Total Synthesis of CP Compounds
Man's fascination with the many uses that can be found with the exploitation of natural substances has been demonstrated time and again throughout history, but the stage was set at the turn of the century for organic chemists to begin to focus on utilizing natural compounds for the benefit of medicinal and industrial uses. The discoveries of penicillin, aspirin, and other naturally occurring useful compounds in the earlier parts of the century set the stage for the utilization and exploitation of biologically active compounds as a molecular science. However, there are limits as to how much we can do with what nature provides us. This puts the role of the synthetic organic chemist at the forefront of synthetic compound synthesis technology. KC Nicolaou is one such leader. The main goal of Nicolaou's lab is the complete synthesis of naturally occurring compounds, along with solid phase chemistry, molecular design, combinatorial synthesis, and biological investigations; some of the results of Nicolaou's work include: the total synthesis of the anticancer agent Toxol, the marine neurotoxins brevetoxins A and B, the anititumor agents epothilones A and B, eleutherobin and sarcodictyins, the antibiotic vancomycin, the cholesterol-lowering CP-molecules, the immunosuppressant agent sanglifehrin A, the antibiotic everninomicin, and a number of bisorbicillinoids such as trichodimerol, bisorbicillinol, and bisorbibutenolide. Another example of Dr. Nicolaou's work is a paper published in Chemistry International entitled The Absolute Configuration and Asymmetric Total Synthesis of the CP Molecules (co-authored by Jae-Kyu Jung, Won Hyung Yoon, Yun He, Yong-Li Zhong, and Phil Baran.) In this paper, Nicolaou and his associates describe how their goal was both the total synthesis of these CP compounds (achieved in 1999) along with the determination of their absolute configurations; methods used in initial attempts to determine absolute configuration at different carbons included X-ray crystallography and NMR. Nicolaou set about synthesizing this compound by thinking through possible reactions that he might use to begin to build the carbon skeleton needed for this molecule. His team decided on a type-II intramolecular Diels-Alder reaction as the key step to generation of the core skeleton. The Diels-Alder reaction utilizes a dienophile in order to form new carbon-carbon bonds in a single step, in this case to form multiple ring structures. However, Nicolaou ran into trouble when several reagent-based enantioselective approaches with the precursor failed to yield appreciable levels of the desired product. After much study of this problem, Nicolaou's team came to the conclusion that a Lewis acid catalyst would be their best shot at inducing the asymmetry needed for this particular absolute configuration.
The experiment of Diels-Alder reactions, in particular the furan and maleic anhydride as used in my experiment, observed the exo product as oppose to the exo product. This shows the tendency for the stereochemistry of the Diels-Alder to yield an exo product in preference to the endo product. To determine the stereochemistry, a melt temperature of the product was taken and compared to literature values. The melt temperature for the product was roughly around 113oC, corresponding to the exo Diels-Alder product of furan and maleic anhydride. When compared to the class data of melting ranges, the melting temperature from the reaction was relatively consistent to the majority. Based off this, the assumption can be made that the Diels-Alder prefers
The 1H NMR spectrum shows that there are 18 protons in 11 different proton environments. This fits with the Diels-Alder reaction taking place a...
This week’s lab was the third and final step in a multi-step synthesis reaction. The starting material of this week was benzil and 1,3- diphenylacetone was added along with a strong base, KOH, to form the product tetraphenylcyclopentadienone. The product was confirmed to be tetraphenylcyclopentadienone based of the color of the product, the IR spectrum, and the mechanism of the reaction. The product of the reaction was a dark purple/black color, which corresponds to literature colors of tetraphenylcyclopentadienone. The tetraphenylcyclopentadienone product was a deep purple/black because of its absorption of all light wavelengths. The conjugated aromatic rings in the product create a delocalized pi electron system and the electrons are excited
A chemical reaction is a process in which the rearrangement of the molecular or ionic structure of a substance is transformed physically or chemically. If the reaction occurs, the starting products will always be different from the products. They also involve the motion of electrons which leads to buildup and breakdown of chemical bonds. There are six types of chemical reactions including Synthesis, Decomposition, Single Replacement, Double Replacement, Combustion, and Acid Base. Each reaction has their own unique characteristics that make them special.
However, it provided insight in the context of Diels-Alder reaction at that time[8] and confirmed the morphine structure proposed by organic chemist Robert Robinson[9]. As a result, many chemists eventually discovered an efficient way to produce morphine. The most prominent of which was developed by Kenner C. Rice which proceeded to make 30% of the product with 14 steps[10]. His method is based on the biomimetric route that follows the Grewe cyclization which corresponds to the morphine biosynthesis[10], as illustrated in Figure
In the middle ages, Antipyretic agents (for preventing or reducing fevers) were compounds found in the bark of white willow and cinchona trees. Alternatives to this were eventually sought for in the 1880s as the cinchona tree had become scarce. In the 1880s, the development of alternative antipyretic agents began to develop acetanilide in 1886 and phenacetin the following year. At this point in time, Harmon Northrop Morse had already synthesized
To build acene backbone the Diels-Alder reaction can be used. Byproduct free [4+2] cycloaddition is especially enticing due to the fact that in the employed synthesis strategy the starting diene is not purified before the reaction. To synthesize diene bisacetal decomposition is deployed. The initial reaction is employing diketone which forms acetal with methanol under acidic conditions. To shift the equilibrium of reaction to the products direction, the three times excess of methyl orthoformiate is introduced.
Click chemistry was created by taking cues from how nature naturally reacts. 1 The goal of Sharpless and colleagues was to create a number of selective blocks that could be connected in many different ways with the ability to work in many various applications. 1 For a reaction to be defined as click chemistry: “the reaction must be modular, wide in scope, give very high yields, and generate only inoffensive by products that can be easily removed” and it must have undemanding reaction conditions. 1 The high thermodynamic driving force of the click reaction is the reason click reactions are able to achieve their specified characteristics.1 High selectivity for a lone product and a rapid completion of the reaction is another feature of click reactions. 1 The formation of carbon-heteroatom bond reactions cover the majority of examples of click chemistry including cycloadditons of unstaturated species nucleophilic substitution reactions, non-aldol carbonyl chemistry , and addition carbon-carbon multiple bonds. 1
Humanity has come a long way from our first steps on this Earth with accomplishments such as medicine, industries, factories, etc... Not too long ago though, a new type of method called for developing resources called “synthesization” took the chemistry field by storm with the creations made possible like never before. Certain individuals, such as Percy Lavon Julian, have used the method of synthesization to explore new ways of creating limited or rare resources. Percy Lavon Julian was an African American who, despite being faced with racial prejudice, was able to create synthetic products that people are positively impacted by today because of their availability and low cost.
Schachman, H. (March 17, 2006). From “Publish or Perish” to “Patent and Prosper”. The Journal of Biological Chemistry, 281, 6889-6903. doi: 10.1074/JBC.X600002200.
Most of the drugs in use today have come from nature. Three common examples include aspirin, morphine, and penicillin. “‘In the old days you could wander around a corn field or up in a forest, take little dirt samples, bring them back to the lab—and what do you know? You’d found microorganisms that produce streptomycin, or actinomycin, or...
J. Clayden, N. Greeves, S. Warren, P. Wothers. Organic Chemistry. 8th ed. 2007, Oxford University Press, p. 1186-1191.
From analgesics to chemotherapy, over the years Medicinal Chemistry has helped treat a range of diseases and pathogens. My reasons for wanting to pursue a career in this field stem from my fascination with how drugs function and recondition imbalances in the human body. How a tiny tablet, so small and insignificant looking, can at times achieve such life-enhancing results.
Miller SL, and Urey HC. 1959 Organic Compound Synthesis on the Primitive Earth. Science 130,
Natural products, in general terms, are chemical substances produced in nature1. Or simply putting it, they are molecules found in living organisms, according to Mcmurry2. Natural products are secondary metabolites, which are small molecules living in the organism without effecting in a major way, like nucleus acids, which are essential for the survival of the organisms19. While many of them don’t have a specific biological role, some of them act as sex attractants and anti-feedants19. They differ with other biological micro molecules in their complexity, since they are much smaller than average micro molecule, tend to be more diverse and have the ability to conserve themselves for a long period of time even without a specific biological activity or role19. The importance of natural products relay on its variety of uses, since natural products are used in pharmaceutical industry, food production and pesticides3. The techniques commonly used to produce natural products are: Column chromatography, extraction and distillation. In this paper, the efficiency of the extraction method in synthesizing natural products will be evaluated. Extraction of natural products in an economic and environmentally-friendly way is of high importance to all industries involved.