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

EAS in the Research Community

"Bromination from the Macroscopic Level to the Tracer Radiochemical Level: ⁷⁶Br Radiolabeling of Aromatic Compounds via Electrophilic Substitution"


         -The aim of the research accomplished in this article was to explore the differences between the oxidative bromination reaction under small-scale macroscopic vs tracer level radiochemical condition, explored in terms of effective brominating agents. The development of experimental protocols for successful radiobromination at the tracer NCA-scale should be applicable to the synthesis of other radiobromine-labed organic compounds such as PET radiopharmaceuticals and radiotherapy agents. Bromine-labeled compounds have advantages over iodine-labeled compounds; the stronger C-Br bond results in less dehalogenation, and unlike iodide, bromide does not accumulate in the thyroid. 


They found that ipso substitution by electrophilic dematallation effectively "introduces radiobromine regiospecifically into organic compounds containing aromatic rings, but competition can occur with other reactive sites, such as open positions on an activated aromatic ring and amine or amide groups."


 In one particular reaction hydrogen peroxide/acetic acid(2:1) was used in the radiobromination of a 5-tributytin substitutud furfural, in in which the electron-rich furan ring is deactivated slightly by the aldehyde group to make the compound in Image 1. It was used in the synthesis of 76Br-labeled progestin 16alpha, 17alpha-dioxolane for breat tumor imaging and radiotherapy. 


                                                                           (Image 1)

Source: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2743097/?tool=pubmed

Aromaticity description for non-science nerds

               While the specific chemical and physical reasons as to what determines “aromaticity” or if a compound is aromatic is difficult to understand without having taken a year of college chemistry, the basic structure can be understood easily enough. Molecules must be cyclic, which is any polygon shape. There can't be a break in the shape, thus each side must touch two other sides. Next the compound must be completely conjugated which means that there is no more than one bond between each double bond. Bonds are represented by a line in a line-angle structure(see picture), and double bonds are represented by a double line. These compounds actually share those double bonds so each bond has a bond order of 1.5, thus a more accurate depiction would have a double bond on each carbon (corners of the compound), but for visual aid they are only on every other carbon. A classic example that depicts these explanations is the benzene ring (figure 1). Notice the double lines(double bonds) as well as how they are actually shared by all of the carbons(corners of the internal structure) illustrated by the bottom image.                                   

                                               (Figure 1- Benzene Resonance Structures)

             

              Finally, they must have a multiple of 4n +2 pi electrons. Each double bond contains 2 pi bonded electrons so by counting the double bonds one can determine the amount of pi electrons. For example the two dimensional structure of a benzene ring has alternating double bonds thus it has six pi electrons(see figure 2), which is a multiple of 4(n) +2=6, where n=1. In this compound, each carbon is sharing the electrons that belong to the Hydrogen (H) and each Carbon to which it is connected. This type of electron "sharing" is called covalent bonding. Pi bonds are covalent chemical bonds where two lobes of one involved electron orbital overlap two lobes of the other involved electron orbital.

                                                            (Figure 2- Benzene Orbitals)

Resource:

1. Janice Smith,Organic chemistry. 3rd. New York City: McGraw-Hill Companies, 2008. pg 616-618

2. Benzene Resonance Structures. February 24, 2011. http://en.wikipedia.org/wiki/File:Benzene_resonance_structures.png

3. Benzene Orbitals. February 24, 2011. http://en.wikipedia.org/wiki/File:Benzene_Orbitals.svg

Response to Test #1

Although the test was very challenging, after looking back over sapling I realized the percentage of problems from each section mimicked that of the test. The only problems on the test I do not believe we had experienced before were questions 18 and 20. In those, we had to write the molecular ion and any other important peaks(due to fragments or M+1, M+2) for five different compounds written in C10H14N2 form instead of in the structural form. Due to the multiple examples of determining the number of unique CNMR and HNMR signals for compounds as in problems 15 and 16 on sapling I had expected another one of those problems on the test. We did receive a HNMR question of similarity but not a CNMR question.

Going back to the molecular ion and important peak question I could have figured it out with a few more minutes of time but because of the other time consuming  questions on the test I could not. Over all I believe the difficulty of the test did not match the test restraint we were given. I barely finished writing the last question before the 50 minute time period expired and could not adequately answer them. But I do understand we are in a very advanced college science course so the difficultly is expected. 

The Muddiest Mud of Ch. 13

Although chapter 13 in Smith explains the function and technique of a Mass Spectrometer, the book does not contain a picture of an actual Mass Spectrometer. So the muddiest point of the chapter concerned what an actual Mass Spectrometer looked like. As instructed in Smith, a mass spectrometer vaporizes a sample and bombards it by a beam of electrons to form an unstable radical cation, which then decomposes to smaller fragment. Then the positively charged ions are passed through a negatively charged plates and then go through a curved analyzer tube in a magnetic field. This magnetic field causes the ions to deflect by different amounts due to their ratio of mass to charge, which is then plotted by a computer on a mass spectrum of m/z.

JEOL, a global scientific Analytical Instrument company, produces a few different types of Mass Spectrometers. One model JEOL produces is the AccuTOF DART(Image 1). DART stands for direct analysis in real time. This machine allows for analysis of solid, liquid, and/or gaseous sample at atmospheric pressure and ground potential by simply placing the sample between the DART and the mass spec. By reporting the exact mass measurements together with precise isotopic abundances can rapidly identify unknown compounds by their elemental compositions.


                                                  (Image 1: AccuTOF DART)

Sources: 

1. Janice Smith,Organic chemistry. 3rd. New York City: McGraw-Hill Companies, 2008. pg 463

2. JEOL. AccuTOF DART. 2011 http://www.jeol.com/PRODUCTS/AnalyticalInstruments/MassSpectrometers/AccuTOFDART/tabid/141/Default.aspx