s isomer

Molecule of the Day: Thalidomide

Thalidomide (C13H10N2O4) is a white powder that is insoluble in water under standard conditions. It was marketed in the late 1950s to the early 1960s as a morning sickness drug for pregnant women, but eventually gained infamy and was withdrawn from the market after it was shown to be responsible for many congenital defects in infants whose mothers consumed it.

Thalidomide was first developed in West Germany during the 1950s, and was found to be a highly effective antiemetic (drug that reduces vomiting and nausea). It was then marketed as a drug to treat morning sickness, which is a common physiological effect of pregnancy. As drug testing regulations were less stringent then, extensive human trials were not required for drugs to be produced and sold. Some companies even claimed that thalidomide was “completely safe” and had “no adverse effect on both mother and child”.

However, this was proven wrong, and thalidomide was withdrawn from the market in most countries in the early 1960s due to public pressure. Sadly, it was too late; an estimated 10,000 children were born with deformities during this period due to their mothers’ thalidomide usage. Birth defects caused by thalidomide included heart and eye deformities, underdeveloped or missing limbs, as well as brain damage.

It is believed that thalidomide produces these effects by binding to cereblon, a protein that is critical in limb formation and myeloma cell proliferation in foetuses. Additionally, it inhibits angiogenesis (the development of blood vessels), which is critical in the formation of limbs as they contain highly complex systems of blood vessels.

While the S-isomer (below right) of thalidomide was found to be responsible for these congenital defects, the problem cannot be solved by administering the R-isomer (below left); thalidomide racemises in the body to form a mixture of stereoisomers via keto-enol tautomerisation. Hence, S-thalidomide will still be formed in vivo even if pure R-thalidomide is administered.

To synthesise thalidomide, phthalic anhydride and glutamic acid are first reacted to form the corresponding phthalimide, which is then dehydrated to form the cyclic acid anhydride. It is then reacted with urea to produce thalidomide.

Requested by anonymous

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anonymous asked:

remember that stereochemistry can be every important for aromachemicals, even hydrocarbons!

Absolutely! 

The R-isomer of carvone (below) smells like mint, while the S-isomer smells like caraway seeds. Fascinating, isn’t it? It shows that the binding sites of the olfactory receptors in our noses are chiral too!