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)