Daija Bullock-Marable

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.

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 and water but let it stir for 4 days room temp (30 minutes in room temp). Vacuum filtered, washed with cold distilled water,

Me O O H

HO + O

Base Me O

HO

Me O

HO O OH

6-Gingerol O

Reduction Me O

HO

Hydrolysis Me O

HO O

Witting Reaction

O

O

and waited till completely dry. Added 50% ethanol under heat to crystalize by compound (dissolve in the smallest amount of solvent, place under heat, Scratch to make crystals form faster). Analysis and findings: Through the nmr of the zingerone or 4,(4 hydroxyphenyl 3-methoxy) 3-butane 2-one shows that there is a trace amount of the starting material and an equal amount of a new compound, which is our zigerone. So, this compound

will have to be purified again, As shown in the top nmr, it shows the peaks for vanillin. In the zingerone nmr below it is evident that the staring material in there as stated in the previous slide.

In the nmr for the thiomorpholine, there is a large amount of starting material shown in peaks on 5.0 and not much of a new compound 4.0-2.0 Conclusion: Gingerol is a multifaceted natural or synthetic-based compound that could be used as a drug for antidiabetic and antihypertensive properties. Throughout our research, we have found this to be a drug that is effective in the studies of diabetic medicines. Upon completion of the gingerols, which were found using two different methods, we found that our compound wasn’t pure enough; it still contained fairly high amounts of the starting material. So, the process will have to be done over. When done, we will seek collaboration to test the effects of gingerol as an antidiabetic agent.

References:

Monika Gupa “A simple and efficient method for selective single aldol condensation between aryladehydes and acetone” Synthetic communication, vol. 35:213-222, 2005, University of Jammu, Jammu India Chemistry dept. Nafiseh Khandouzia , Farzad Shidfarb*, Asadollah Rajabc , Tayebeh Rahidehd , Payam Hosseinie, and Mohsen Mir Taheri “The Effects of Ginger on Fasting Blood Sugar, Hemoglobin A1c, Apolipoprotein B, Apolipoprotein A-I and Malondialdehyde in Type 2 Diabetic Patients” Iranian Journal of Pharmaceutical Research (2015), 14 (1): 131-140 Satya Paul, and Monika Gupa “A simple and efficient method for selective single aldol condensation between aryladehydes and acetone” Synthetic communication, vol. 35:213-222, 2005, University of Jammu, Jammu India Chemistry dept.