/sci/ - Science & Math

[Anonymous No.5715665]

So for my Organic II final my Professor wants us to draw up a synthesis for an assigned drug.

I was given Yaz... drospirenone.

WTF?

How do I approach something like this? Should I synthesis smaller ringer and try to match them?

I feel that the moment I react one reagent it will attack the reset of the molecule... She said that it doesn't need to actually work, it just needs to make sense. Any help is much appreciated.

[Anonymous No.5715678]

Is it just me, or is this ridiculous?

[Anonymous No.5715685]

>>5715678
It's pretty intense. How long ago was it assigned? How complex of a molecule are you allowed to start with?

[Anonymous No.5715691]

>>5715665
steroid synthesis is a field which has decades of work done already, here's one jumping off point that forms the A and B rings
http://en.wikipedia.org/wiki/Wieland%E2%80%93Miescher_ketone

also cascade-type polycyclization reactions are well developed and you can often get most of the framework in a single step from a linear precursor

this isn't the best example for you but it's in the general area:
http://www.cchem.berkeley.edu/~toste/publications/ja103544p.pdf

similar things have been achieved recently by MacMillan using organocatalysis:
http://www.princeton.edu/chemistry/macmillan/publications/polyene.pdf

and Gange using Pt-based catalysts

You can search some terms like "cationic or cation induced" along with "polycylization", "cascade", and "steroid". I think EJ Corey did this almost 30 years ago using epoxide opening to initiate the cascade.

[Anonymous No.5715709]

>>5715665

>organic chemistry
>possible

Respect to your orgobros for somehow doing this shit.

[Anonymous No.5715710]

>>5715691
[cont.]

here's another nice one for you OP, from Jeff Johnson's lab:
"A Case Study in Biomimetic Total Synthesis: Polyolefin Carbocyclizations to Terpenes and Steroids" (free full text, looks like a review article, all the figures are at the end if you get the pdf)
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2575671/

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2575671/pdf/nihms64854.pdf

[Anonymous No.5715719]

>>5715710
[cont.]
another review, this one by KC Nicolaou
"Cascade Reactions in Total Synthesis"
http://www.rci.rutgers.edu/~layla/mc504/pdfs/cascade_reactions.pdf

[Anonymous No.5715752]

draw a picture of it

[Anonymous No.5715766]

>>5715685
It was assigned a week ago, its due Friday. I spend the last week completing the rest of the assignment... researching the drug, history, use, etc...


>>5715691
The synthesis of steroids.. thank you. very useful. And I'm looking through the other links you included. Thank you!

I think the expoxides are the hardest part!

She won't let me do any enzymatic reactions, it all has to be chemical.

I'll be referring to this thread throughout the night.

Thank you sincerely for all your help.

[Anonymous No.5715782]

>>5715766
>I think the expoxides are the hardest part!
your target doesn't have epoxides, it has cyclopropanes and they are easy to make from alkenes using diiodomethane and Zn metal

http://www.organic-chemistry.org/namedreactions/simmons-smith-reaction.shtm

[Anonymous No.5715826]

I'll think about this for a bit. Gimme like 10 min.

[Anonymous No.5715867]

>>5715826
or like an hour

[Anonymous No.5715882]

>>5715867
fuck it i have my own homework

[Anonymous No.5715904]

look up patents

[Anonymous No.5715921]

>>5715904

Haha I tried this but my synthesis was over 200 steps once I got it down to the simple carbons...

I'll post what I have so far in a second.

[Anonymous No.5715920]

>>5715904
>implying OP's prof isn't familiar with the patent literature

would you give a student credit just for looking it up?

[Anonymous No.5715930]

[Anonymous No.5715934]

>>5715930

This is the level of functionality she expects

"It doesn't have to work in the lab, just on paper."

The point of the assignment is too use our "arsenal" of reactions to build a complex compound.

[Anonymous No.5715942]

>>5715930
If you are going to use a route such as the one you've begun to outline, I would begin with the Wieland-Miescher ketone; that's a well established intermediate there's no reason to back up farther than that. (Does your prof. really expect you to outline a synthesis for benzene or benezesulfonic acid?)

Unfortunately the step you have proposed proceeding from the W-M ketone is not going to work, you've got no leaving group to help you in the desired elimination (meaning that reaction is not balanced, you have not accounted for one H-atom).

[Anonymous No.5715945]

>>5715934
>This is the level of functionality she expects
ok, I didn't update the thread before posting this
>>5715942, but the second paragraph still stands.

[Anonymous No.5715954]

>>5715945

I'm really trying to see this.. The step where I use the (-OH) to remove the hydrogen?

[Anonymous No.5715964]

>>5715954
>The step where I use the (-OH) to remove the hydrogen?
yes, using OH- to remove H would give an anion, right? but you write the product as an alkene of neutral charge

[Anonymous No.5715966]

>>5715964
just to be clear:
... to remove H+

[Solardarity !Se4Solar1M No.5715969]

>>5715665

Short answer: Just throw in some molecules that "could" form into your assigned drug. Functional groups are probably going to be the most important. I'm not sure what your professor wants exactly, does he/ she want an exact process, or wha?

[Anonymous No.5715971]

when I took ochem my proff didn't care much.
I had the same assignment but different compound

[Anonymous No.5715974]

>>5715964
>>5715966
[following up on these earlier posts]
OP what happens when you do the deprotonation you propose? You get a vinylogous enolate.
http://en.wikipedia.org/wiki/Vinylogy

[Anonymous No.5716007]

I see I see... Yes. I'm trying to figure out a way to add a halogen now..

[Anonymous No.5716015]

Maybe bromate the ring with Br2 and UV... Then use KOH to create a double bond.

[Anonymous No.5716047]

>>5716007
>the functional group waltz
yes
IIRC you can do selective protection (cyclic ketalization) or selective reduction of the two ketones; one is next to a quat. center one is not, one is part of an enone one is not so the have different reactivity.

If you can make the ketal of the one in the enone, you can use a Pd-catalyzed oxidation (http://en.wikipedia.org/wiki/Saegusa%E2%80%93Ito_oxidation)) next to the other ketone (to give you another enone) which gives you more functionality in the area you want on the B ring.
see also
http://pubs.acs.org/doi/abs/10.1021/ja206575j

Although the above might be a good approach my gut instinct says to form the C ring first, and then work on functional groups to get to the alkene needed for cyclopropanation.

[Anonymous No.5716493]

[Anonymous No.5716525]

>>5715930

>making benzene from 1,6-dibromohexane

My sides

[Anonymous No.5716528]

>>5715665
>I feel that the moment I react one reagent it will attack the reset of the molecule
this is true. but youre a chemist, you dont need to worry about efficiency. if there are 10 sites for attack you can still get 10% yield for that step. if you have 20 steps, maybe youll get 0.01% yield. but hey, you made the desired molecule, at least SOME of the time. its TECHNICALLY right. let the chemical engineers worry about making it practical

[Anonymous No.5717384]

>>5715665
Just look it up in scifinder and then present that as your own work. This is how most organic chemists operate anyways.

[Anonymous No.5717447]

>3rd year orgchem PhD student reading and cooking everyday
>mfw OP's task

Honestly, I don't know where to start. It's a known compound so google its total synth. I'm sure it's based on standart hormone synthesis through Robinson annelation.