Effient (prasurgel)

The drug I chose to analyze the synthesis of was Effient, which is the brand name for prasurgel. The structure of Effient is shown below:

The paper which describes the synthesis of this drug was not given on the Chemistry By Design website, which was used as a source for this information.The synthesis of Prasurgel consists of three main steps, with a subsequence which is used to synthesize one of the reactants. The first reaction is shown below:

This reaction is an esterification, which we have discussed in class. This is followed by the second reaction:

(Chemistry By Design). This is a standard nucleophilic substitution reaction. The mechanism of this step involves the removal of the hydrogen atom from the nitrogen, which results in the nitrogen atom being negatively charged and a good nucleophile. Thus, when the bond between the halogen, chlorine, in the reactant the nucleophile forms a new sigma bond replaces the halogen (Smith, 2011). The reactant which is used in this second step is not commercially available. Therefore, it is synthesized using a subsequence which is summarized below:

Finally, there is a third and final step which is summarized by the figure below:

This reaction forms a ketone with the use of pyridine, which we have also discussed in class (Chemistry By Design). 

Sources:

Effient (prasurgel). Chemistry By Design. http://chemistrybydesign.oia.arizona.edu/app.php

Smith, J. G. Organic Chemistry, 3rd ed.; Mc-Graw Hill: New York, 2011.

Artificial Amino Acid

This week's assignment challenged us to synthesize our own amino acid. My amino acid is named 2-amino-3-phenyl-butanoic acid and is pictured below:

I would synthesize this amino acid by first reacting 2-phenylpropanol (Chem-Spider) with PCC in order to form an aldehyde which would then be reacted with ammonium chloride and sodium cyanide which would replace the aldehyde with an amino group and a cyano group. This intermediate would then be reacted with hydronium in order to form the final product, 2-amino-3-phenyl-butanoic acid (Williamson). The reaction scheme is pictured below:

We were also challenged to place our artificial amino acid (2-amino-3-phenyl-butanoic acid) within a pentapeptide with four amino acids which exist naturally. The pentapeptide begins with cysteine, continues with glycine, the synthetic amino acid is in the middle, histadine is the fourth amino acid, and the final amino acid is alanine. The pentapeptide is pictured below:

 

Sources:

Chem Spider. 2-phenylpropanol.  http://www.chemspider.com/Chemical-Structure.13657.html

Smith, J. G. Organic Chemistry, 3rd Ed.; McGraw-Hill: New-York, 2008.

Aromatic Substituion Reactions: Some Biological Examples

Lately, we have been studying electrophilic aromatic substitution reactions. We have studied several examples, learned several mechanisms, and performed brominations in lab. After we have understood and mastered the basics, it is important to make connections from these concepts to the world around us. Therefore, listed below are several examples of electrophilic aromatic substitution reactions which occur biologically and are relevant to our everyday lives.

The first example is of the synthesis of Thyroxine, which occurs within the thyroid:

In these reactions, hydrogen ions in the initial reactant are electrophilically substituted by Iodine. The esterifcation of the alcohol also occurs.

A second example is the drug Prontosil, which is converted by intestinal enzymes into sulfanilamide:

In these reactions, a hydrogen atom attached to the aromatic ring was replaced by a ClSO_2 ion.

A third example of electrophilic aromatic substitution is the biosynthesis of vitamin K, an essential vitamin:

As is observed in the figure, the biosynthesis of vitamin K includes the substitution of an R group for a hydrogen atom.

In conclusion, electrophilic aromatic substitution can be expanded beyond what we have learned in class. In many biologically relevant instances, including the three examples listed, these types of reactions become relevant and important to our everyday life.

Each example and its corresponding figure can be found at the following source:
The Department of Chemistry Turk Group. Electrophilic Aromatic Substitution. http://www.drtchemistry.com/CHM_224_files/Chapter%2016.pdf

The Diels-Alder Reaction: A Natural Example

Based upon our previous knowledge of the Diels-Alder class of reactions, we can make some general statements regarding this style of synthesis:

• A conjugated diene in an s-cis conformation reacts with
• A dienophile to form
• A 6-membered ring with one double bond

These basic facts and more are summarized in the following video:

My Little s-Cis Diene (Diels- Alder Reaction Animated) 

We know that this reaction can occur in the lab, but can it happen naturally?

The answer is yes. A photosynthetic fungus, Macrophoma commelinae, synthesizes the compound macrophomate synthase in complex with pyruvate through a three step proccess, the second of the reactions in this process is a diels alder reaction. The entire reaction process is illustrated below:

It can be observed in the figure the starting molecule (first molecule in the second row of the figure), which reacts to form a six- membered ring.
The diene of this reaction is known as 2-pyrone (IUPAC: pyran-2-one) and is illustrated below:

The dienophile of this reaction is ethyl propiolate (IUPAC:  Ethyl acetylenecarboxylate) and is illustrated below:

The reaction conditions of this process also include that the reaction occurs entirely within the fungus itself, and must be catalyzed by the enzyme MPS. 

Sources (In order of appearance):

Video: My Little s-Cis Diene (Diels-Alder Reaction Animated). YouTube. http://www.youtube.com/watch?v=8SfGsNdVV0Q (accessed Feb 03, 2014)

Reaction Article: Ose, Toyoyuki; Watanabe, Kenji; Mie, Takashi; Honma, Mamoru; Watanabe, Hiromi; Yao, Min; Oikawa, Hideaki; and Tanaka, Isao. Inisght into a natural Diels-Alder reaction from the structure of macrophomate synthase. Nautre. 2003, 422, 185-189.

 

2-pyrone: 2H-Pyran-2-one. Pub Chem Compound. http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?cid=68154#itabs-2d (accessed Feb 03, 2014)

Ethyl propriolate: ethyl propiolate. Pub Chem Compound. http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?cid=12182#itabs-2d (accessed Feb 03, 2014)

New Year: A Public Service Announcement

Hello All!

It has been almost an entire year since my first post "Tryptophan" on the blog: "General Chemistry II." As with most years, many things have changed, including the name and purpose of this blog. A lot of chemistry has been studied/learned in the last twelve months! Upon the completion of my General Chemistry II course, I went on to take both Organic Chemistry I, and Analytical Chemistry in the fall of 2013. Therefore, the blog needed a remodel, if only to reflect the growth which has occurred in the last ~365 days. Accompanying the new design is a new title: "Organic Chemistry II." A blog has once again been assigned to me, and in the pursuit of cohesiveness and posterity, I have decided to add on to the final post of "General Chemistry II." Due to the fact that most of the posts from the former identity of this blog will likely have relatively little to do with Organic Chemistry II, this post was necessitated to get the world up to speed on the changes which a year can bring.
Hopefully this will be an exciting semester full of interesting posts and organic chemistry!

-McKenzie