Truc Nguyen Dr. Whitesell Chem 151 14 March 2014

The Queen of Fruits

Ever since I was a child, my mother would always make tea infused with mangosteen for me to drink. I always reached for the mug of hot tea with a sigh of happiness as I inhaled the fruity scent of mangosteen through my tiny nose. After every mug of tea, my mother would say, “Drink this every day even when I am not around for mangosteen is the ‘queen of fruits.’” I would always crinkle my nose and giggle at the thought that one fruit could be the queen of anything and did not think much of it. As I grew up and moved out of the house, I continue to drink mangosteen tea. Even after many years of my mother talking about mangosteen, I never was curious about mangosteen’s benefits until one day I decided to research mangosteen and discovered a compound in the fruit that changed the health of millions of people around the world.

What gives mangosteen its unique nickname as the “Queen of Fruits”? Mangosteen is

rich in xanthones that fight free-radicals in our cells. The mangosteen super fruit (Garcinia Mangostana) is primarily found in several tropical plants in Southeast Asian countries, such as the Philippines, Indonesia, and Malaysia. Garcinia Mangostana was named after Laurent Garcin, a French explorer, during the 18th century. In 1903, David Fairchild, an American botanist, referred to mangosteen as the “queen of fruit” because he thought highly of the mangosteen fruit. Once the mangosteen tree is planted, it may take up to 10 years for the tree to bear fruit. The mangosteen tree produces fruit only twice in a year2.

Xanthones are well known for their antioxidant properties. Several liquid nutrition companies, such as Vemma, used mangosteen as the main ingredient in promoting health and made $240 million sales in 20137. Many people recognize the benefits of drinking mangosteen juice but it is the xanthones are working hard to combat free radicals. The characteristic yellow color of xanthone is derived from the Greek word “xanthos” for “yellow.” Xanthone, a heterocyclic organic compound, is found in the pericarp, or the rind, of the mangosteen fruit. The pericarp has a bitter taste, but the behavior of xanthones at a high temperature describes the importance of these molecules in the body. The chemical and physical properties of xanthones make them prime examples of heat stable compounds with powerful antioxidant features. The mangosteen fruit10, or the pulp, contains essential minerals and vitamins, such as calcium and Vitamin C, respectively8. The pericarp, or the rind, is a major and natural source of xanthones. Figure 1. Components of Mangosteen. Mangosteen has two components, the fruit and the pericarp. The pericarp is rich in the antioxidant xanthone molecule.

There are over 120 classifications of xanthones and out of the 120 different xanthones, approximately 40 types are in the mangosteen fruit which is more than the amount of xanthones in any plant. Xanthones share a common backbone, but the functional side chains give rise to

unique xanthone derivatives, which are key components in polyester production in textiles3. Among the plethora of xanthones found in mangosteen, a few essential xanthones include α-mangostin, β-mangostin, ϒ-mangostin, gartanin, mangostanol, and garcinone A through E. Mangostin, a compound in mangosteen, was classified as a xanthone in the mid-1800s1,5.

Xanthones are useful in combating cancer, but each xanthone has its own special function. For example, α-mangostin helps suppress tumor cells that cause cancer while garcinone E targets cancer cells in the lungs, liver, and gastrointestinal (G.I.) tract. ϒ-mangostin is effective in inhibiting the cyclooxygenase (COX) 2 enzyme which induces inflammation, a major cause in arthritis and other diseases such as Alzheimer’s, cancer, and Parkinson’s. Inhibition by the xanthone ϒ-mangostin allows it to decelerate the natural production of the COX 2 enzyme in the body. Garcinone B, α-mangostin, and β-mangostin are capable of inhibiting tuberculosis9. Xanthones are anti-inflammatories that can suppress aging, bacteria, viruses, and tumors by slowing down cell proliferation. Detection of Xanthones

The identification of xanthones involves using fluorescence markers or dyes to label the compounds and a fluorescent spectrometer for analysis. There are other methods to detect these organic compounds, such as absorption, but fluorescent spectroscopy has greater sensitivity and thus can help provide a more efficient way to detect the xanthones. Figure 2. Fluorescence of Xanthones. An incoming photon (hυ) of energy bombards and excites the xanthone compound via intersystem crossing (ISC)4. The photo-excited state 1ππ* is lower in energy than the triplet excited state 3nπ*.

Upon the absorption of a photon, the electrons transition from the ground to the excited state. The emission of the photon, or non-radiative vibrational relaxation, leads to fluorescence. The fluorescence quantum yield of xanthone in water is 100 fold larger than in other solvents, which is around 10-4. Both processes yield an ultrafast time of 1 picoseconds4. The quantum yield determines the efficiency of fluorescent processes; quantum yield is equal to the number of photons emitted over the number of photons absorbed. A high fluorescent quantum yield results in a high fluorescent sensitivity. Structure of Xanthones

Molecular structures are crucial in understanding the interaction of individual atoms in a molecule or compound. The determination of a chemical structure utilizes techniques such as x-ray crystallography, NMR, IR, and electron microscopy.

Figure 3. Ball-and-Stick Model of Xanthone9. Xanthone is an organic compound and a powerful antioxidant. The stick represents the bond between two atoms and the ball represents the atom; black is carbon, red is oxygen, and white is hydrogen.

Xanthone contains conjugated aromatic rings, several double carbon bonds, and an aromatic ketone at carbon 9. The carbon and oxygen atoms give rise to its heterocyclic properties. The carbon-oxygen bond of the carbonyl group is polarized because the oxygen atom, which is more electronegative than carbon, pulls the electrons towards itself

and thus, results in a higher electron density and a more electronegative charge. The electrons are moving away from the carbon atom, giving carbon a more positive charge. The polar vector points toward the direction of the more electronegative atom, which in this case is the oxygen atom. Synthesis of Xanthones

Xanthones were first synthesized in 1939 by heating phenyl salicylate but another method was to oxidize xanthene in presence of chromic acid5. Phenyl salicylate is an important precursor in the production of xanthone. Thus, the question is, how is it synthesized? Phenyl salicylate is produced by reacting salicylic acid and phenol in the presence of an acid catalyst and heat.

Figure 4. Chemical Synthesis of Xanthone from Phenyl Salicylate6. Phenyl salicylate forms xanthone using acid catalyst (H+) and heat.

The synthesis of phenyl salicylate involves reacting salicylic acid with phenol. The reaction of a carboxylic acid and an alcohol leads to the formation of an ester. The oxygen atom of the carbonyl group becomes slightly negative and acts as the nucleophile, which attacks the proton. Then the oxygen atom of the alcohol attacks the electrophilic carbon in the carbonyl group. The oxygen of the alcohol undergoes deprotonation with the addition of a base. The hydroxyl group becomes a good leaving group via protonation. Pushing an electron pair from the oxygen atom forms a double bond with the carbonyl carbon and gives the oxygen a more positive charge. The release of a water molecule results from pushing electrons. In solution, the oxygen atom of a water molecule attacks the hydrogen and releases an oxonium ion H3O+. Since the water molecule removes the hydrogen atom, the electrophilic oxygen atom of the carbonyl group pulls the electron pair towards itself and thus eliminates the positive charge of the oxygen. In the presence of an acid catalyst and the addition of heat, salicylic acid and phenol undergoes Fischer esterification to produce phenyl salicylate which is used to synthesize xanthones.

The Vemma Solution: Elimination of Free Radicals The xanthones in mangosteen are powerful antioxidants, anti-inflammatories, and

contain multiple health benefits such as eliminating and preventing free radicals from coming into contact with harmful enzymes in the body. Since ketones lack a hydrogen atom on the carbonyl group, ketones will not undergo oxidation and therefore is the reason why xanthone is a potent antioxidant and contains medicinal and nutritional properties. Xanthones can help lower LDL (low-density lipoprotein) cholesterol, also known as the harmful type of cholesterol. How do xanthones do this? By blocking contact between free radicals and LDL cholesterol, oxidation cannot occur and thus it prevents LDL cholesterol from clinging to the arteries, which can lead to blood clots and heart diseases, such as atherosclerosis.

In addition, xanthones can inhibit oxidative processes in the body by accepting or donating electrons to trap reactive oxygen species, such oxygen free radicals and hydrogen peroxide, or other radicals, such as hydroxyl and lipid radicals. An abundance of molecular oxygen can generate oxygen free radicals, which are unstable oxygen molecules and lipid radicals can result in lipid peroxidation. These oxidative processes will cause DNA degradation, cellular damage and dysfunction. Xanthones cannot cure cancer, but they can suppress tumor production, which leads to cancer. A clinically studied formula from Vemma, a company specializing in healthy energy and liquid nutrition, and vitamins, essential minerals, aloe vera, and xanthone-rich mangosteen juice all serve as antioxidants and nutrients to help fight cancer, neutralize free radicals, and enhancing the body’s defense and overall health. References

1. American Cancer Society. “Mangosteen Juice.” 1 Nov. 2008. Web. 1 Mar. 2014. 2. Dohn. “The Mangosteen: Queen of All Fruits.” Hub Pages, Inc. 2014. Web. 1

Mar. 2014. 3. eHow. “What is Xanthone?” Web. 18 Jan. 2014. 4. Heinz, B, et al. “On the Unusual Fluorescence Properties of Xanthones in Water.”

Physical Chemistry Chemical Physics. Journal. 15 Feb. 2014. 5. Maui Farmers United Union. “Adding Value to Locally Grown Crops.” Web. 7

Feb. 2014. 6. Organic Syntheses. Xanthones. Web. 1 Feb. 2014. 7. Vemma. “Vemma Nutrition Company Doubles Sales in One Year.” BevNet. 8

Aug. 2013. Web. 1 Mar. 2014. 8. VemmaNews. “Mangosteen 101: Part Three.” 12 Jun. 2012. Web. 18 Jan. 2014. 9. VemmaSolution. All About Xanthones. Web. 18 Jan. 2014. 10. Wikipedia. Xanthones. Web. 18 Jan. 2014.