Publisher Summary This chapter presents a review about the chemistry and developments of fluorinated carbohydrates. 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. Deoxyfluoro sugars labeled with fluorine-18 have important applications as imaging agents. Numerous 5-fluorouracil derivatives have been prepared as potential anticancer agents. Fluorine-18 is not known naturally (natural fluorine is all 19 F), but it may be prepared in a variety of artificial nuclear reactions. Several 1-phosphates of deoxyfluoro sugars have been prepared and their acid-catalyzed hydrolysis has been studied. The fluorination of aminoglycosides and anticancer antibiotics has been undertaken to obtain the derivatives of enhanced activity and decreased toxicity. The knowledge concerning the conformation of nucleosides is important in pursuing the relationship between the structure and biological activity of compounds containing fluorinated carbohydrates. Much effort has been devoted to preparing natural nucleoside analogs having effective antiviral (mostly antiherpetic) and antitumor activities with low cytotoxicity for the host cells.

Chemistry and Developments of Fluorinated Carbohydrates

Synthesis of Fluorinated Carbohydrates

The synthesis and hydrolysis of a series of deoxyfluoro-d-glucopyranosyl phosphates

Microbial cleavage of CF bond

There are presently many methods of detecting complex carbohydrates, and particularly glycogen. However most of them require radioisotopes or destruction of the tissue and hydrolysis of glycogen to glucose. Here we present a new method based on the incorporation of 2-NBDG (2-{N-[7-nitrobenz-2-oxa-1, 3-diazol 4-yl] amino}-2-deoxyglucose), a d-glucose fluorescent derivative, into glycogen. Two kinds of approaches were carried out by using Clone 9 rat hepatocytes as a cellular model; (1) Incubation of cell lysates with 2-NBDG, carbohydrate precipitation in filters and measurement of fluorescence in a microplate reader (2) Incubation of living hepatocytes with 2-NBDG and recording of fluorescence images by confocal microscopy. 2-NBDG labeled glycogen in both approaches. We confirmed this fact by comparison to the labeling obtained with a specific monoclonal anti-glycogen antibody. Also drugs that trigger glycogen synthesis or degradation induced an increase or decrease of fluorescence, respectively. This is a simple but efficient method of detecting glycogen with 2-NBDG. It could be used to record changes in glycogen stores in living cells and cell-free systems and opens the prospect of understanding the role of this important energy reserve under various physiological and pathophysiological conditions.

"Fluorescent glycogen" formation with sensibility for in vivo and in vitro detection.

An alternative synthesis of 4-deoxy-4-fluoro-D-glucose and its transport in the human erythrocyte.

Flight muscle and fat body extracts fromLocusta migratoria were incubated with D-[U-14C]-glucose or D-[3-3H]-3-deoxy-3-fluoroglucose and the products were analyzed. In the case of the latter compound, radio-chromatographic analysis yielded glycogen and trehalose fractions that were shown by19F nuclear magnetic resonance to contain fluorine. Acid hydrolysis of these fractions liberated tritium labelled 3-deoxy-3-fluoro-D-glucose. In addition to the formation of “fluoroglycogen” and “fluorotrehalose” in these tissue extracts, there was an accumulation of tritium labelled fructose.

Norman F. Taylor

Papers

An alternative synthesis of 4-deoxy-4-fluoro-D-glucose and its transport in the human erythrocyte.

Incorporation of 3-deoxy-3-fluoro-D-glucose into glycogen and trehalose in fat body and flight muscle in Locusta migratoria.

The defluorination of 4-deoxy-4-fluoro-D-glucose in the cytoplasmic membrane of Pseudomonas putida

The metabolism of 4-deoxy-4-fluoro-D-glucose in Pseudomonas putida

Synthesis of 4-deoxy-4-fluoro-d-[6-3H]glucose