Organic Chemistry in Nature

Spring 2001 

Chemistry 312 - Organic Chemistry II 
at Virginia Wesleyan College

Research Essay Project

The natural source of the organic compound is described, as well as the primary uses for the compound.  A brief explanation of its purification from its natural source and/or its laboratory synthesis is included.  Resources are listed below the compound's information.  The structures were made using the ChemSketch program from ACD Lab Software.  

Ascorbic Acid - Kevin Cartwright

Ascorbic acid or vitamin C (L-3-ketothreohexuronic acid lactone) is essential to our lives.  It has the chemical formula C₆H₈O₆ and a molecular weight of 176.12g/mol.  The hydroxyl groups and the other oxygen atoms give it a melting point of 190-192°C.  They also allow it to be acidic and soluble in water and other polar solvents.  Vitamin C is used as a coenzyme in the production of collagen.  It is also thought to be a helpful tool to the immune system also.  

Ascorbic acid was first isolated from citrus fruits in 1932, but it had been known about since James Lind found that citrus fruits prevent scurvy in the 1700s.  There are two pathways for the synthesis for ascorbic acid.  They both begin with D-glucose.  One is the inversion pathway and uses the L-Galactono-1, 4- lactone dehydrogenase. The second pathway is the non-inversion pathway and uses the enzyme sorbosone dehydrogenase.

Benzaldehyde - Kim Campbell

Benzaldehyde is the simplest representative of the aromatic aldehydes.  It is found in cherries, almonds, apricot and peach pits.  It is found in nature as the glycoside amygdalin, which is a sugar derivative of the cyanohydrin of benzaldehyde that is found in bitter almonds.  It was first isolated in 1803.  Benzaldehyde is best known as being artificial essential oil of almond but it has many other uses such as; the manufacturing of dyes perfumes, flavorings, cinnamic and mandelic acids, and it is also used as a solvent.  It is synthesized in laboratories from toluene being chlorinated to benzyl chloride or by direct oxidation of toluene with manganese dioxide.  Some more recent developments in the use of benzaldehyde are for the health and agriculture industries.  Benzaldehyde is being used as a pesticide and also as an anticancer agent. These uses are still in development but would be very  helpful in solving some of these problems of today.

Caffeine - Lisa Fusco

Caffeine is a white, crystalline powder with a bitter taste that can be found naturally in many different plants.  For thousands of years natives of Asia, South America and Africa have used these plants, because they contained caffeine.  In Africa, upper class tribal members would chew Kola nuts and coffee beans because the affects would increase their energy for long hunts and hindered the pain of weary bodies.  In South America, the coca plant and coffee beans were chewed upon because the caffeine would stop hunger pains and for the natives of the mountain regions, they ate these caffeine enriched plants to raise their heart beat and thus their body temperature.  In Asia, tea was a favorite of the people because it was said to sharpen their mental skills and prolong attention in challenging subjects.
Caffeine is still used to do all these things.  It is known as the perfect "stay awake" drug and is also used by doctors to accompany perscriptions, such as antihistamines and painkillers that can make the patient drowsy. It targets the central nervous system by stimulating the body in all the ways that natives from South America, Africa and Asia believed they did.  However, when too much is taken, insomnia, irritation, headaches and anger can result.  
Caffeine is addictive and can be found in most sodas, tea, chocolate, coffee and cocoa.  Caffeine is added to most of these products in the powdered form after it is extracted from tea, or coffee.  It is removed by first boiling it in water, in which it is highly soluble.  Then, after a concentrated mixture is created, the tanins of the tea or coffee (the colored components) are separated from the caffeine by doing three extractions with dichloromethane,  in which it is even more soluble. The crude product is dried and then sublimed to complete the purification.  The caffeine crystals are then collected and can be put in a pill form or mixed into a soft drink.

Williamson, Kenneth L. "Macroscale and Microcale Organic Experiments";Houghton Mifflin Company: Boston,1999;third edition,146-150.

Calanolide A - Troy Shell

Calanolide A was found in the extract of Calophyllum lanigerum var. austrocoriaceum, which exists in the Malaysian rainforests (2).  The National Cancer Institute found Calanolide A to be remarkably effective against HIV-1, the most common strain of the AIDS virus in the Western world (3).  Today, Calanolide A is in the developmental drug phase and is a member of the HIV drug class of non-nucleoside reverse transcriptase inhibitors (4).  Calanolide A blocks transcription of the viral RNA into DNA within the host cell’s cytoplasm, therefore preventing replication of the HIV virus (5).  The synthesis of Calanolide A begins with a triphenol (6).  There are four ring-building reactions, one of which is a Friedel-Crafts acylation, followed by a reduction from a ketone to an alcohol in the fifth and final reaction of the synthesis (6).  Unlike many HIV drugs, Calanolide A produces mainly mild and temporary side effects (4).  For the most up-to-date information on the development of Calanolide A as an HIV drug, go to http://www.sarawak-medichem.com.

(1)     Sarawak Medichem Pharmaceuticals, Inc.  ‘Sarawak Medichem Pharmaceuticals Home Page’ http://www.sarawak-medichem.com (April 9, 2001)
(2)     Diamond, N.  “Tropical delight, disaster, and discovery: finding cures among the wreckage of a hurricane” Omni 1994, 16 (8), 22. 
(3)     Shenon, P.  “Hunt in forests of Borneo aims to track down natural drugs” New York Times (Late New York Edition) 1994, December 6, C4. 
(4)     Sarawak Medichem Pharmaceuticals, Inc.  ‘The Unique Features of Calanolide A’ http://www.sarawak-medichem.com/cala/calafeat.htm (April 9, 2001)
 (5)     AIDSDRUGS Database.  ‘DRG-0308’  http://www.actis.org/rwscripts/rwisapi.dll/@actis.env?CQ_SESSION_KEY=TWRCAAMWDRXM&CQ_CUR_DOCUMENT=1&CQBASE=AIDSDRUG&CQINNER=CQ_RECORD=Yes (April 9, 2001)  
(6)     Chenera, B., M. West, J. Finkelstein & G. Dreyer.  “Total synthesis of (±)-Calanolide A, a non-nucleoside inhibitor of HIV-1 reverse transcriptase” Journal of Organic Chemistry 1993, 58, 5605-5606.

Dopamine - Stephanie Dodgers

Dopamine is an important neurotransmitter located in the substancia nigra part of the brain.  Dopamine has a molecular formula of C₈H₁₁NO₂ and a molecular weight of 153.18 g/mol.  Dopamine is a member of the catacholamine family, which has a characteristic benzene ring with hydroxyl groups in the third and fourth positions.  Alterations of the dopamine content in the brain are responsible for many severe neurological disorders such as schizophrenia, Parkinson’s disease, and Tourette’s syndrome.  Dopamine was first recognized as a neurotransmitter in the late1950’s.  In the following years, much research was done by Carlsson, Kandel, and Greengard linking dopamine to the mentioned disorders as well as pinpointing dopamine’s exact function.  The scientists won the Nobel Prize in physiology or medicine in 2000 for their research.  Dopamine can be purified from dopamine neurons and nervous tissue.  This isolation and purification has been performed in laboratory rats, bovine, and humans.  Dopamine is synthesized in vivo through several enzyme-catalyzed reactions beginning with the amino acid tyrosine.  However, in the laboratory, dopamine is made from an enzyme-catalyzed reaction between L-Serine and Pyrocatechol.  The discovery and understanding of dopamine has been extremely beneficial to society in furthering our understanding of the brain and neurological disorders. 

1)  Nash, J. Madeline "Not So Dopey Dopamine" http://www.time.com/time/magazine/printout/0,8816,57762,00.html, April 11, 2001.
2)  "Dopamine" http://neuroscience.about.com/science/neuroscience/library/g/d/bl-dopamine.htm,  April 11, 2001.

Ethanol - Craig O'Neill

          Ethanol
       Ethyl Alcohol
Ethanol has been used for centuries.  There is no exact record of its discovery.  However, it is known to have been used by the Arabs and monks in the early 1200’s.  Ethanol is a simple compound, C₂H₆O.   
Ethanol has many names, which range from ethyl alcohol, absolute alcohol, anhydrol to ethyl hydrate.  The molecular weight is 46.088 g/mol and the density is 0.789 g/mL.  Ethanol has an extremely low melting point, -114.1^oC.  The boiling point is 78.3^oC, because ethanol is capable of hydrogen bonding with itself.  Ethanol is used as solvent, extraction medium, antiseptic,sedative, and an alcoholic beverage, as well as a component or in the manufacture of perfumes (because of its ability to evaporate quickly), pharmaceuticals, lacquers, plastics, cosmetics, rubber, mouthwash, aerosols, antifreeze, and dehydrating agents.  Ethanol can be synthesized using ethylene.  Ethylene undergoes an acid-catalyzed hydration.  A H⁺ ion is added to the double bond forming a carbon with a positive charge.  The oxygen from a water molecule donates a pair of electrons to this carbon.  The water molecule now has the positive charge.  In order to regain its neutral status, it sheds a hydrogen to form ethanol.  

 1.  Salzberg, Hugh W., From Caveman to Chemist; American Chemical Society, Washington, DC, 1991
 2.  www.chemfinder.com/result.asp, 04/04/01.

Methanol - John Tomasheski

    Methanol 
Methyl alcohol
Pyrolysis, or a technique of applying high heat to organic matter in the absence of air or in reduced air, is an ancient method of producing methanol.  Ancient Egyptians used pyrolysis, otherwise known as wood distillation, to produce tars and other chemicals used for embalming.  Despite this ancient production of methanol, the simple alcohol was not officially discovered until 1661 by Robert Boyle. 
Within society, methanol serves many purposes.   Currently, methanol is being studied to learn its advantages over gasoline as an automotive fuel.  It is also used as automotive antifreeze because of its low freezing point, as well as rocket fuel and a general solvent for many experiments and compounds.  The modern method for synthesizing methanol involves the direct combination of carbon monoxide gas and hydrogen gas in the presence of a catalyst, ZnO-Cr₂O_3.  The reaction also takes place under high pressure, between 300 – 400 atmospheres, and a high temperature of 300 – 400^oC. In contrast with the impure product obtained by wood distillation, synthetic methanol is a chemically pure material. 

Oxytocin - Devenia White

Oxytocin is a hormone that stimulates uterine contractions and lactation in pregnant females. This hormone is produced naturally by the female in her posterior pituitary gland. This gland is located at the base of the back of the brain. (1) Once the strong uterotonic agent has caused uterine muscle to expel the baby from the mother’s womb, more oxytocin is released when the infant begins to suck on its mother's breast. (2) The release of the oxytocin in the breasts causes myoepithelial cells, which surround the alveoli, in the mammary glands to contract and excrete milk. (2) During labor, this hormone also causes higher blood pressure and less urine formation. (3) Oxytocin is commercially used to induce labor in pregnant females when the unborn child is at risk and the mother has not yet produced this hormone herself.
Between 1909 and 1911 Sir Henry Hallet Dale discovered and extracted oxytocin in and from the pituitary gland. (1,4) Oxytocin was also extracted from gonads, placenta, adrenal glands, uterus, and male accessory glands. (5) Oxytocin’s synthesis goes through multiple steps, essentially it is a peptide synthesis involving a series of condensation reactions forming amide bonds.  Oxytocin is also modified to form the cyclic configuration. This compound was then oxidized by exposure to air. (6) During oxidation, the hydrogens that are attached to the sulfur were released and the two sulfurs reacted to form a disulfide bond. The final product of this lengthy synthesis was C₄₃H₆₆N₁₂O₁₂S₂, better known as oxytocin.

1  Cushing, Harvey,  “The Role of the Pituitary Gland” http://www.medivisionindia.com/eureka/1912.phtml, 04 –09-01.
2  Dreifuss, J.J., “Oxytocin in Reproductive Biology: Newly Discovered Sites of Production and of Action” http://matweb.hcuge.ch/matweb/ endo/Reproductive_health/ Oxytocin_ in_ reproductive biology.html, 04-09-01.
3  Williams, “Endocrine Glands” http://www.geocities.com/Athens/Parthenon/6853/glands.html, 04-09-01.
4  “Dale, Sir Henry Hallett”  http://www.fwkc.com/encyclopedia/low/ articles/ d/ d006001634f.html, 04-09-01.
5  “ Reproductive Hormones” http://www.uwyo.edu/ag/anisci/wjm/repro/rephorm.htm,    04-09-01.
6  Du Vigneaud et al., “The Synthesis of Oxytocin” Journal of the American Chemical Society 1954, vol. 76 no. 9, pp 3115-3121.

Pyridoxal Phosphate - Courtney Cornwell

Pyridoxal phosphate, or vitamin B6, plays an important role in many functions of the body.  It maintains proper function of nerves and the brain, as well as chemical balances.  It was discovered through nutritional experiments in which lab rats were fed vitamin-deficient diets.  It is a part of many different reactions, such as racemization of stereoisomers to make cell walls in bacteria and transisomerization.  It is a part of the aldehyde family, but because of the nitrogen, it is also an imine.  It absorbs ultraviolet light at 390 nm in alkaline solutions, but only 295 nm in acidic solutions.  It is a water-soluble vitamin, which can lead to major defects in the body if too little or too much of it is present.  Vitamin B6 deficiency can lead to impaired neural functioning that can sometimes be reversed, but only after months or years.

Quinine - Sara Simms

Quinine's systematic name is (8a,9R)-6'-methoxycinchonan-9-ol. It has been primarily used to treat malaria, and even though other synthetic treatments have been produced, it is still used to treat strains that are drug resistant.  Quinine is also used to relieve nighttime leg cramps, although the means by which it does this is still unclear. Quinine was first discovered in South America in the 1600's, when Spanish explorers and missionaries used the bark of the Cinchona tree as medicine. Peruvian Jesuits introduced quinine to Europe in 1640, in the form of a white powder from the bark. Destruction of the cinchona trees, because of the demand for quinine, made them very rare, so a synthesis method of producing quinine from coal tar was discovered by Robert Woodward and William Doering in 1944. Quinine is synthesized by the Mannich Reaction, as ferrocene is converted to dialkylaminomethyl ferrocene by methanol and a dialkylamino (or piperidine). Condensation with formylquinoline produces quinine, which has two chiral centers.

Brocard, J. et al. "US Patent and Trademark Office - United States Patent  6,127,543: Antimalarial organometallic iron complexes"  http://www.uspto.gov/patft/index.html

Succinic Acid - Melissa Downs

Succinic acid, or butanedioic acid, is an organic compound that was originally observed in nature within all plant and animal tissues. It plays a significant role in their intermediary metabolism and the Kreb's Cycle (1).  However, scientists could not come up with a way to purify the succinic acid from the plant and animal tissue in which they observed it.  Then, in the 19th century, German, Swedish, an Swiss chemists recognized that succinic acid was present in amber, a translucent fossil resin (or waste secretion) which comes from trees.  Amber was believed to contain 3-8% succinic acid, which was formed from the micro-organism induced fermentation of the cellulose present in the resin (2).  The succinic acid was then later purified for the first time through the distillation of the amber resin.
Today, succinic acid can also be synthesized in the laboratory.  This can be done in two ways.  The conventional way to do this is to start with n-butane and oxidize it to maleic anhydride.  The maleic anhydride is then hydrated to maleic acid, and the maleic acid is hydrogenated to yield the succinic acid. The second synthesis costs less money and is actually good for our environment.  Not only does this synthesis eliminate a lot of the waste that is produced as byproducts in the conventional synthesis, but it also uses a renewable agricultural starting compound, corn.  Using corn as a starting compound also gives our agricultural industry a new, expanded market in the economy.  To start the synthesis, a microorganism produces succinic acid in high yields by fermenting glucose sugar from the corn.  Next, Advanced Membrane Separation Technology separates and purifies the acid.  At this Point the pure succinic acid can now be turned into chemicals to be used for production of other important products by industries (3).
Succinic acid is primarily used today directly as a flavoring agent for food and beverages. Also, indirectly it can be used as an intermediate for dyes, perfumes, lacquers, and in vehicle water cooling systems and the manufacturing of clothing, paint, inks, and fibers (4).

1-"Britannica.com" http://www.britannica.com/bcom/eb/article/4/0,5716,71944+1+70118,00.html, 4/07/01.
2-"Physical Properties of Amber" http://www.emporia.edu/earthsci/amber/physic.htm, 4/07/01.
3-"Biotechnology at Argonne National Laboratory" http://www.ipd.anl.gov/biotech /programs/chemicals/succinic.html, 4/07/01.
4-"Parchem Trading Ltd.-Succinic Acid-Chemical Pharmaceutical Nutrition Cosmetic Foods" http://www.par-chem.com/products/succinic.html, 4/07/01.

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