Development of Plant Natural Products having Antidiabetic Potential and Antihypertensive Therapy and Chronic Diseases
Daija Bullock-Marable Mentor: Sameh Abdelwahed Chemistry Department Introduction: Since the medieval ages, herbs were used for the treatment of different diseases. Since then, the use of herbs has given rise to the treatment of various modern diseases as well. Due to that fact, most of the modern FDA-approved drugs can be sourced back to plants. Hibiscus sabdariffa and Ginger are used as common for the management of high blood pressure, fever, and other diseases like diabetes1. Our research is focusing on the synthesis of Gingerol, the bioactive compound that’s found in ginger, by using a simple and efficient synthetic route starting from commercially available vanillin. Gingerol could be used also as an antibiotic agent, which encourages us to synthesize this compound in our lab. Based on our computational study, our hypothesis is that Gingerol could be used as a drug for antidiabetic and antihypertensive properties. Previous studies have shown that some medications for diabetes cause high blood pressure and lower blood sugar, which is not good for someone suffering from a lack of insulin. Several exciting advances in the understanding of pain relief have recently been published that relate to this class of compounds. Our study is worthy of investigation because gingerol is natural and has so many beneficial effects to aid in diabetes. Gingerol is one of the medicinally active components of the ginger root is from the class of compounds called vanilloids. Methodology: Vanillin (1mmol) and acetone (4mmol) in a beaker (100ml) containing 15 ml of 10 percent aqueous sodium hydroxide solution. The beaker containing the mixture was covered with a watch glass and stirred for 2 hours and 15 minutes. Did a neutralization procedure to separate the water layer from the product. Flited, washed and crystallized from ethyl acetate.
Me O HO
O H
Me O
O
+
Base
Me O HO
O
HO
O
Me O Reduction
Me O
OH
6-Gingerol
HO
Hydrolysis
O
Witting Reaction O
O
HO
Use of Tetrahydrofuran, n-butyllithium, and Lithium diisopropyl amide. Flame dry a flask, then added 1.0 equivalent of zingerone and dry THF. The solution was cooled to zero degrees, and 1.0 equivalent of n-BuLi in hexane was added. The resulting mixture was stirred for half an hour at zero degrees. Then LDA was added dropwise, which was prepared from one equivalent diisopropyl and one equivalent of n-BuLi in THF at zero degrees. The reaction was stirred at low temperature for 3 hours, then 1.0 equivalent of the appropriate aldehyde, hexanal in THF at zero degrees was added. After stirring for 3 hours at zero degrees, the reaction was quenched with methanol. The crude oil was chromatographed (added EtOAc) to yield pure gingerol The second gingerol method to a stirred solution of Zingerone (3.1941 mg, 10 mmol) and tBuOK (2805 mg, 25 mmol) in THF (100 mL) was added hexanal (1.48 mL, 12 mmol) at 78 C (zero degrees). After 1.5 h, the reaction was quenched by the addition of saturated aqueous NH4Cl(ammonium chloride). The mixture was extracted with ethyl acetate. The combined organic layer was washed with brine, dried over MgSO4 (magnesium sulfate), filtered, and evaporated to dryness under reduced pressure. The crude product was purified by flash column chromatography. Took gingerol form 3 weeks of stirring and work up the reaction, and tested the tlc. Used solution of 4-acetyalminobenzesulfonyl chloride 2.34grams, in 20 ml of methanol, added S=thiomorphline 2.00 ml (in room temperature). Let reflux for 3 ½ hours (suppose to be 4 hours). Precipitation formed while mixing. Took out from heat Page 139 and water but let it stir for 4 days room temp (30 minutes in room temp). Vacuum filtered, washed with of 3cold distilled water,
