The LAST ONE!

After two semesters of Organic Chemistry, this blog entry will be my final episode of the epic journey through the long and hard days of Organic Chemistry, the nemesis of every pre-med student!

In Christina White's of the University of Illinois website for organic reactions, she presents many catalytically driven reactions that correspond directly with the topics of Chapter 26 in our Organic textbook by Smith. I picked publication #5 entitled "Poly Synthesis Through Hydrocarbon Oxidation: De Novo Synthesis of L-Galactose" by D.J. Covell, N.A Vermuellen, N.A. Labenz, and M.C. White.(1) I attempted to upload the picture but the quality of the copy was not worth publishing, the picture can be found by going to the link in the sources. They describe conditions that allow p-anisic to act as a nucleophile for the linear allylic oxidation reaction to generate compound 4 in the reaction scheme. This reaction was carried out with a Palladium catalyst in DMSO. Unlike the Heck reaction we learned about in Ch 26 of Smith, this reaction oxidized the original p-anisic acid with an ester. The Heck reaction involves the coupling of a vinyl or aryl halide with an alken to form a more highly substituted alkene with a new C-C bond.(2) The similarities between the two reactions are that both use a Pd catalyst to attach a new functional group to the compound. In this reaction, the alkene of the compound was not oxidized, alkene turning into a -OH group, until the last step. This was accomplished by asymmetric dihydroxylations (AD). In closing for the final time, by the end of two semesters of Organic Chem I can actually comprehend the actions of this reactions and how to identify each step, so I guess all that studying was good for something...

Adios Chemistry Blog world!
          -KAMetz


Sources:
1. Covell, D.J et al. Polysynthesis through Hydrocarbon Oxidation: De Novo Synthesis of L-Galactose.
ACIEE.2006,45,8217-8220. http://www.scs.illinois.edu/white/index.php?p=publications (accessed May 6, 2011)
2. Janice Smith,Organic chemistry. 3rd. New York City: McGraw-Hill Companies, 2008. pg 1009

We describe conditions that allow p-anisic acid to act as a nucleophile for the linear allylic oxidation reaction to directly generate (4) with good yields (70%) and outstanding selectivities (E:Z = 97:3

Polyol Synthesis through Hydrocarbon Oxidation: De Novo Synthesis of L-Galactose". 
D.J. Covell; N.A. Vermeulen; N.A. Labenz; and M.C. White. 

Possible Test Question out of Ch.24

Included below is a possible test question from Ch.24 involving an Endole reaction.

This reaction is carried to the dehydrated state giving a new alkene group from the spot of the carbonyl group of the aldehyde.

Extra Credit Seminar- Biomarker of exposure and relationship to genetics by Steven Myer, Ph.D

Tobacco smoking during pregnancy has many know harmful side effects to the baby. The child will receive less food and oxygen in vitro. There is an increased risk of miscarriage, stillborn, premature birth, SIDS, and decreased IQ. Also second hand smoke can lead to increased ear infections and asthmas. Almost all the chemicals that are discussed in a general Organic Chemistry college level course are found in tobacco smoke. As the child is exposed to the smoke, there is a great increase in asthmatic syndrome and bronchitis. But the most harmful time comes in the 1st 6-9 weeks of the pregnancy, with the common cleft palate development. 

Because of the over 4000 chemicals in tobacco smoke, there must be a way to study the effects without testing for each in particular. Biomarkers are molecular, biochemical, or cellular alterations that are measurable in bio media, ex: human tissues, cells, fluids. Molecular epidemiology studies biomarkers in a group which must have specificity, sensitivity, and practicality. An important aspect of this field is the toxicological paradigm. The paradigm is as follows; exposure to internal dose to Biological effective dose to early biological effect to altered structure/function and finally disease. A good biomarker is early in the paradigm

There are certain criteria for biomarkers. There must be a relationship between biomarkers and the disease. They must appear at a defined stage of the disease process. Finally they involve non invasive collection techniques such as sputum or urine collection. Amniotic fluid serves as an effective biomarker in the 1st trimester. In tobacco smokers, they have an increase level of 1-hydroxypene which is a non-carcinogen. This is one such biomarker that can be tested in vitro. Another important biomarker for studying the effects of smoking on the baby in vitro is hemoglobin. By matching the maternal and cord blood of the baby, levels of both can be compared. Globin acts as a nucleophile while tobacco acts as an electrophile. They stay bound for 128 days which is the live of an erythrocyte. 

Finally, 4-Aminobiphenyl is a very powerful carcinogen and there is a direct correlation between the levels in mom and baby. The babies weight decreases as the levels of this chemical increases. Strangely, while there is no significant difference in the levels in across the African or American census, there are decrease levels in hispanics. 

Dr. Myers presented the information in a clear and effective way. Since he is one of the professors of pharmacology at UofL medical school, his lecture increase my desire to head to my goal of D.O school and can't wait to learn about this types of topics all school year.

                                            (4-Aminobiphenyl)

Hell-Volhard-Zelinsky Halogenation

The Hell-Volhard-Zenlinsky Halogenation reaction causes a halogenation of carboxylic acids at their alpha-carbon, the carbon directly attached to the carbon containing the double bonded oxygen, carbonyl carbon. PBr3  initiates the reaction as a catalyst, after which one molar equivalent of Br2 is added. The PBr3 replaces the carboxylic OH with a bromide, resulting in a carboxylic acid bromide. This can then tautomerize, which switches the double bond and the hydrogen of the carboxyl group to create an enol, and will readily react with the Br2 to brominate a second time at the alpha position.(1)

(Image 1: General Reaction mechanism of the Hell-Volhard-Zenlinsky Halogenation)(2)

In one particular study, racemic [9,10-³H]-2-bromopalmitic acid was synthesized from [9,10-³H]palmitic acid by a Hell-Volhard-Zelinsky reaction. The bromopalmitate was found to be an effective tracer for assessing tissue specific plasmas free fatty acid (FFA) in vivo. Palmitic acid(image 2) was treated with excess bromine and PCl3 at 80 degrees Celsius overnight. The reaction was quenched with water and then bromine was removed by evaporation. By adding a bromide to the alpha carbon of palmitic acid, bromopalmitate was created. (3)
(Image 2: Palmitic acid)(4)

Sources:
1. http://en.wikipedia.org/wiki/Hell-Volhard-Zelinsky_halogenation
2. http://www.organic-chemistry.org/namedreactions/hell-volhard-zelinsky-reaction.shtm
3.http://www.jlr.org/content/40/6/1155.full#ref-23
4.http://en.wikipedia.org/wiki/Palmitic_acid

My Ester: Glucono delta-lactone

Glucono delta-lactone (GDL) is a cyclic Ester, lactone, is a naturally occurring food additive. The FDA approved uses of the ester include use as a curing and pickling agent, leavening agent, pH control agent, and sequestrant which is a food additive whose role is to improve the quality and stability of the food products. Pure dry GDL is a white odorless crystalline powder. Although GDL is neutral, the hydrolyzed form is gluconic acid which is acidic.Gluconic acid occurs naturally in fruit, honey, and wine. This acid adds a tangy taste to food and is roughly a third of the sourness of citric acid. It is metabolized to glucose. One gram of GDL yield roughly the same amount of metabolic energy as one gram of sugar. 


With the addition of water the ester is partially hydrolyzed to gluconic acid, forming a chemical equilibrium between the lactone form and gluconic acid. The rate of hydrolysis will increase with increasing temperature and high pH.  Thus it is soluble in water. Also the melting point of GDL is 153 degrees Celsius. 


I could not find the exact carboxylic acid/ alcohol pair GDL is derived from, I believe it can be synthesized from glucose since it has the same amount of carbons as glucose and hydroxy groups. It simply has to be hydrolyzed.




Sources: 
1. http://en.wikipedia.org/wiki/Glucono_delta-lactone
2. http://www.ams.usda.gov/AMSv1.0/getfile?dDocName=STELPRDC5067074
3. http://en.wikipedia.org/wiki/Glucose

Grignard Reaction

Our assignment for this week's blog was to find an experiment carried out involving the grignard reaction, organolithium, or organocuprate reactions in at least one synthetic step. The Grignard reaction is an important tool in the formation of carbon-carbon bonds and for the formation of carbon-phosphorus, carbin-tin, carbon-silicon, carbon-boron, and other carbon-heteroatom bonds. This type of reaction acts as nucleophiles and attack electrophilic carbon atoms that are present within polar bonds, carbonyl groups for example, to yield a new carbon-carbon bond. The reaction I found involved the formation of 4-Nonylbenzoic acid. Below is the overall reaction of the experiment.

In this experiment, the grignard reaction takes place in part A. The nonylmagnesium bromide/Fe(acac)3 catalyst then THF for 7 min in 0 degrees celsius, replaces the Chloro group on the benzene ring with the 9 carbon chain, nonyl group. The IUPAC name of this product in A is 4-nonylbenzoic acid methyl ester. Expensive noble metal catalysts were replaced in this experiment by cheap, air stable, commercially available and toxicology benign iron salts without any loss in efficiency, using inexpensive Grignard reagents as the preferred coupling partners. "When applied to polyfunctional substrates, iron catalyzed reactions allow either for selective, exhaustive, or consecutive cross-coupling processes to be carried out in "one pot." (1)




Reference:
1. Furstner, Leitner, and Seidel. 4-Nonylbenzoic Acid. Organic Syntheses, Vol. 81, p. 33 (2005); Coll. Vol. 11, p.353 (2009)

Lysine- Essential Amino Acid

            Lysin, L-Lysine, amino acid K,  is an essential amino acid, which means the body can not produce it, in humans. It must be taken in through diet or by supplementation.  Lysine was first isolated from casein (a milk phosphoprotein) by Drechsel in 1889.(Walter Kluwer) Lysine is important for proper growth, and plays an essential role in the porduction of caritine, an nutrient responsible for converting fatty acids into energy and helping to lower cholesterol. Another role of lysine involves the absorption of calcium in the body as well as a role in the formation of collagen, and substance important for bones and connective tissues. A common use of lysin is to decrease to proliferation of the herpes virus.

            Foods that are rich in protein are a good source of lysine which include red meat, pork, poultry, cheese, nuts, eggs, and soybeans to  name a few. Low lysine levels symptoms include fatigue, nausea, dizziness, loss of appetite, and anemia. Since  it helps the body absorb calcium and decreases the amount of calcium that is lost in urine, some researchers think lysine may help prevent bone loss associated with osteoporosis. Lab studies suggest that lysine in combination with L-arginine makes osteoblasts more active and enhances production of collagen. (University of Maryland).

         The molecular formula for lysine is C6H14N2O2 with a molecular weight of 146. 19g/mol. It's Isoelectric point(pH) is 9.59 (Kirste) The pH values of each group are as follows: the alpha carboxylic acid group=2.18pH, alpha amino group=8.95pH, and finally the R side chain (CH2)4NH2=10.53pH.(Parrill)

The functional groups on it's side chain include an amino group (NH2) as well as an alkane carbon chain. 

         Lysine's long flexible side-chain with a positively charged end makes it suitable for binding to molecules with many negative charges on their surfaces. "For example, DNA-binding proteins have their active regions with arginine and lysine. The strong charge makes these two amino acids prone to be located on the outer hydrophilic surfaces of the proteins." The alpha amino group often participates in hydrogen bonding as a general base in catalysis. (New World Encyclopedia)

One of the peptides that contains Lysine is the mycobacterial dideoxymycobactin T cell antigens
 which was synthesized to fight TB.

                                                            (Antigenic DDM) 5

Sources:

1.Lysine. Review of Natural Products. factsandcomparisons4.0 [online]. 2005. Available from Wolters Kluwer Health, Inc. Accessed April 23, 2007.

2. Lysine. University of Maryland Medical Center. http://www.umm.edu/altmed/articles/lysine-000312.htm

Accessed March 23, 2011

3. Parrill, Abby. Amino Acid Structures. Michigan state University. http://www.cem.msu.edu/~cem252/sp97/ch24/ch24aa.html

Accessed March 23, 2011

4. http://www.newworldencyclopedia.org/entry/Lysine

5.Young, Moraski, Miller, and Moody. Solid-phase synthesis of mycobacterial dideoxymycobactin T cell antigens