Dr. Glaser's "Chemistry is in the News"
To Accompany Bruice, Organic Chemistry, 3/e.
Chapter 4. Stereochemistry: The Arrangements of Atoms in Space; the Stereochemistry of Addition Reactions.

Editorial Comments

We learned a lot from the thalidomide experience! Had we only known before!! As you know from the box entitled "The Enantiomers of Thalidomide" of Bruice's text Organic Chemistry, 3/e, stereochemistry is an essential aspect of a drug. The dextrorotatory enantiomer has the desired sedative properties but the levorotatory isomer is highly teratogenic. More recent studies have shown that even the "good" isomer is mildly teratogenic since racemization occurs in vivo.

Nowadays, for a drug to be approved, the effects of all the stereoisomers present need to be explored and fully tested or, better yet, the drug needs be generated as a single enantiomer. Pure and -- all too often -- not that simple!

Take taxol, the star drug of the current news item. Taxol is a complicated and fascinating molecule. Two of my students here at MU, Michelle Azu and Justin Esses, researched taxol as part of their honors' project for Chemistry 210, Introduction to Organic Chemistry, the course I taught in the Winter Semester of 1997. Justen and Michelle wrote their report in form of a web site. Take look at their site on taxol (this site requires the CHIME plugin).

Questions

Questio n1: What aws thalidomide used for in the 1950s?

Answer 1: Morning sickness.

Question 2: Explain using structural formulas why even the "good" stereoisomer of thalidomide is mildly teratogenic.

Answer 2: Racemization occurs.

Question 3: What patients are being treated with taxol?

Answer 3: Cancer patients. Ovarian cancers. Breast cancers. AIDS patients with Karposi's sarcoma.

Question 4: How many chiral centers are there in taxol. You may search for the answer by looking at the molecular model on Justin & Michelle's web site, or you may examine the structural drawing in their link "History", or, perhaps, you might come across the number while reading the text.

Answer 4: There are 11 stereocenters. A difficult synthesis target indeed.

Chemistry & Society.
Question 5: This question is meant to start a discussion. Perhaps you can discuss this question with your peers (i.e. on the course discussion list). Here is the question: The need for the drug taxol resulted in significant ecological concerns. State what these concerns are and recognize the value of modern organic synthesis to overcome these concerns.

Possible Answer to Question 5: Taxol occurs in the bark of the Pacific yew tree. Harvesting the drug kills the trees and diminishes the ecosystem. Thus: Synthesize taxol and leave the trees untouched.