Organic Chemistry in Nature

Spring 2003 

Chemistry 312 - Organic Chemistry II 
at Virginia Wesleyan College

Research Essay Project

Ascorbic Acid Guaifenesin Pyrethrin II
Caffeine Isopentyl Acetate Taxol
Galactose Maltol Vanillin
Germanium Norethindrone Vitamin E

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 - Natalia Sepulveda



L-ascorbic acid, commonly referred to as Vitamin C, was discovered in 1912 and isolated in 1933 from lemons.  The compound was first chemically synthesized in 1933 from a carbohydrate precursor via a method called the Reichstein process. This particular chemical synthesis is a mixed fermentation/chemical synthesis, whereby; sorbitol is first oxidized into sorbose by fermentation and then transformed into DAKS (di-acetone-ketogulonic acid) in a two stage chemical process.  In subsequent steps, the DAKS is dissolved in a mix of organic solvents and its structure is rearranged to form Vitamin C, using an acid catalyst.  The crude Vitamin C is then purified by recrystallization. The newer method of chemical synthesis utilized today employs the same first step as the Reichstein process, but in the two stage fermentation process, a second step replaces the chemical reactions used to produce DAKS which results in a different intermediate, KGA.  This newer method makes use of less toxic chemical agents and decreases waste costs.  L-ascorbic acid is biologically synthesized in plants and some mammals through different pathways not clearly understood.  It can be found in many vegetables such as broccoli, bean sprouts, cauliflower and fruits such as oranges, kiwi strawberries (most citrus fruits).  The compound is used today as an antioxidant in the synthesis of collagen and many of its derivatives are used as anti-cancer drugs.  It is an essential vitamin that prevents Scurvy, heart disease, cerebral palsy (and many more diseases) and used in the treatment of AIDS.


“The Natural History of Ascorbic Acid in the Evolution of the Mammals and Primates and Its Significance for Present Day Man” from Orthomolecular Psychiatry,  1972, Volume 1, numbers 2 &3 , pp. 82-89.

 

Caffeine - Cherie Cannady


Caffeine is one of the most popular drugs on the market today. It is a powerful stimulant to the central nervous system (CNS). Millions of people consume the product everyday, probably without even knowing it. It is found in tea, coffee, kola, cocoa, and guarana. The Chinese first discovered the effects of caffeine in the form of medicinal tea about five thousand years ago, for the purpose of staying awake. The active ingredient in coffee and tea was not identified until the nineteenth century (1). It wasn’t until 1820 that caffeine was truly discovered (2). The reason is that the separation of caffeine from a plant is more difficult than just a simple distillation. There are many steps required and the use of a strong solvent (2). There are four processing methods used to remove caffeine from these natural resources: methylene chloride, ethyl acetate, carbon dioxide, and water processing (3,4).  There are many ways to chemically synthesize caffeine in the laboratory. Synthetic caffeine is mainly produced by the chemical synthesis of urea as the basic raw material (5). Caffeine containing plants are used in beverages or herbal materials, more than any other plants. Most people today use it for energy purposes, because it increases mental alertness, which is needed to stay focused (6). Much information has proven that caffeine can actually be a very harmful drug if too much is consumed. It is a mood altering and addictive compound. It can cause nervousness and insomnia (7).

1.  Braun, Stephen. “Buzz: The science and lore of alcohol and caffeine.” New York,  NY. Oxford University Press, 1996.
2.  The World of Caffeine.www.business2.com/images/mag/caffeine.pdf. Bennett Weinberg, A. March 4, 2003.
3.  How Stuff Works.http://home.howstuffworks.com/caffeine1.htm. “How Caffeine Works.” Brain, M. March 5, 2003.
4.  American Chemical Society. http://www.cas.org/portal/vhemistry?PID. “How’d They Do That? Making Decaf Coffee.” Polittle, James. April 4, 2003.
5.  Shri Ahmsa Mines and Minerals LTD. www.naturalcaffeine.com/caffeine. “Natural Caffeine” April 23, 2003.
6.  MEDLINEplus Drug Information.   www.nlm.nih.gov/medlineplus/drugino/uspdi/202105.html#Brands.  March 4, 2003.
7.  Wang, X. “The Psychopharmacology of Herbal Medicine: Plant Drugs that Alter Mind, Brain, and Behavior.” Journal of Natural Products 2002, 65(1), 92-93.

 

Galactose - Kim Mulholland


Galactose is known as a monosaccharide, which is a carbohydrate that cannot be “hydrolyzed to a simpler carbohydrate”.  Galactose is the direct product of the photosynthetic combination of carbon dioxide and water.  Galactose naturally occurs in the body’s brain and nervous tissue, ivy berries and grains, and coffees.  It is used in milk chocolate confectionary products, laxatives, and sports drinks.  However it is more widely used in its combination with glucose to form the disaccharide dairy sugar lactose.  Lactose is crystallized in a laboratory from milk.  The crystals of lactose are collected by suction filtration and washed with small amounts of cold ethanol. In lactose, glucose and galactose are connected by a beta-1,4-glucosidic bond.  The enzyme, beta-galactosidase, otherwise known as lactase, hydrolyzes the beta-1,4-glucosidic bond and breaks down lactose into its two simple sugar components, glucose and galactose.

 

Germanium - Tom Drabczyk


Organic Germanium was discovered in an attempt to synthesize germanium into an organic compound. The idea was to use it for therapeutic reasons. The first compound created was carboxyethylgermanium sesquioxide. Today it is used for multiple treatments of medical conditions, such as arthritis, cancer, leukemia, diabetes, pan, and malaria. Its also used a dietary supplement. In lab this compound is created by a hydrolysis of an organogermanium trichloride.

Reference: http://www.positivehealth.com/permit/Articles/Nutrition/Germanium/chapter1.htm

 

Guaifenesin - Dan Burrell 


Guaifenesin is natural substance that was isolated around the early 1500’s for purported uses to cure rheumatism.  Though it has since been proven ineffective on rheumatism, it is at present, a widely used cough expectorant in nearly every cough, cold, flu, and allergy medication on the market.  The extraction from the natural source is involves a very simple steam distillation process followed by a series of acid-base extractions to remove the guaifenesin resin from the other substituens in the distillate.  As with most natural ingredients, the natural extraction processes are not efficient enough, or the compound simply isn’t abundant enough from its natural sources for a large-scale distribution.  Thus, synthetic processes must be designed to obtain the needed compound.  For the laboratory synthesis of guaifenesin, a simple Williamson ether synthesis reaction will provide the desired product, retaining the stereochemistry of the original stereo reactant, 3-chloro-1,2-propanediol.  The first reactant, o-methoxyphenol, is dissolved in ethanol and refluxed with 6.25M solution of sodium hydroxide, a strong base.  This serves to deprotonate the phenyl ring to give the highly reactive phenoxide ion.  The second reactant, 3-chloro-1,2-propanediol, is also dissolved in ethanol and then added to the reaction mixture after the period of refluxing.  The ethanol is an aprotic solvent that aids in reducing the competing E2 mechanism and is also is a solvent that is easily removed by vacuum filtration.  Washing the precipitated product with water and making several extractions of the aqueous layer serves to remove the formed NaCl and recrystallizing the organic layer from ethyl acetate with hexanes provides the racemically pure product.  Pure guaifenesin appears as a white crystalline powder, that with further analysis is revealed to be minute rhombic prisms.

1. Dicks, A. P.;  Stabile, R. G.  “Semi-Mcroscale Williamson Ether Synthesis and Simultaneous Isolation of an Expectorant from Cough Tablets.”  Journal of Chemical Ecducation.  March 2003.  Vol. 80 No. 3.
2. Jenner, Frank.  “Section I:  Guiaifenesin.”  http://www.cfs-recovery.org/guaifenesin.htm.  March 25, 2003.

 

Isopentyl Acetate  - Stefanie Lake


Isopentyl acetate and isoamyl acetate are the common names for 3-methylbutyl acetate.  This compound was first discovered as one of the alarm pheromones of honeybees (1).  It was later found in and purified from yellow passion fruits, pears, apples, and Zanthoxylum simulans fruits (2).  Isopentyl acetate is sometimes called banana oil, due to its banana-like flavor and smell.  When isopentyl acetate is diluted it has more of a pear-like odor and taste.  It is primarily used as a flavoring agent in various foods and drinks, such as honey, butterscotch, artificial coffee, and alcoholic beverages (3).  Isopentyl acetate is also found in perfumes.  The primary way of synthesizing this ester is through Fischer esterification.  The reactants involved in this reaction are isopentyl alcohol and acetic acid.  Fischer esterification is the nucleophilic addition of isopentyl alcohol to the carbonyl group of the protonated acetic acid.   Nucleophilic addition is followed by elimination of a proton.  An unstable tetrahedral intermediate forms.  This intermediate undergoes dehydration and reforms the carbonyl group.  Reformation of the carbonyl group forms the isopentyl acetate.  Purification of the crude isopentyl acetate is achieved through simple distillation.  Simple distillation is a process used to separate two immiscible liquids (4).

1.  Nunez, Almeida, Balderrama, and Giurfa “Alarm pheromone induces stress analgesia via am opioid system in the honeybee” Physiological Behavior 1997.
2.  Chyau, Mau, and Wu “Characteristics of the Steam-Distilled Oil and Carbon Dioxide Extract of Zanthoxylum simulan Fruits” Journal Agriculture Food Chemical.
3.  “History of Isoamyl Acetate” http://web1.caryacademy.org/chemistry/rushin/st…ate/history.htm.
4.  “The preparation of Isopentyl acetate (Banana Oil)” http://servercc.oakton.edu/~maas/223Labex.html

 

Maltol - John Shannon


Maltol is a compound that was found to occur naturally in Caramel, Chicory, Cocoa, Coffee, Milk, Roasted Malt, Strawberry, and Bread. When added to a broad group of substances, it increases and sustains their sweetness and fragrance (1). Maltol is used to formulate essences for food, cigarette and similar kinds of consumables. It is extensively used in food, beverage, tobacco, brewery, cosmetics and pharmaceuticals industries (2). The smell is often referred to as that of cotton candy and plays an important role in commercial fruit flavoring.  Maltol is synthesized by liquid-liquid extraction.   In the liquid-liquid extraction of maltol, the process is performed between a water-rich liquid phase and a hydrophilic organic solvent-rich liquid phase (3).

 

1.  “Burnt Sugar” http://www.leffingwell.com/burnt.htm March 27, 2003 
2.  “Chemindusty.com” http://www.chemindustry.com/chemicals/search/M/maltol.asp April 22, 2003 
3.  Till Adrian, Jörg Freitag, and Gerd Maurer American Chemical Society 2001 Sept; 4990 -4997http://pubs.acs.org/cgi-bi

 

Norethindrone - Courtney Cornwell




Norethindrone was originally found as a hormone in the human body that suppressd vaginal cornification and estrous cycles during research involving menopausa l women.  It has been used as a progestational oral contraceptive among breast-feeding women because it does not affect breastmilk.  The laboratory synthesis of norethindrone includes esterification of an alcohol followed by oxidation and ethylation.


1. DiNunno, C.M. et al “7alpha-methylnorethindrone enanthate 10beta-hydroperoxide: isolation and characteristics”  Steroids 1983, Volume 42(No. 4), 401-408. 
2. Rao, P.N. “Preparation of 9alpha, 11sigma-tritiated 17alpha-ethynylestradiol, mestranol, estradiol-17 beta, and norethindrone”  Steroids 1971 Volume 18 (No. 2), 219-229.

 

Pyrethrin II - Alena Quigg


Pyrethrin II is an extraction from the Pyrethrum flower.  This flower has been used for thousands of years as an insecticide.  During the 18th century, it became part of a large trade market, leading to an increased desire to discover the identity of the extract’s components.  Directed fractionation led to the discovery of Pyrethrin II’s identity in the mid-1900’s.  See the attached chemsketch document for its structure.  Along with the other components of the Pyrethrum extract, Pyrethrin II is used a safe insecticide because it has a rapid knockdown effect on insects, while maintaining low toxicity toward mammals.  It is also less harmful to the environment than many other insecticides because it has rapid biodegradability.  One might find this compound in fly sprays, household insecticides and grain protectants.  Because Pyrethrin II is unstable in sunlight and air, research has focused more so on the synthesis of stable derivatives of this compound.  The Pyrethrin II involves the synthesis of trans-pyrethric acid followed by the synthesis of a rethrolone (both trans-pyrethric acid and rethrolone are the two key components of the Pyrethrin II molecule), and then both of these are used as reactants to form Pyrethrin II can be seen.

 

 

Taxol - Dawn Bodinski



Taxol has been touted as the most promising anti-tumor agent of the twentieth century.  It was approved for use as a chemsynthetic drug in the fight against ovarian cancer in 1994.  Taxol was first discovered in nature n the Pacific Yew tree.  The problem with using this source is that in order to harvest the taxanes from the bark the tree had to be killed.  The Pacific Yew tree is the slowest growing tree in the world.  To harvest enough taxanes to make enough Taxol for one person with cancer would require the decimation of six two-hundred-year-old trees.   Chemists have been working on a laboratory synthesis of Taxol since the early seventies.  Three groups of chemists, as of 1996, have completely synthesized Taxol in the laboratory.  Each of the groups used a slightly different method to synthesize Taxol many complicated rings.  This synthesis however was very important, not just to the world of chemistry and medicine, but also to the cancer victims, who are now survivors.  The complete synthesis of Taxol can be found in the three journal articles listed below.



1. Nicolau, K.C., et al., Synthesis of Novel Taxoids, 1994, Journal of American Chemical Society, 116, pp. 1591-1592. 
2. Holton, R.A., et al., First Total Synthesis of Taxol. 1. Functionalization of the B Ring, 1994, Journal of American Chemical Society, 116, pp.1597-1598. 
3. Danishefsky, S.J., et al., Total Synthesis of Baccatin III and Taxol, 1996, Journal of American Chemical Society, 118 (12), pp. 2843-2859.

 

Vanillin - Melissa Vindigni




Vanillin can be found in many plants, but is mainly known to be found in Vanilla bean pods.  In today's society, vanillin is used as a food flavoring, in perfumes, as a reagent, and in preserving foods.  Vanillin in synthesized in the lab mainly by first the hydrolysis and second the oxidation of LS (Lignosulfonates) into vanillin.






Vanillin, http://wwwchem.uwimona.edu.jm:1104/lectures/vanilla.html, 3/23/03.

 

Vitamin E - Vanessa Bintliff


Dr. Herbert Evans and Dr. Katharine Scott Bishop discovered vitamin E in 1922, while experimenting on rats. The rats were first fed a diet that lacked vitamin E completely. Those rats became infertile.  After a while, wheat germ oil was added to the rats’ diet and a remarkable thing happened.  The rats became fertile again. The doctors called this new found substance, “food factor X” because it was necessary for the rats’ pregnancy.  A few years later this same oil based substance was isolated in the laboratory and became known as the “antisterility” vitamin.  Then in 1925, the “antisterility” vitamin became known as Vitamin E or alpha-tocopherol. Vitamin E plays a major role in maintaining healthy heart functions, along with healthy nerves and muscles. It can also help build and strengthen capillary walls, and has been shown to help heal wounds without scarring, and lower blood pressure. Since vitamin E encourages collateral circulation in smaller blood vessels, it seems to promote better healing with less scaring.Vitamin E helps to gradually break down blood clots in a person’s circulatory system and also helps prevent more blood clots from forming.
 
Natural vitamin E, alpha- tocopherol, is derived from natural sources since it is synthesized by plants and is found predominantly in plant oils. Leaves of plants also contain high amounts of vitamin E. All seeds, nuts, and grains contain alpha tocopherol. Other sources include wheat germ, soybean, cottonseed, peanut, and eggs. Another major source of vitamin E is in the protective covering of grains. In order for vitamin E to be preserved, extraction of the oils from nuts and seeds must be done naturally by cold pressing.This process is different from the heat extraction or chemical extraction that is commonly used for food processing. A low cost approach to synthesizing vitamin E in a laboratory is from petro-chemicals and turpentine.  Although, this method does pose a synthetic challenge from a methodological viewpoint due to the fact that vitamin E contains saturated and chiral chains.  This synthesizing also helps produce Vitamin E in high yields and high selectivity.  There are esterified forms of vitamin E such as alpha tocopherol acetate, alpha tocopherol succinate, and alpha tocopherol nictoinate.  These forms of vitamin E are synthetic because they made in laboratories.

Hay, Jennifer.  Vitamin E: Everything You Need to Know.  People’s Medical Society: Pennsylvania, 1998; pp 1-110.

 

 


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