[ubiqman]

I know that thalidomide naturally undergoes in vivo racemization and acid hydrolysis, which is the reason why it is teratogenic. As far as I know, apremilast is one analog of thalidomide that doesn't undergo racemization due to its lacking of an acidic chiral proton. However, it does undergo hydrolysis, which could still lead to a teratogenic product. I guess my main question is what structural features lead to the hydrolysis of thalidomide/its analogs, and is there an analog that doesn't undergo either racemization or hydrolysis?

[kriggy]

As far as I know all are glutamic acid deriativies, except for apremilast. Also, apremilast proton at chiral center is also somehow acidic due to the presense of the pthalimide moyety althought is likely not as acidic as the other derivatives. The hydrolysis thing is just because of the pthalimide, they can be hydrolyzed. Im not 100% sure on this but likely the protonation of the carbonyl group deactivates the nitrogen lone par via conjugation and then the water can attack the other carbonyl and kick out the amine