Question

Description: Thalidomide is a drug that was given to pregnant women in the 1950's as a cure for morning sickness. This drug exists as two different enantiomers, with the absolute configuration being either (R) or (s) depending on the enantiomer. Historically, this drug was first given to women in the racemic form (a 50/50 mixture of enantiomers). It was later discovered that one enantiomer of the drug did its job well, while the other enantiomer caused severe birth defects. This resulted in birth defects of around 10,000 newborns. Instructions: Your job for this case study is to investigate this drug, draw each enantiomer and look up which enantiomer it was that caused the birth defects. Using the (R) and (s) notation, clearly assign the absolute configuration of each enantiomer of the drug and report on why one enantiomer lead to these terrible side effects. Please show your work on assigning (R) and (s). lead to these ternble side effects. Pease show

Answer 1

Thalidomide was initially introduced into the West Germany market in 1957. It was chiefly called "wonder drug" and available as an over the counter (OTC) drug. Thalidomide was primarily used as hypnotic or sedative and later it was also used to treat anxiety, morning sickness in pregnant women, especially to control nausea. However, at that time pregnant women who used Thalidomide had given birth to 5,000 to 7,000 infants with a congenital deformity of limbs and this condition called Phocomelia. Among those 5,000 to 7,000 infants, only 40% were survived. Therefore, it was banned in most of the nations in 1961. Later, Thalidomide used to treat Bone marrow cancer and Hansen's disease (leprosy). This drug has an asymmetric carbon at Glutarimide moiety, so it could exist in both R - ( enantiomeric form and S -(enantiomeric form. Rapid interconversion at physiological pH NH N (S) N(R) NH R-(+)Thalidomide S-(-)Thalidomide Thalidomide is readily soluble in water and alcohol, so under phycological conditions these R-(+and S-(-) enantiomers get interconverted very rapidly (possible explanation) So, even though the patient has given R () enantiomer as a drug, after consumption it could get converted into S-(-) enantiomer within in the cytoplasm of the cell The R-(act as sedative, whereas S-(-) act as teratogen and inhibits release of TNF-a, and thus interferes with angiogenesis which results congenital deformity in the newborns. This drug has no enzymatic pathway for its hydrolysis or conversion of enantiomers from one form to another. However the liver enzyme Cytochrome P-450 negligible amount is metabolized by a