D Mannose: What Is It?

D-mannose (also known as D-(+)-mannose; D(+)-mannose) with the molecular formula C6H12O6 and relative molecular mass of 180.16 is an isomer of glucose and galactose.D-mannose, as a simple monosaccharide, exists in a wide range of forms, and is a component of most polysaccharides. D-mannose is a simple monosaccharide that occurs in a wide variety of forms and is a component of most polysaccharides. D-mannose is also present in large quantities in oligosaccharides in plants and cell walls. Free D-mannose is found in peaches, apples, and orange peels, and D-mannose-containing glycans are found in large quantities in Ivory Palm, Serum Globulin, Egg Mucins, Red Algae, Yeast, and Mycobacterium Tuberculosis [1]. Due to its wide elemental distribution, D-mannose is often found in glycan research.

From the 1960s to the present day, sugar-related disciplines (sugar engineering, glycobiology, and glycochemistry) have developed tremendously, and people's understanding of sugar has evolved from an energy source for life and the structure of the material composition to the important biological functions of sugar, such as immunomodulation and anti-inflammatory functions [2]. One of the polysaccharides that has been the subject of much research contains D-mannose as a component. Studies have shown that D-mannose has the ability to prevent wound inflammation and reduce granulation tissue formation in experimental wound models[3] . Meanwhile, in a study by Yue Jianxiong[4] , D-mannose was found to be used as a screening agent for labeling genetically transformed cells.

In the human body, D-mannose is not well metabolized and is distributed in body fluids and tissues, especially in nerve and skin tissues, as well as in the liver and intestines, where it is abundant. D-mannose is indispensable for immune regulation and glycoprotein synthesis in the human body, and when the human body suffers from a disease, it may be caused by a lack of the enzyme involved in the glycation of D-mannose. Therefore, D-mannose is often added to glyconutrients used in clinical practice[1] . D-mannose is important for human health and has a variety of physiological effects: it promotes wound healing, inhibits cancer cell survival and tumor growth, prevents bacterial infections in the urinary tract, promotes immune system regulation, has anti-inflammatory effects, and captures antigens by the four traps on the surface of macrophages containing D-mannose[2] . antigen capture [1,5,6].

Currently, there are many reports on D-mannose and its applications are very extensive. In the food industry, D-mannose is often used as a sweetening additive in health products and beverages; in medicine, D-mannose can be used for the modification of cancer drugs to achieve the purpose of targeted drug delivery; in the aquaculture industry, D-mannose can be used in feeds to prevent Salmonella infections in broiler chicks and to improve egg production; in chemical synthesis, D-mannose can be used as a raw material for the synthesis of a wide range of derivatives, such as trifluroxypropionate and L-ribose, etc. [1,4,5]. In chemical synthesis, D-mannose can be used as a raw material to synthesize various derivatives, such as trifluoromannose and L-ribose, etc.[7] , and its wide range of applications makes D-mannose has good economic value and market prospects.

1 Properties of D-mannose

1.1 Physical properties of D-mannose

D-mannose is soluble in water, slightly soluble in ethanol, insoluble in ether. Its pure product is white crystal or powder, sweet, slightly bitter taste, melting point is 132 ℃ (α-type crystalline) ~ 133 ℃ (β-type crystalline), D-mannose of the two configurations α-type (methyl of the crystal) β-type (ethyl of the crystalline) in aqueous solution than the rotational degree of the [α]D20 +29.3→ +14.6 °, [α]D20- 29.3→ +14.6 °, [α]D20- +14.6 °, [α]D20- +29.3→ +14.6 °, [α]D20- +29.3→ +14.6 °. 29.3→ +14.6°.

1.2 Chemical properties of D-mannose

D-mannose is a kind of reducing monosaccharide, with reducing property, under the action of alkaline weak oxidizing agent, it generates metal or metal low-valent oxides, and under the action of acid oxidizing agent, it generates mono- or di-D-mannuronic acid, or it generates formic acid and methanol, D-mannose can also interact with alcohol or molecules with hydroxyl groups to generate glycosides, and at the same time, the multiple hydroxyl groups of D-mannose can also generate esterification reaction with acid. When D-mannose interacts with trimolecular phenylhydrazine, D-mannoside is formed. D-mannoside has a characteristic crystalline shape and a certain melting point, and the properties of glycoside can be used to identify D-mannose. When the reducing agent and D-mannose action, D-mannose is reduced to D-mannitol. D-mannitol is a hypertonic tissue dehydrating agent, has been widely used in clinical. 2 D-mannose application.

2 Application of D-mannose

2.1 Application of D-mannose in foods

D-mannose is often used as a sweet substitute for sucrose due to its sweetness and low-calorie properties. Until now, D-mannose has been consumed directly as a food supplement. Currently, edible D-mannose is produced in the United States and China, and the best-selling brands of D-mannose include Source Naturals, Vibrant Health, and NOW Foods, where D-mannose is mostly available in capsule or powder form [8]. In addition, D-mannose is used commercially in food products because of its texture-enhancing properties, such as its solubility and anti-melting properties, which are widely used in commercial ice creams. At the end of the 20th century, Elghaouth and Wilson et al [9] found that the inoculation of D-mannose in apples or peaches that were about to rot could reduce the diameter of the rot spots, and at the beginning of the 21st century, Yang Bingxun et al [10] determined the D-mannose content of Dendrobium ferrugineum beverage, which is a beverage with the function of improving the immune system, by using the HPLC method, and it is a benchmark calibration for the control of quality of the beverage of this kind of Dendrobium ferrugineum. This method was used as a benchmark for quality control of Dendrobium beverages.

2.2 Application of D-mannose in medicine

In medicine, D-mannose is often used to treat the corresponding diseases with its various physiological functions. When D-mannose is combined with some anticancer drugs (adriamycin) to form a targeted drug in the form of a polymerized bundle gel, it can be used in the human body to provide targeted treatment of cancer and to reduce the toxic side effects of cancer drugs on human tissues [11]. Meanwhile, in the study of Ranta [12], D-mannose can be used as a raw material to synthesize Candida albicans β-(1→2)-linked cell wall mannan with D-glycan structure, which is a kind of immunostimulant, and Kamel [13] synthesized a new type of Schiff base by using D-mannose as a raw material, and the results proved that it has a certain antitumor activity. In addition, D-mannose can be used as a novel method to modulate spinal immune cells to a phagocytic phenotype to improve non-toxic gene therapy, and to inhibit abnormal pain effects during peri-spinal therapy [14].

2.3 Application of D-mannose in aquaculture

For a long time, the growth of livestock and poultry as well as the prevention and treatment of diseases in the aquaculture industry have relied on antibiotics, but the excessive use of antibiotics can cause environmental pollution or the proliferation of drug-resistant bacteria [15,16]. Therefore, it is important to find alternatives to the use of antibiotics. In the 1990s, researchers in the United States tested D-mannose and several other sugars on Salmonella typhimurium-treated young chickens and found that D-mannose could inhibit Salmonella infection in young chickens, and that D-mannose had no adverse effects and could be an alternative to antibiotics for this bacterium [16,17].

In addition, it was found that D-mannose has the effect of hindering the colonization of pathogens in the intestinal tract and making them fall off, and it can be widely used in livestock and poultry feed to inhibit the proliferation of pathogens [18].

2.4 Application of D-mannose in the synthesis of derivatives

2.4.1 Synthesis of trifluoromannose

D-mannofuranose, also known as trifluorosulfonate, can be used as an organic precursor to synthesize a variety of derivatives, among which 18F-FDG (fluorine 18F deoxyglucose injection for positive-ion radiopharmaceuticals) has been widely used in clinical practice, which is of great significance for the safe use of drugs in clinical practice [19]. However, at present, most of the trifluoromannose in China is imported from abroad, and the price is expensive, which brings inconvenience to the clinical diagnosis of PTE in major hospitals. Therefore, it is of great significance to design a reasonable synthesis route of trifluoromannose. Yang ZJ et al [20] found that the yield of trifluoromannose was 46% after acetylation, selective hydrolysis and sulfonation of D-mannose as raw material, and the purity of trifluoromannose could reach 99% after purification. The experiment proves that the synthesis route is feasible, and the product with high purity can meet the market demand.

2.4.2 Synthesis of L-ribose

Ribose is an important component of ribonucleic acid (RNA) in nature, which plays an important role in the genetic and physiological regulation of organisms. In nature, ribose exists in the form of D-ribose, and L-ribose is an isomer of D-ribose, which has good anti-tumor and viral effects and low toxicity to tissue cells[21] . However, L-ribose does not exist in nature, so it is important to obtain large amounts of L-ribose through chemical synthesis [21,22]. It was found that D-mannofuranosyl-1,4-lactone, synthesized from D-mannose, was well converted to L-ribose. Takahashi et al. [22,23] reported that D-manno-1,4-lactone was converted to L-ribose in eight steps, including cyclization under Mitsunobu conditions, and Seo et al. [22,24] used D-manno-1,4-lactone as a raw material to convert L-ribose in one-pot reversal conditions with good yields.

2.5 Other applications of D-mannose

2.5.1 Application to cosmetics

In today's society, cosmetics are indispensable consumer products in most women's daily life. Aloe vera, as a kind of early plant with the functions of beauty, sunscreen and moisturizing, has an important position in the cosmetic industry [25]. Aloe vera polysaccharides have been found to be the main physiological active substances in Aloe vera, and their main components are long-chain polymers of β-(1→4)-mannans and glucomannans [26]. Among them, D-mannose has been shown to be effective in skin conditioning, making the skin feel less tight or dry, softer and smoother after washing [27]. In the 1990s, Wivell et al [28] invented a composition for skin cleansing and skin moisturizing with beneficial effects, which consisted of D-glucose in a molar ratio of 2.8:2.0:2.0, D-mannose and D-glucuronide. mannose and D-glucuronic acid in a molar ratio of 2.8:2.0:2.0.

2.5.2 Application in biochemical research field

As a carbohydrate chemical, D-mannose not only has various physiological functions in living organisms, but also provides energy. It has been found that D-mannose, as a cellular screening agent for labeling transgenes, has been successfully transformed into potato, sugar beet, wheat and maize, among which the transformation of sugar beet has a very low selective pressure, and up to 30% of the explants can be germinated [29]. The antibiotic-resistant transgenic screening agent has been replaced by D-mannose for transgenic plant research, and studies have shown that D-mannose-resistant cells have been used in hundreds of primary transgenic rice plants under different cultivation conditions [29]. In addition, in the work of Wang [30], D-mannose was found to provide a carbohydrate source for maize healing tissues and could be used for protoplast transformation in maize polyethylene glycol media.

3 Market prospects of D-mannose

D-mannose, as a simple hexose, exists in a wide range of forms and applications. In the industrial food industry, D-mannose can be used as a substitute for high-calorie sugar and as an auxiliary agent in a variety of new food products, which has great market value. Secondly, in the breeding industry and biochemical research, D-mannose's environmental protection and safety characteristics have also made the field better developed. Meanwhile, the application of D-mannose in the research and development of daily chemical products not only reduces the cost of the products, but also its naturalness and good skin-care effect will lead to a large amount of economic consumption and bring considerable economic benefits to enterprises. Due to its structural properties, D-mannose can be used in the synthesis of a variety of derivatives and as a coupling agent for the synthesis of important compounds for the development of scientific properties and applications. As in medicine, D-mannose is used in drugs with greatly increased properties, which are important for anti-inflammatory, anti-cancer and anti-tumor drug research. So far, many research results have been achieved in this field, but the road to research is still bumpy, and we believe that a large number of researchers will join the camp in the future.

References

[1] Cheng Z. Research on low temperature thermodynamic properties and thermal decomposition kinetics of monosaccharides[D]. Shenyang: Shenyang University of Technology,2016.

[2]Pan Ziguo.Research on the extraction and purification process of D-mannose[D]. Hangzhou: Zhejiang University, 2009.

[3]Kössi J,Peltonen J,Ekfors T,et al.Effects of hexose  sugars: glucose,fructose,galactose and mannose on wound healing in the rat[J].European Surgical Research, 1999,31(1):74-82.

[4] YUE Jianxiong, MENG Zhaohong, ZHANG Lianhui, et al. Genetic transformation of cotton using mannose as a screening agent[J]. Journal of Cotton, 2005(1):3-7.

[5]Mazumder P,Mukhopadhyay C.Conformations,dynamics and interactions  of di-,tri-  and pentamannoside with mannose binding lectin:a molecular dynamics study[J].Carbohydrate Research,2012,349:59-72.

[6]Taguchi,T.Determination of D-Mannose in Plasma by HPLC [J].Clinical Chemistry,2003,49(1):181-183.

[7] LIANG Zhi,HUANG Guohong. Preparation and use of mannose[J]. Friend of Chemical Industry,2000(3):14.

[8]Hu X,Shi Y,Zhang P,et al.D-Mannose:properties,production, and  applications:an  overview[J].Comprehensive  Reviews  in Food Science & Food Safety,2016, 15(4):773-785.

[9]El G A,Wilson C L,Wisniewski M.Sugar analogs as potential fungicides for postharvest pathogens of apple and peach. [J].Plant Disease, 1995,79(3):254.

[10] YANG Bingxun, SHEN Chunxiang, WANG Zeng, et al. Determination of D- glycopyranose in Dendrobium officinale beverage by HPLC[J]. Food Science,2011(8):275-277.

[11] Wang Shuting.Targeted drug delivery study of D-mannose modified polymeric micelles [D]. Wuxi:Jiangnan University,2015.

[12]Ranta  K,Nieminen K,Ekholm  F S,et  al.Evaluation  of immunostimulatory activities of synthetic mannose- containing Structures mimicking the β-(1→2)-linked  cell wall mannans of Candida albicans[J].Clinical and Vaccine Immunology,2012, 19(11):1889-1893.

[13] Kamel M M,Ali H I,Anwar M M,et al.Synthesis,antitumor activity and molecular docking study of novel Sulfonamide- Schiff’s  bases,thiazolidinones,benzothiazinones  and  their C-nucleoside derivatives[J].European Journal of Medicinal Chemistry,2010,45(2):572-580.

[14] Dengler E C,Alberti L A,Bowman B N,et al.Improvement of spinal  non-viralIL-10gene  delivery  by  D-mannose  as  a transgene adjuvant to control chronic neuropathic pain[J]. Journal of Neuroinflammation,2014, 11(1):92.

[15] WANG Ran,LIU Tiezheng,WANG Tian. The fate of antibiotics in the environment and their ecotoxicity [J]. Journal of Ecology,2005,26(1):265-270.

[16] Van I F,Cauwerts K,Devriese L A,et al.Feed additives to control Salmonella in poultry[J].World's Poultry Science Journal,2002,58(4):501-513.

[17] Zhang Zhaofu.D-mannose inhibits Salmonella infection in broiler chicks[J]. Livestock and poultry industry,1998(11):18.

[18]Berge A C,Wierup M.Nutritional strategies to combat Salmonella in mono-gastric food animal production[J]. Animal,2012,6(4):557-564.

[19]FENG Miao, YU Jingjing,YIN Changfeng,et al. Study on the examination method of bacterial endotoxin by trifluoromannose[J]. Chemical Reagents,2017,39(9):992-994.

[20]YANG Zhijie,ZHOU Saichun. Synthesis of diagnostic reagent trifluoromannose[J]. Journal of Chemical Industry, 2004(7):34-35.

[21] Zhan Yijing, Xu Zheng, Xu Lu, et al. Advances in the production of L-ribose[J]. Bioprocessing,2013,11(5):74-78.

[22] Zou Ye, Su Weike. Progress in the synthesis of L-ribose[J]. China Pharmaceutical Industry Magazine,2018,49(8):35-47.

[23]Takahashi  H,Iwai  Y,Hitomi  Y,et  al.Novel  synthesis  of L-ribose   from   D-mannono-1,4-lactone[J].Organic   Letters, 2002,4(14):2401-2403.

[24]Seo   M   J,An   J,Shim   J   H,et    al.One-pot   inversion   of d-mannono-1,4-lactone   for   the    practical    synthesis   of l-ribose[J].Tetrahedron Letters,2003,44(15):3051-3052.

[25] ZHANG Qiang, CUI Jun, GU Hua, et al. Determination of aloe vera glycosides in cosmetics and study of their stability[J]. Daily Chemical Industry,2019,49(3):199-202,208.

[26] HE Jie, FAN Zhenjing. Research progress of Aloe vera polysaccharides[J]. Huaxia medicine,2017,30(2):188-191.

[27]Schmidt  R  R,Fortna  R H,Beyer H H.Mild  skin cleansing aerosol mousse with skin feel and moisturization benefits [P].US:5002680, 1991-3-26.

[28]WivellSC,DecknerGE.Combinedpersonal cleansing and moisturizing compositions[P].US:5439682, 1995-8-8.

[29]Joersbo  M.Advances  in the  selection  of transgenic plants using non-antibiotic marker genes[J].Physiologia Plantarum, 2001, 111(3):269-272.

[30]Wang  A  S,Evans  R  A,Altendorf  P  R,et  al.A  mannose selection system for production of fertile transgenic maize plants  from  protoplasts[J].Plant  Cell  Reports,2000, 19(7): 654-660.