Current Topics in Chemistry - Wade - Chapter 5
This news item was created by students James Neels, Brain Swierczek, Jason Brunton and Christopher Hanson as part of their Chemistry 210 Semester Project in the WS99 under the guidance of Prof. Rainer Glaser.

Glaser's "Chemistry is in the News"
To Accompany Wade Organic Chemistry 4/e.
Chapter 5. Stereochemistry.


For each of the following questions, please refer to the following article:

THALIDOMIDE IS APPROVED FOR U.S. USE, WITH STRICT SAFEGUARDS
by Sheryl Gay Stolberg, New York Times, July 17, 1998


Editorial Comments

Thalidomide, the controversial pregnancy drug, was first synthesized in Germany in 1950 by Chemie Grunenthal. The drug went into general use in 1958, and was banned in 1960. Thalidomide was prescribed for morning sickness but its side effects include babies born with shortened and disformed limbs, or phocomelia, and other deformities.

The problem results from chirality and enantiomer issues. One form, the (R)-complex produces the desired effects. However, the (S)-complex is the form that creates the abnormalities when taken during pregnancy (In order to view 3D models of these molecules, download RasMol program). To further the issue, the different forms cannot be isolated. The two enantiomers spontaneously interconvert, meaning that a mixture of all R molecules will quickly become racemic. Derivatives of the drug Thalidomide can be isolated into the desired forms and this fact gives researchers hope that the drug may still provide important medicinal uses.

The article cites that thalidomide may be useful in treating leprosy and mouth ulcers due to AIDS. These practices have been used in the past with success. Thalidomide may be able to treat other diseases as well, such as, cancer and diseases of the eye.

Currently, a company named Celgene has received permission from the FDA to sell thalidomide in a form they call SYNOVIR, which is part of a group of thalidomide derivatives called SelCID.


Pertinent Text References
Chapter 5. Stereochemistry.



Questions

Question 1: Thalidomide was removed from U.S. markets in 1960. However, the article cites other countries in which its use was continued. List two countries that used thalidomide even after the U.S. ban?

Question 2: Go to the structure link on Thalidomide and recreate both forms of the molecule, label
all chiral carbons and state whether the form is R or S.

Question 3: List the former and current uses of Thalidomide.

Question 4: It was stated in the editorial that thalidomide derivatives are used because their enantiomers can be isolated from each other and do not interconvert to form a racemic mixture. With what you know about enantiomer resolution what are some of the possible methods chemists could use to isolate the R form of thalidomide derivatives?

Question 5: The restrictions on the drugs distribution are quite extensive (i.e. pharmaceutical registration, doctor registration, birth control, etc.). The regulations may make thalidomide inaccessible to patients who could use the drug. Do you think these restrictions are just?



Answers

Answer 1: 1.Israel, Brazil, Mexico.

Answer 2: 2.See structure link, self explanatory.

Answer 3: Former-sleeping potion for treating morning sickness and nausea during pregnancy. Current-inflammation suppressant for Cancer and leprosy; treats ulcers and wasting due to AIDS.

Answer 4: 4.Chemists may be using chemical resolution by treating the racemic mixture with an enantiomerically pure product which results in a pair of diastereoisomers. These diastereoisomers may be separated by distillation, recrystallization, or chromotography.

Answer 5: It's your call.