Artificial Amino Acid

This blog was done to show the artificial amino acid that was designed


Synthesis of the Amino Acid



The process shown above is a Strecker synthesis.  The starting material is an aldehyde; 4,4-dimethylpental. The NH4Cl/NaCN forms and alpha amino nitrile that is names 2-amino-4,4-dimethylpentanenitrile.  The H3O+ allows for the amino nitrile to be hydrolyzed to an amino acid.  The amino acid is named 2-amino-4,4-dimethylpentanoic acid.


The pentapeptide structure that is sketched below is in the form CGXHA, in which the artificial amino acid is substituted in for X.





Sources
ACD/ChemSketch
Smith, J.G. Organic Chemistry. 3rd Edition. McGraw-Hill. New York. 2006. pp.1078-1081.

Aromatic Subsitution Reactions- Synthesis of Diazepam

Electrophilic aromatic substitution is the most common reaction of the aromatic compounds.  These reactions begin with the basic reaction of benzene, in which a hydrogen atom is replaced by an electrophile.  An electrophile is electron deficient and readily accepts an electron pair from an electron rich compound.  The same underlying mechanism occurs for every EAS reaction, the only difference is the identity of the electrophile.  The two-step mechanism that occurs is the addition of the electrophile (E⁺) to form a resonance stabilized carbocation and the deprotonation with a base¹.

 

EAS reactions are often used in the synthesis of pharmaceuticals.  The synthesis of diazepam (valium) is a particular example.  Valium is used to treat a wide variety of conditions, anxiety, muscle spasms, and seizures to name a few. 

 

                          ²Synthesis of Diazepam (Valium)

 

In the production of valium (shown above), the starting material is 4-nitrochlorobenzene and phenylacetonitrile.  When treated with NaOH a five membered ring is formed and attached to both molecules, making the new product 5-chloro-2-methylaminobenzophenone.  When treated with (CH₃)₂SO₄ and Fe/HCl 5-chloro-2-methylaminobenzophenone is formed.  The product is treated with an acid chloride and the H on the N is replaced with the electrophile, acetyl chloride.  From there, the final step occurs in which diazepam is formed from the treatment of the product before with hexamine/p-Toluenesulfonic acid (TsOH).

Sources

¹ Smith, Janice G. Organic Chemistry; McGraw Hill Companies, 2011; pp. 642-643.

² Rhodium. Diazepam (Valium) Synthesis.

                http://www.erowid.org/archive/rhodium/chemistry/diazepam

                (Accessed March 4, 2014)

Biological Evidence of a Diels-Alder Reaction

The Diels-Alder reaction was named from German chemists Otto Diels and Kurt Alder.  It is an organic chemical mechanism in which a conjugated diene and a dienophile form a substituted cyclohexane ring.  In these reactions, three pi bonds break and two sigma bonds and one pi bond forms.

                               

                                                                                                                          General examples

                                               

                                      1, 3-diene              dienophile

 

It has recently been found that there are enzymes that mediate the Diels-Alder reaction in secondary metabolic biosynthetic pathways.  One class of natural products that are believed to exhibit this are polyketides.  These are derived from acetate which makes them well-suited for experiments because they are readily available and relatively cheap.  Because of this, a big part of the experimental evidence of Diels-Alder reaction in nature is derived from this class.

 

The polyketide that has been given the most significant attention is lovastatin (chemical structure shown below) because it is a potent inhibitor of cholesterol biosynthesis in humans. 

 

              ¹ Lovastatin structure

 

Chemists have speculated that the enzymes involved in the biosynthesis of lovastatin (11) are similar to those involved in the biosynthesis of fatty acids.[9] They proposed that condensation of acetate units could produce a triene (12) that would undergo an endo-selective Diels–Alder cycloadditon to the decalin (13).²

 

 

² Synthesis of the declan (14) through an in vitro Diels-Alder cyclization of triene (15)

 

In the image above, product 14a is the endo Diels-Alder product while 14d is the exo products.  The reaction mechanism shown took place in the presence of toluene as well as with an acid catalyst.  Under the thermal conditions (with toluene) the endo to exo products were in a 1:1 ratio.

 

These products were in a 19:1 endo-exo ratio under the conditions of a Lewis acid catalyst. There was an absence of 14a in the laboratory cyclization which suggests that the Diels-Alder cyclization in the biogenesis of lovastin could be enzymatic.

 

                                                                                                                                                                                                                 

 Sources

 

¹ http://www.chemspider.com/Chemical-Structure.48085.html?rid=ddf1244a-8bbf-4453-8aea-f6309e2b7e6e

 

² http://www.ch.ic.ac.uk/local/organic/pericyclic/biosyn_da.pdf