simvastatin synthesis

Question 1

what is is added to lovastatin to turn it into simvastatin?

Answer 1

a methyl group

Question 2

list the steps of converting lovastatin to simvastatin?

watch lecture 4 from the 2:40 mark

Answer 2

So first of all, we add an amine (RNH2), which reacts with the ester group to open up the cyclic ester on the lovastatin molecule.

and then a protection group insneeded which is A StBU(Me)2SiCl

Question 3

list the steps of converting lovastatin to simvastatin?
go to the lecture slide and see if you can describe the steps?

watch lecture 4 from the 2:40 mark

Answer 3

1. So first of all, we add an amine (RNH2), which reacts with the ester group to open up the cyclic ester (lactone) on the lovastatin molecule.
2. And then a protection group in needed which is a silane (tBU(Me)2SiCl) which reacts to and protects the Oxygen in the OH group formed after the cyclic ester is opened up to while the H and the Cl breaks off and forms HCl. this is to protect the lactone which is very reactive from the steps 3 and step 4. so making this protective part very important.
3. Next we have a strong base added, which attacks and takes away the (proton) hydrogen atom in the position where we would want to add the methyl group forcing the carbon to form a carbanion( due to only forming three bonds instead of four).
4. The carbanion is then reacted with a halogenoalkane preferably (methyl halide: MeX) the halide being a good leaving group breaks of and reacts with the negative charge on the carbanion while the methyl group goes on to replace the proton that left in the last stage. Forming two methyl groups on the last carbon.
5. finally the protective group is taken of and reforming the lactone ester ring this is done by reacting with:
   ❺ aq. HF
   ❻ NaOH
   ❼ 100 °C