N.F. Taylor

Flourocarbohydrates : Part XVIII. 9-(3-deoxy-3-flouro-β-D-xylofuranosyl)adenine and 9-(3-deoxy-3-flouro-α-D-arabinofuranosyl)adenine

An alternative synthesis of 3-deoxy-3-fluoro-α-D-xylose (4a) from methyl 2,3-anhydro-5-O-benzyl-β-D-ribofuranoside (1) is described. Methyl 5-O-benzyl-3-deoxy-3-fluoro-β-D-xylofuranoside (3) and methyl 5-O-benzyl-3-deoxy-3-fluoro-α-D-arabinofuranoside (11) were converted, via the 2,5-di-O-benzoyl derivatives (6) and (12), into the correspondingαβ-D-glycosyl bromides (7) and (13). The latter compounds were then condensed with 6-benzamidopurine to yield the fluorinated nucleosides, 6-benzamido-9-(2,5-di-O-benzoyl-3-deoxy-3-fluoro-β-D-xylofuranosyl)purine (8) and 6-benzamido-9-(2,5-di-O-benzoyl-3-deoxy-3-fluoro-α-D-arabinofuranosyl)purine (14), respectively. Structural assignments of the fluoronucleosides (8) and (14) were based upon u.v. comparison with known 9-(3-deoxy-β-D-pentofuranosyl)adenines, and the fact that, on alkaline hydrolysis, compounds 8 and 14 yielded crystalline fluoronucleosides (9) and (15) which gave the 5′-toluene-p-sulphonates 10 and 16; on heating, compound 10 formed a 3,5′-cyclic p-toluenesulphonate, whereas compound 16 did not. These results are consistent with the anomeric configuration assigned to 9-(3-deoxy-3-fluoro-β-D-xylofuranosyl)adenine (9) and 9-(3-deoxy-3-fluoro-α-D-arabinofuranosyl)adenine (15). n nThis synthesis of deoxyfluoronucleosides is considered to be less limited in application than those so far reported.

Fluorocarbohydrates : Part XVI. The synthesis of 3-deoxy-3-flouro-D-xylose and 3-deoxy-3-fluoro-β-D-arabinose

Abstract The action of potassium hydrogen fluoride (KHF 2 ) in ethane-1,2-diol on methyl 2,3-anhydro-4- O -benzyl-β- D -ribopyranoside ( 1 ) and methyl 2,3-anhydro-5- O -benzyl-α- D -lyxofuranoside ( 7 ) has been examined. In both cases the expected trans scission of the epoxide ring occurs to yield methyl 4- O -benzyl-3-deoxy-3-fluoro-β- D -xylopyranoside ( 2 ) and methyl 5- O -benzyl-3-deoxy-3-fluoro-α- D -arabinofuranoside ( 8 ) respectively. The structure of compound ( 2 ) was established by catalytic hydrogenation, which removed the benzyl group, to yield a crystalline glycoside ( 3 ) which did not consume periodate. Acid hydrolysis of methyl 3-deoxy-3-fluoro-β- D -xylopyranoside ( 3 ) yielded syrupy 3-deoxy-3-fluoro-αβ- D -xylose ( 5 ) as a syrup characterized as the 2,5-dichlorophenylhydrazone. Acid hydrolysis of compound ( 8 ) yielded a reducing sugar ( 9 ), characterised as the phenylhydrazone. Compound ( 9 ) consumed 1 mol. of periodate and liberated formic acid which is consistent with the structure 5- O -benzyl-3-deoxy-3-fluoro-αβ- D -arabinose. Catalytic hydrogenation of the fluorohydrin ( 8 ) removed the benzyl group to give methyl 3-deoxy-3-fluoro-α- D -arabinofuranoside ( 10 ) which, on acid hydrolysis, yielded crystalline 3-deoxy-3-fluoro-β- D -arabinose ( 13 ). The β-configuration was assigned to compound ( 13 ) on the basis of its mutarotation. This method of introducing fluorine into carbohydrates affords reasonable yields of uncontaminated fluorohydrins and is considered to have general applicability.

Quantitative determination of fluorinated carbohydrates and related compounds in biological materials

Abstract A rapid and accurate method for the estimation of a group of fluorinated carbohydrates and other fluorinated compounds of biological interest is described. It is based on the release of fluoride ion from covalent bonding by an alkaline digestion with subsequent measurement of the ion with a specific fluoride electrode. No diffusion or extraction of fluoride is required and the estimation can be carried out in the presence of significant concentrations of yeast cells. In addition the method allows the estimation of fluorinated materials when incorporated into yeast cells.

The synthesis and reactions of unsaturated sugars : Part II. Introduction of endocyclic double bonds into pentoses and hexoses

Abstract The action of sodium iodide in acetone on methyl 4- O -benzyl-3-deoxy-3-iodo-2- O -tosyl-β- l -xylopyranoside ( 1 ) is described. At room temperature, methyl 4- O -benzyl-2,3-dideoxy-β- l - glycero -pent-2-enoside ( 2 ) and methyl 2- O -benzyl-3,4-dideoxy-β- l - glycero -pent-e-enoside ( 2a ) were formed. At lower temperatures (0–5°), the action of sodium iodide in acetone on 1 produces only the expected 2,3-alkene 2 , and a mechanism, based on conformational analysis, is suggested to account for this fact. The action of sodium iodide in acetone on methyl 4- O -benzyl-3-deoxy-3-iodo-2- O -tosyl-6- O -trityl-α- d -glucopyranoside [ 12 , made from the iodohydrin 9 obtained by the action of methylmagnesium iodide on methyl 2,3-anhydro-4- O -benzyl-6- O -trityl-α- d -allopyranoside ( 8 )] is also described. The structure of the iodohydrin 9 was established by mild, acid hydrolysis, followed by sequential hydrogenolysis, to yield methyl 3-deoxy-α- d - ribo -hexopyranoside. Treatment of 12 with sodium iodide in refluxing acetone yielded a crystalline alkene, which has an n.m.r. spectrum consistent with the structure of methyl 4- O -benzyl-2,3-dideoxy-6- O -trityl-α- d - erythro -hex-2-enoside ( 13 ). This structure was further confirmed by cis hydroxylation of 13 with neutral potassium permanganate, followed by catalytic hydrogenolysis, to give methyl α- d -mannopyranoside.

Effect of 3-deoxy-3-fluoro-d-glucose on glycolytic intermediates and adenine nucleotides in resting cells of Saccharomyces cerevisiae

Abstract The effects of 3-deoxy-3-fluoro- d -glucose (3FG ∗ ) upon the levels of glycolytic intermediates, adenine nucleotides and inorganic phosphate in resting cell suspensions of Saccharomyces cerevisiae have been investigated. Significant decreases in the intracellular levels of UDPG, PGAs, ATP and inorganic phosphate were detected whilst increases in ADP, G-1-P and F-6-P were observed. The changes in ATP, ADP and G-1-P only became apparent after the changes in the other intermediates had occurred. It is argued that 3FG acts at least in part as a phosphate trap thereby occasioning a shift in the energy balance of these cells.

Oxidation of 3-deoxy-3-fluoro-D-glucose by cell-free extracts of Pseudomonas fluorescens.

Abstract The oxidation of 3-deoxy-3-fluoro- d -glucose (1) and 3-deoxy-3-fluoro- d -gluconic acid (2) by a cell-free extract of Ps. fluorescens proceeds with the consumption of 2 g-atoms and 1 g-atom of oxygen/mole of substrate respectively. The localization of the oxidizing system is considered to be in a particulate fraction and evidence is presented which indicates that the oxidation of the fluorinated substrates (1) and (2) is by the glucose-gluconic acid enzyme system. The difference observed between the extent of oxidation of 3-deoxy-3-fluoro- d -glucose by whole cell and cell-free extracts of Ps. fluorescens is discussed.