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2-Deoxy-D-Glucose

Summary

2-Deoxyglucose is a rare and natural monosaccharide that can be made from D-glucose, D-aminoglucose and some amino-polysaccharides. 2-DG exhibits various physiological and pharmacological effects on antivirus, anti-cancer and anti-aging. It has great potential in medicine, foods, and cosmetics.

Key Words: 2-DG

Preparation

Therapeutic effect

Application

2-Deoxyglucose (2-DG) is also called 2-deoxy-D-glucose, 2-deoxy-D-arabino-hexose or D-arabino-2-deoxyhexose. It is the basic structure of the anticancer drugs such as daunomycin, adriamycin, carminomycins and antibiotics with lactonic ring.

2-DG can be prepared from D-glucose, D-mannose, D-gluconic acid, D-arabinose, chitin and its derivatives. It has physiologic and pharmacologic effects, so it has great potential in medicine, healthcare, cosmetics, and life science research. This paper summarizes the preparation, characteristic properties, physiological and pharmacological effects as well as medical applications.

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1. Preparation of 2-DG

2-DG can be prepared from different starting materials such as D-glucose, D-mannose, calcium D-gluconate, D-arabinose, D-glucosamine hydrochloride, N-acetyl glucosamine, chitin, and chitosan and carboxy methyl chitosan. Preparation methods vary with various starting materials, and various chemical reactions. Therefore there are dozens manufacturing process to prepare 2DG. For example, Bergmann, et. al.3 methylated and bromonated the D-glucose followed with debromonation and hydrolysis with acid to obtain ß-2-DG. Other 2DG preparation included treated D-glucose or D-mannose with bromine and acetyl, followed by Fischer4 procedure to prepare 3,4,6-tri-O-acetyl-1,5-anhydro-2-deoxy-D-arabino-hex-1-enitol. Then, bromine was added and reduced to remove acetyl group yielding 2DG5. Monneret6 treated 3,4,6-tri-O-acetyl-1,5-anhydro-2-deoxy-D-arabino-hex-1-enitol with N-bromosuccinimide followed by hydrogenation and deacetylation to obtain 2-DG. Wong, et. al.7 reacted D-glucose with ethanethiol, benzoyl chloride, followed by dehydrogenation, reduction, deprotection to give 2-DG. But this reaction contains too many steps with low yields. Overend8 deacetylated glucal with sulfuric acid to give 2-DG with overall yield of 35%. Sowden, et.al9 developed a method involving the treatment of D-arabinose with nitromethane and an acetylating agent. a-2-DG was obtained by treatment with diluted sodium hydroxide, with an overall yield of about 25%. Shiue, et.al.10 condensed and reduced D-arabinose with acetone, then reacted with trifluoromethanesulfonic anhydride. The product was reacted with sodium cyanide and then after hydrogenation, reduction and hydrolysis yielding 2-DG.

D-arabonose is also a rare natural single sugar, but can be made by oxidizing and removing carboxyl from d-glucose acidic calcium. Also, crudes with 2DG in it can be derived by removing aminofrom glucosaminol, amino glucoside and amino saccharide by using hydroxylamino-O-Sulfonic acid (HOS).

Chitin and chitosan,after being removed amino by using HOS, can also produce poly 2dg fiber. After removing animo with HOS, carboxymethyl chitosan produces poly carboxymethyl 2dg. Publications 11, 12 also reported that by removing chloride ion,

glucosaminal, removing amino by using acety nitrous acid has a yield of 55.14%.

Aspinall 13 et al after treating N-acetyl - d - glucosamine with hydrogenation, then treated with hydrazine sulfate, and removing amino using nitrous acid, also get 2dg. but with complicated processes and yields at least eight other substances, in which the yield of 2 deoxy d glucose is 44.4%.

Amarp 14 et al respectively used alpha and better D - mythyl - glucosamineside hcl react with HOS, produced corresponding alpha and beta - 2 dg and b - 2 deoxy - methyl – glucoside, yield are respectively 55% and 31%.

After removing amino using HOS, N-deacytyl-pneumonia streptococcus, 14 spore saccaride and chloero vibio - O - antigen saccaride, yield in weight is respectively 90% and 55%, in which 2dg ratio is respectively 55% and 60%. Based on Doldouras reaction principle, 15, glucosamine hcl reacting with HOS can also yield 2dg. This author also obtained 2dg by using free glucosaminol reacting with nitrous acid?At the same time, we used chitosan, chitin and carboxymethyl chitosan reacting with HOS, we also successfully obtained corresponding 2dg. The latter all have fiber properties and not soluble in water, is not soluble even in 2mol/LHCL flux.

But using nitrous acid and HOS to remove amino from methyl amino glucoside, glucosaminol amino sugar and amino poly saccaride is a very complicated process involving enol rearrangement, other relocation of gene group and Walton reversal, is therefore not clearly defined, thus complicated side products are produced.

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2. 2-DG Basic Chemical Characteristics

Molecular formula: C6H12O5

Molecular weight (MW): 164.6

Elemental composition: C 43.90%, H 7.37%, O 48.73%

2-DG is a white crystalline hydroscopic powder. It is odorless, tastes sweet and very soluble in water, partially soluble in hot methanol, ethanol, acetone, and butanol. It is not soluble in ether, chloroform, petroleum ether and toluene. 2-DG is a polyhydroxy aldehyde with reducing ability can react with Fehling or Benedict reagent and produce red or yellow precipitation of copper oxide. It can be reacted with aniline to give 2-deoxy-D-glucose aniline which is soluble in hot alcohol8. 2-DG can react with benzylphenyl hydrazine to form 2-DG benzyl phenyl hydrazone[9]. Besides, 2-DG can be a or ß form with different melting point and optical rotation. Using different material and different procedure will result in different forms or a mixed form with different ratios. The melting point, optical rotation, reducing capability and chromatographic behavior will be different. 2-DG made from D-arabinose yields a-2-DG. The melting point (mp) of the first purified material was 128C -129C and was 123C -125C after recrystallization, indicating some a-forms were changed to ß-forms. In the meantime 2-DG gradually changed its optical rotation with time. In the water, [a]D23-25 was changed from +53.8?(10 min) to +50.3?(20 min) ?48?(30 min) ?46.6?(1 h, constant)

a-2-DG recrystallized from isopropanol has a mp of 134?-136? In pyridine, [a]D26 was from +156??+103?(C 0.9). 2-DG16 prepared from D-glucose has mp of 142?-144? Melting point of 2-DG, made from glucal, treated with diluted sulfuric acid and recrystallized from methanol and acetone, was 146°. In water, [a]D17.5 was from +38.5??+ 45.9?(within 35 min) (C 0.5). In pyridine, [a]D17.5 was from +22.8??+80.8?(within 24 h) (C 0.57). Therefore some physico-chemical parameters are usually different if 2-DG is prepared from different starting material or different process.

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3. Physiological and Pharmacological Effects

2-DG acts to inhibit the phosphorylation of a glucose molecule that produces glucose-6-phosphate in the glycolysis cycle, therefore inhibiting the production of ATP and can also decrease the temperature in muscle cells. It can restrain viral infections and fermentation, microbes and cancer cell growth. It also controls metabolism and possesses physiological and therapeutically effects. These effects can be change the polysaccharides of viruses and lose its infectious influence and inhibit viral proliferation. Richard17 reported that 2-DG can inhibit the growth of RNA in viruses (specifically the herpes simplex virus (HSV)) greater than 90% in 0.1-0.3% concentration. However, if the concentration increased, HSV infection tested in African green monkey kidney cell (BSC1) will develop a resistance to 2-DG. If the concentration of 2-DG increased to 0.1% and 1%, the prohibition rates were 94% and 99%, respectively.

Many different experiments have been complete to discover the usage of 2-DG. In the experiment of infecting chicken embryos with the influenza virus, it has been found that you can use 12.5-25 mg of 2-DG, with increased inhibition of 89%-97%. In another animal test, if you inject 2-DG to animals, it can decrease episodes of epilepsy. Therefore, it explains that 2-DG can protect the central nervous system. Another test showed that 2-DG can lower glucose levels in the blood, as well as glucose levels in brain. Another effect of 2-DG is the ability to activate the sympathetic nervous system, as it has been found that heart rate accelerated and skin temperature elevated. Also, 2-DG inhibits glucose metabolism in muscle, resulting in skeletal muscles relaxed, blood vessels dilated and blood circulation accelerated. This blood vessel dilation is not affected by the ATP dependency upon K+ channel.

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4. Application

2-DG is antimetabolic antibiotics. It acts as anti-viral, anti-bacterial, anti-cancer, anti-epilepsy and anti-aging agents. It is used to prevent viral and bacterial infections and infectious diseases such as HSV, HIV, SARS, influenza, and hepatitis B. It has been widely studied for antiviral agent for a long time and possible to be one of the antiviral drugs. In addition, 2-DG can also help protect the central nervous system and prevent occurrences of epilepsy. For a long time in Chinese history, many empires and Daoism followers were trying to seek a wonder drug to prolong the life or live forever. Up to now, nobody has successfully developed such drug. 2-DG has the potential to fulfill this dream to prolong life. In experiments that were performed on monkeys and mice, it has been found that 2-DG can prohibit metabolism of sugar, decrease glucose levels in blood and brain. It promotes the accumulation of liver sugar and lowers the production of ATP and toxins. 2-DG increases relaxation of muscles, dilates blood vessels, decreases triglyceride levels, and maintains young testosterone levels in the body. It delays the metabolic process of cells and decreased the cell duplication20. It maintains the normal cells in a steady state, prolongs their survival time, minimizing blood vessels hardening (atherosclerosis). 2-DG reduces the occurring rate and time for the high blood pressure, heart disease, diabetes, cancer, and other diseases associated with aging. Therefore, 2-DG is one of the key anti-aging materials studied by the scientist. It is likely that 2-DG can potentially become a good anti-aging drug. Now, people think 2-DG is a low toxicity material. 2-DG is safe when low quantity is used. However, 2-DG is toxic in animals when used in high dose for long treatment. The issue is that the effective dose is close to the toxic dose. It is believed the wonder drug to improve health and aging can be developed with the help of modern science and technology with advanced dosage and scientific procedures.

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5. Conclusion

2-DG is an anti-metabolic glucose. It is also a rare and natural antibiotic mannose. It was first prepared from D-glucose in 1922. From then on, many scientists around the world have been studied from various prospects on the preparation process and physiological and pharmacological effects. It was found 2-DG can prohibit the growth of virus, bacteria and cancer cells. It also reduce the frequency of epilepsy, reduce its mortal rate, but also limit glucose metabolism in muscle, reducing energy creation, enlengthen life span. Therefore it has wide promising future in pharmaceutical, nutraceutical and cosmetic industries. But because there are still difficulties in producing methods, there is rare commercialization of this product, thus limiting its application in the marketplace. Therefore there is a need for further study of this product.

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References

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