[VladimirPutin]

Hello!

I have rudimentary organic chemistry knowledge and I am trying to understand the drug Lipitor. I have researched thoroughly about Lipitor but this complex molecule continues to leave me baffled and confused. I have been particularly struggling with these questions:

Describe the molecular structure. (It's such a ginormous molecule I don't know where to start, I also don't know how to determine the bond angle or VESPR shape. I found this link, which potentially looks helpful but it's Ancient Greek for me:http://www.pfizer.com/files/products/material_safety_data/PD009.pdf. I need the most help with this question.)

Describe the synthesis process. (I have found sources but it's so long and I am very confused by how it's synthesize and I am unsure which steps I have to emphasize, plus I need to explain this in terms that others would understand, while giving a presentation under 15 minutes.)

Describe mechanism of action of the drug with biological site of action.

Sources I have found:
http://www2.chemistry.msu.edu/courses/cem958/FS06_SS07/Amand.pdf
http://newdrugapprovals.org/2013/08/23/atorvastatin-synthesis/
http://blogperso.univ-rennes1.fr/pierre.van-de-weghe/public/synthesis_of_commercial_drugs_2011-12_-_M2_Hanoi.pdf
http://www.fda.gov/ohrms/dockets/ac/06/briefing/2006-4254b_16_02_KP%20Atorvastatin%20Label%20FDA%208-7-06.pdf

Thank you very much to all those willing to help out a confused student!

[Arkcon]

Well, your sources are good, and quickly entering trade names into Wikipedia usually pops up the name:  http://en.wikipedia.org/wiki/Atorvastatin  Lets try to work out the answers to your question, but you really should be more specific about what you do know, and what answer specificity you need.

Describe the molecular structure

You can see it spinning in a space filling model on Wikipedia.  Maybe you just need to name the basic functional groups?

Describe the synthesis process

I don't know what to emphasize either.  Why would you emphasize some part over others?

Describe mechanism of action of the drug with biological site of action.

http://en.wikipedia.org/wiki/Atorvastatin#Mechanism_of_action  That might be too obtuse for you as well, but you have to start somewhere.  Make an outline -- for each word that you don't understand, look it up on Wikipedia.  Wikipedia's good for that.  Or you can instead ask yourself, what does this medicine do?  And try to figure it out that way.

[Dan]

It sounds like you are way out of your depth, but I can give you some suggestions.

What class is this for? Do you have to cover this topic or did you choose it yourself?

Describe the molecular structure.

What functional groups are present?
Are there hydrophobic and hydrophilic regions present?
Are there hydrogen bond acceptors/donors present?
In terms of shape, can you identify which parts of the molecule are flat and which are not?
Is there any sterochemistry?
Which parts are conformationally flexible or rigid?

Describe the synthesis process. (I have found sources but it's so long and I am very confused by how it's synthesize and I am unsure which steps I have to emphasize, plus I need to explain this in terms that others would understand, while giving a presentation under 15 minutes.)

It will be pretty much impossible for you to explain the key steps to a layman audience unless you have a good understanding of organic chemistry. Nevertheless, I will offer some suggestions...

Split the molecule into different fragments, then show how each fragment was made and how they were connected to each other.

You could look up the concept of "retrosynthesis" - this is generally how chemists visualize synthetic strategies. However, I used this approach in a presentation to biologists recently and it caused a lot of confusion. So it may not be the best approach for you.

This is probably too detailed for your purposes, but for a recent enantioselective synthesis of atorvastatin, see: Lam Angew. Chem., Int. Ed. 2014, 53, 4186-4190 Link

Describe mechanism of action of the drug with biological site of action.

You have posted some pretty good resources there... can you explain in your own words how you understand it to work?

[VladimirPutin]

@Dan Thanks for responding! Could you please help my identify the answers to those questions, those would be a great starting point?

@Arkcon I want to emphasize, because it's such a long process and I don't have time to go over every step.

[Babcock_Hall]

VladimirPutin,

I would interpret the biological site of action to mean the receptor or enzyme to which lipitor binds, though it could conceivably refer to a sub cellular location.

[Dan]

@Dan Thanks for responding! Could you please help my identify the answers to those questions, those would be a great starting point?

You have to show an attempt - that is a Forum Rule - and we can take it from there.

Start with the easy one:

What functional groups are present?

[VladimirPutin]

There's a carboxyl group, amide group, and 2 alcohol groups. Please let me know if I'm missing any! Also, I was able to do the whole mechanism, but that synthesis...

[Arkcon]

VladimirPutin:, i thought its been implied enough, but now I feel the need to tell you explicitly -- You're not asking useful questions, and we can't understand how to help you.   This is likely your assignment, and you're required to do most of the work.  Note: you found some links, but that isn't work.  Sometimes people come without even doing that much, but it is up to you to read them, and write ... whatever you're meant to write.

I have rudimentary organic chemistry knowledge and I am trying to understand the drug Lipitor.

That can't be done.  That is like saying, "I learned to drive a car yesterday, please explain to me now how to fly a MiG"

Also, I was able to do the whole mechanism, but that synthesis...

This statement, what does it mean?  What can you do?  What can't you do?

[VladimirPutin]

That can't be done.  That is like saying, "I learned to drive a car yesterday, please explain to me now how to fly a MiG"

Well, that is what I am expected to do.

http://www2.chemistry.msu.edu/courses/cem958/FS06_SS07/Amand.pdf

What could really help me if someone were to explain the slides from "The Decision of the Core Template" to "The Birth of Lipitor" and from "Pfizer's Commercial Route: Fragment A" to "Pfizer's Commercial Route". If possible, could you explain it as if you were giving a presentation among your colleagues? I would like to specifically know the mechanism of action, if its SN1 or SN2, why does it use liquid nitrogen, why is it toxic, why this template works and another doesn't. I am completely lost in understanding it, and I need as much help as possible.

Even if you can only do a couple of slides, please post your explanation for those! It would be extremely helpful! I promise I give all those who help a mole snack lol.

[Dan]

What could really help me if someone were to explain the slides from "The Decision of the Core Template" to "The Birth of Lipitor" and from "Pfizer's Commercial Route: Fragment A" to "Pfizer's Commercial Route".

No. That's not how it works here. You are asking someone to teach you 2-3 years of undergraduate organic chemistry. It is not possible to do do that on an internet forum.

Your questions are simply too vague and imprecise.

I have tried to break up some of your questions into smaller more precise questions, and have asked you to try to answer them. Until you do that, I can't help you. We can help you help yourself, but nobody is going to dump a presentation in your lap for you to copy (see Forum Rules[/]).

[Arkcon]

Dan: is absolutely correct, and I suspected there was no way for us to help, that is, give you useful hints to help you solve this problem for yourself.  I'm still puzzled as to what the question is.  You have a perfectly good presentation to help an experienced organic chemist and molecular biologist under the drug Limiter.  What are you to do?  Simply for high school kids or non-scientists?  Why?  This topic is too advanced.

[orgopete]

I don't think this should be as difficult as the poster is making out. A first clue is a 15 minute presentation and the poster is acknowledging a rudimentary knowledge of organic chemistry. I should therefore assume the others in the class do not know a lot of organic chemistry either. This virtually begs to ask, "Why Lipitor?". I might anticipate this taking 15 minutes to explain. (It should not focus on a synthesis that the poster or the rest of the class do not understand and therefore not will not find interesting.) Imagine that students in the class don't even know what it is and start there.