1,2,3,4-Di-O-isopropylidene-a-D-fucopyranose

二-O-异丙叉-alpha-D-岩藻糖; 双丙酮-D-岩藻糖

1,2:3,4-Di-O-isopropylidene-a-D-fucopyranose is a tailored drug that was developed to have the same chemical structure as endogenous natural fucopyranosides. It has been shown to be a potent inhibitor of bacterial growth in vitro. The drug has been shown to have anti-inflammatory effects in vivo and may be useful for the treatment of autoimmune diseases. 1,2:3,4-Di-O-isopropylidene-a-D-fucopyranose has been observed to inhibit the production of inflammatory cytokines such as IL1β and TNFα by macrophages at concentrations of 10 μM or less. It has also been shown to inhibit NFκB activation by inhibiting IκB kinase activity.

1,2,3,4-Di-O-isopropylidene-alpha-D-fucopyranose (also known as Di-tert-butyl fucose) is a synthetic compound used in various biological studies related to fucosylation, glycan binding and synthesis. Fucosylation (the attachment of fucose sugar to glycan chains) is critical in many biological processes like cell-cell interaction, cell-microbe interactions, and immune response. The core fucose residues on the N-glycans attached to IgG and IgE antibodies regulate the antibody activities. The 1,2,3,4-Di-O-isopropylidene-alpha-D-fucopyranose is designed as an inhibitor of fucosylation and glycan binding proteins.

Physical and Chemical Properties

1,2,3,4-Di-O-isopropylidene-alpha-D-fucopyranose is a white crystalline solid with a melting point of 83-85 °C and a density of 1.108 g/cm3. It has a solubility of 137 mg/mL in methanol at 20 ˚C and a pKa of around 12.6. Infrared spectroscopy and proton nuclear magnetic resonance indicate the presence of isopropylidene, fucose, and tert-butyl groups in the structure.

Synthesis and Characterization

The synthetic route used for the synthesis of 1,2,3,4-Di-O-isopropylidene-alpha-D-fucopyranose is a multi-step process. The starting material is fucose, which undergoes acetalization with acetone using an acidic catalyst to give 1,2-O-isopropylidene-alpha-D-fucopyranose. The di-protected fucose is then deprotonated in presence of tert-butoxide ion, followed by the addition of tert- butyl bromoacetate to form a di-tert-butylated fucopyranose. Further deprotection with aqueous acid gives the desired product. The product is characterized using NMR spectroscopy, mass spectrometry, and X-ray crystallography.

Analytical Methods

Several analytical methods are used to detect and measure the levels of 1,2,3,4-Di-O-isopropylidene-alpha-D-fucopyranose, including HPLC, NMR spectroscopy, and mass spectrometry. High-performance liquid chromatography (HPLC) is the most widely used method that allows quantification of Di-tert-butyl fucose in biological samples.

Biological Properties

1,2,3,4-Di-O-isopropylidene-alpha-D-fucopyranose serves as an inhibitor of fucosylation, especially in the golgi where the complex glycosylation processes occur. It does this by inhibiting the fucosyltransferase that adds fucose to the glycan chains. The inhibition of fucosylation has been shown to affect cell migration, proliferation, and recognition by certain lectins.

Toxicity and Safety in Scientific Experiments

Studies on the toxicity of 1,2,3,4-Di-O-isopropylidene-alpha-D-fucopyranose are limited. However, it is important to note that the compound can only be used in vitro as it is not metabolized in the body and can hinder proper glycosylation. Doses higher than required for the inhibition of fucosylation may lead to both loss of function and cytotoxicity and should, therefore, be avoided.

Applications in Scientific Experiments

1,2,3,4-Di-O-isopropylidene-alpha-D-fucopyranose is used extensively in research related to glycosylation and lectin studies. It is used to compare the activity of complex-specific fucosylation enzymes and for the inhibition of specific glycan receptors. For example, the inhibition of core fucosylation of Fc isotypes using 1,2,3,4-Di-O-isopropylidene-alpha-D-fucopyranose has been shown to improve the antibody-dependent cellular cytotoxicity function of monoclonal antibodies, leading to better clinical outcomes.

Current State of Research

Currently, research is ongoing on the application of 1,2,3,4-Di-O-isopropylidene-alpha-D-fucopyranose in cancer research. It has been suggested that inhibiting fucosylation as a therapeutic strategy could lead to anti-tumor effects. Using 1,2,3,4-Di-O-isopropylidene-alpha-D-fucopyranose as a tool to inhibit fucosylation, research has shown that it sensitizes cancer cells to chemotherapy and immune cell-mediated killing.

Potential Implications in Various Fields of Research and Industry

The potential implications of 1,2,3,4-Di-O-isopropylidene-alpha-D-fucopyranose in various fields of research are immense. The use of 1,2,3,4-Di-O-isopropylidene-alpha-D-fucopyranose can help in developing more potent antibodies and other biotherapeutics with improved functional activity. Moreover, the inhibition of fucosylation could be used as a therapeutic strategy in cancer treatment.

Limitations and Future Directions

One of the limitations of 1,2,3,4-Di-O-isopropylidene-alpha-D-fucopyranose is its non-biodegradability and thus, it has to be used with precision and under controlled conditions. Another limitation is the limited research on its toxicity and safety.

Future directions for research on 1,2,3,4-Di-O-isopropylidene-alpha-D-fucopyranose include:

- Developing more potent and specific inhibitors of fucosylation.

- Investigating the effects of fucosylation inhibition on other biological processes.

- Studying the relationship between fucosylation and inflammation.

- The use of 1,2,3,4-Di-O-isopropylidene-alpha-D-fucopyranose as drug delivery vehicles targeting specific glycan receptors.

- Development of more efficient forms of glycan synthesis.

In conclusion, 1,2,3,4-Di-O-isopropylidene-alpha-D-fucopyranose is an essential compound in the field of glycosylation research that is useful as an inhibitor of fucosylation and glycan receptors. It shows great potential for the development of more efficient biotherapeutics and as a therapeutic strategy in cancer treatment. Further research is necessary to fully elucidate the potential applications and limitations of 1,2,3,4-Di-O-isopropylidene-alpha-D-fucopyranose.