| ARTHER GATES: Synthesis of Prostacyclin Analogs |
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| Objective: Synthesize Precursor Molecules Used for Creating Prostacyclin Analogs | |
| Lab: Dr. James M. Takacs | |
| ARTHER GATES: Synthesis of Prostacyclin Analogs |
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| Objective: Synthesize Precursor Molecules Used for Creating Prostacyclin Analogs | |
| Lab: Dr. James M. Takacs | |
| RESEARCH RATIONALE | Prostacyclin and it's analogs are chemicals which have been used to treat Primary Pulmonary Hypertension. The analogs differ by their potential reactivity and stability in the body. Synthesizing molecules which are modifications allows researchers to optimize the chemical effects of the compounds. Arther is primarily focused on creating precursor molecules for the prostacyclins that are synthesized in Dr. Takacs Lab. |
| RESEARCH BACKGROUND | Prostacyclin belongs to a much larger group of fatty acid molecules called eicosanoids (20 carbon fatty acid), which include the prostaglandins, leukotrienes and thromboxanes. This family of molecules are very common in the body, in fact, they have been isolated from almost every tissue and body fluid. |
| Prostacyclins are being explored for their chemical properties in the body. They have been associated with being vasodilators (increase the diameter of arteries) and inhibitors of human platelet aggregation (blood clotting). Patients who suffer from Primary Pulmonary Hypertension or who are highly susceptible to blood clotting may use these compounds in their treatment regime. | |
| Dr. Takac's lab is working on the synthesis of prostacyclin analogs and precursors by focusing on the cyclization of alkenes (double bonded carbon compounds) by using iron substrates, Iron-Mediated Cyclization. | |
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RESEARCH PROCEDURES |
The research Arther is conducting includes six reactions which leads to intermediates of prostacyclin analog synthesis. The procedures and techniques used vary from reaction to reaction, but the focus on optimizing product by varying the practice allows Arther an opportunity to test his skills. | |
| Synthesis |
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| Arther is working on one reaction by heating his substrates and then collecting the volatile solvents using a condenser and collection vile. The clear tubes are water supply lines which cool the evaporated solvents which causes them to condense in the vile on the far right. The reactions are very sensitive to air and water and therefore must be run under a nitrogen atmosphere. A line containing nitrogen gas is connected to Arther's set-up which eliminates air from contacting his substrates | ||
| Isolation |
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The products from his reactions have to be isolated from unreacted substrates and other unwanted products. Arther runs a thin layer chromatography on his product to first determine the different gradients and identify which band is his product. |
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| Isolation of the product is done by a silica gel chromatography column. The silica he is using is called flash silica, which contains very fine particles of sand where the products exhibit varying degrees of affinity binding. Those substances that do not bind very well will flow through first with the higher affinity particles migrating much slower. The column on the right shows the colored banding associated with different substances from the mobile phase of the column. | ||
| Analysis |
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| The products that Arther isolates have to be analyzed for composition and purity. Physical properties such as color and crystal formation are indicators that can help identify his product. NMR spectroscopy is also used as a way to verify his product based on the chemical structure. | ||
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| Celia (Ces) Kingsbury is helping Arther set his sample for taking an NMR reading. | Here is an NMR that Arther ran which helps verify the structure for one of his products. | |
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