrate for NAD-linked sorbitol dehydrogenase, thereby generating 3-deoxy-3-fluoro-D-fructose (3FF) (541. Subsequently, it was shown by in vivo radio-respirometric analysis of C02 and appropriate chase experiments, that 3FG metabolism irreversibly inhibits glycolysis and not the hexose monophosphate shunt or tricarboxylic acid cycle (55). In addition, the release of fluoride ion and H20 from D-[3- H]-3FG was also observed. Based on the mechanism of aldolase (55) and triosephosphate isomerase... 

The Specificity of Pyranose-2-oxidase and the of 4-Deoxy-4-fluoro-D-fluoro-D-fructose... 

The chemical synthesis of deoxyfluoro-D-fructoses has been restricted to 1-deoxy-l-fluoro-D-fructose ( 3) and 1,6-dideoxy-l,6-difluoro-D-fructose ( 4). The... 

Azido-sugar derivatives such as 51 were synthesized conventionally from the known trichloroethylidene carbamate derivatives such as 52, prepared by a one-pot acetalation-epimerization procedure from methyl a-D-mannopyrano-side (see Section 2.1) The 2,6-anhydro-5-azido-2-C-hydroxymethyl-L-allohep-tose derivative 53 has been synthesized from a racemic norbornenone derivative. 6-Azido-6-deoxy-, and 5,6-diazido-, 5-azido-6-fluoro- and 6-azido-5-fluoro-5,6-dideoxy-D-fructoses 54 have been prepared by polyol dehydrogenase-catalysed isomerization of the corresponding D-glucose derivatives. ... 

Enzymatic dehydrogenation of 3-deoxy-3-fluoro-D-mannitol using enzymes of Gluconobacter oxydana provides a route to i4,-deox -4.-fluoro-D-fructose, whose structure was confirmed b H, C, and F n.m.r. spectroscopy. The molecule adopts the C (D) conformation in aqueous solution. 

O -Benzoyl-1,2-0 -isopropylidene- p-D-fructopyranose, 1-62 1-0-Benzyl-3-deoxy-3-fluoro-D-fructose, D-74 l-Bromo-l-deoxy-2,3 4,5-di-0-isopropylidene-p-D-fructopyranose, B-67 Butyl p-D-fructofuranoside, F-84... 

Deoxy-3,5-di-0-toluoyl-p-D- r> /Aro-pentofuranosyl chloride, D-357 l-Deoxy-l-fluoro-2,3 4,5-di-0-isopropylidene-D-fructose, D-73... 

---