[inthewasher]

Hello everyone, I am an incoming freshman at a state university, and am planing on majoring in organic chemistry. My background is somewhat limited, with only the standard inorganic high school curriculum, and a few alkaloid extractions under my belt.

I am curious as to where i should start in regards to the isolation of mitragynine from kratom leaf, and the subsequent conversion of it to the more active 7-Hydroxymitragynine.  I plan on studying the therapeutic potential of of this compound, which is reputed to be much more potent than morphine, but with less addiction and tolerance potential because of its affinity to other receptor groups, most notably as an alpha-2 adrenergic antagonist. Any help would be greatly appreciated. My attempt to use a weak solution of sodium hydroxide merely turned the compound into a freebase, instead of adding a hydroxy group like I hoped. What other compounds should I try, and would this be a one step or multi step reaction?

Wikipedia has the basic chemical structures of the compounds;

http://en.wikipedia.org/wiki/Mitragynine
http://en.wikipedia.org/wiki/7-hydroxymitragynine

As you can see the only difference between the compounds is an -OH attached to the 7th carbon atom.

I feel so stupid that I cant figure out how to attach a hydroxyl group there, I have much to learn this year.

[phil81]

Try these conditions: 1 eq. TFA, mCPBA

Why will it work and what's the mechanism?

[inthewasher]

Alright, the triflouroacetic acid is used to create a sufficiently acidic environment for the meta-Chloroperoxybenzoic acid to donate its hydroxyl group, specifically at the 7th carbon because of its shape. Does that sound right?

My subsequent frantic google search to figure out what you were talking about showed me how little I know about chemistry, and I don't want to be a psychic vampire letting you all do all the thinking for me. I want to figure out and understand the methodology you used to come up with that, so that I may be able to do it myself. I plan on buying a good chemistry book as a result.

Btw thanks for the response.

[phil81]

My pleasure ;-)

- What kind of reaction are peracids usually used for? Can this happen here?
- Maybe ignore the TFA for the moment, it plays a secondary role.

If you have access to literature about indole chemistry, you should find the solution without a problem.

[inthewasher]

From more information gathered on the internet (the best resource I have until the organic chemistry book comes) I see that peracids are used in good 'ole oxidation reactions. Also I found out that indoles are easily oxidized "given their electron-rich nature". This means an oxidation reaction should easily occur in mitragynine, which is an indole alkaloid. Once this oxidation occurs I assume the oxygen double bonded to the carbon (hopefully at the 7th carbon) will seek out a free hydrogen atom provided by an acidic environment

I'm curious as to what prevents the mCPBA from oxidizing other parts of the mitragynine molecule. Will it only oxidize at the 7th carbon, and what does TFA do other than provide an acidic environment (if it does anything else)?

It's more important to know whats going on than to just make it happen so I thank you for the questions :-)

[phil81]

You're on the right track. To give you another clue, peracids are usually used for epoxidation. Where could you form an epoxide, and what could happen then?

Concerning TFA: It will protonate the most basic site in the molecule (which?). This is necessary to prevent a side reaction with mCPBA.