Project Overview
Purpose
Type II Diabetes affects 29.1 million people and it is projected that 84.1 million people will be affected in the coming years. Current treatment consists of the prescription drug, metformin. However, metformin is known to cause a serious side effect known as lactic acidosis which can be fatal if left untreated. An emerging treatment for Type II Diabetes are glucose-derived spiro-isoxazolines or GDSI.
Type I Diabetes is another disease that effects the lives of many people around the world. While there is no "cure" for this branch of Diabetes, it can be inhibited. This can be done through the use of a medication known as ISO-1.
​
Both of the aforementioned medications (ISO-1 and GDSI) are synthesized from a precursor known as 3,5-disubstituted Δ2-isoxazoline. My research focuses on synthesizing 3,5-disubstituted Δ2-isoxazoline in a less expensive method with an overall goal to eventually to lower the overall costs of ISO-1 and GDSI.
​
Background
As previously mentioned, Type II Diabetes can be treated by glucose-derived spiro-isoxazolines (GDSI). This drug works by targeting and inhibiting glycogen phosphorylase which is an enzyme that depolymerizes glycogen into glucose. When this enzyme is inhibited by the drug, it will create glucose at slower rates, thereby reducing the blood sugar concentration. When the glucose levels are lowered in the blood stream, Type II Diabetes symptoms will be effectively mitigated.
​
​
ISO-1 is a medication that can be used to treat Type 1 Diabetes. In Type 1 Diabetes, Macrophage Migration Inhibitory Factor (MIF) is a protein that falsely tells the immune system to destroy beta cells in the pancreas. Beta cells produce insulin which is a hormone that is crucial in regulating glucose levels. When these cells are destroyed, there will be no insulin to lower the glucose levels in the body. ISO-1 works by inhibiting MIF which will then protect the beta cells and allow them to produce insulin.
​
3,5-disubstituted Δ2-isoxazoline is a compound that is an important precursor to both ISO-1 and GDSI. However, current synthesis methods rely on the usage of Palladium (II) Chloride which acts as a metal-mediator in the final cyclization reaction. Palladium (II) Chloride is an extremely expensive compound that will then raise the overall costs of the final forms of Diabetes medications. My research focuses on experimenting with different metals in the cyclization reaction in order to decrease the cost of 3,5-disubstituted Δ2-isoxazoline. Essentially, this will then allow for the cheaper production of both GDSI and ISO-1.