[diablo]

Hi folks,

i need your help if you're familiar with organic chemistry

look at following picture:



You see a FMOC group which is linked to an aminoacid via Carbamatebondage .

my question is: i want to subsitute the FMOC by attacking the COO-group.... --> the aim is that some other moiety is sticked on the aminoacid at the same place where the FMOC was .

I hope you understood my question and maybe you can help me

thx & Greets
Diablooo

[lutesium]

Can you open your question a little bit more please??? Because its really hard to understand what you're asking!!!


Lutesium!!!

[sjh9]

If I understand you correctly you'd like a nucleophile to attack the C=O center kicking out 9-Fluorenemethanol and replacing it with something else.  The problem with this approach is that the methylene protons are acidic and a nucleophile will probably remove one of them first resulting in deprotection and CO2 liberation.

[diablo]

yes, sjh9 you're right- thats what i want...

today i thought about transesterification... would this be a solution ?

greets
Diablooo

[alphahydroxy]

What are you actually wanting to put in place of the Fmoc protection? I'm not sure I've come across a good method of attacking the carbamate carbon with a nucleophile - it would probably be easier to deprotect the nitrogen and react the free amine with an appropriate acid using standard amide coupling procedures...

[diablo]

the real problem is actually more complex: i got a peptide where fmoc is random linked at some aminoacids, and i want to detect those aminoacids (with ms) ... --> now the problem is that the fmoc is not only fmoc (it has some other moiety on it which varies in mass...) so i want to "kick" the whole fmoc and substitue it with some moiety with "constant" mass... --> hope you undstand it now

Another idea came up: Could i take the peptide, add Boc ( to protect ALL the other free NH2 groups) , then "kick" the FMOC i don't want and add some "normal" Fmoc, which binds to the free NH2 groups ? --> do you think this could work or it's just a dream ?^^

greets
Diabloooo

[sjh9]

Another idea came up: Could i take the peptide, add Boc ( to protect ALL the other free NH2 groups) , then "kick" the FMOC i don't want and add some "normal" Fmoc, which binds to the free NH2 groups ? --> do you think this could work or it's just a dream ?^^

Seems plausible, make sure to use a base that won't remove your FMOC group when installing the boc group (DIPEA).

[diablo]

thx for your help

So in theory i could mix BOC2O + DIPEA + Peptides and hope for "BOC-ylating".

But how do you know that DIPEA won't remove FMOC and how do you know that BOC20 works with DIPEA ( do you know any paper or source where i can read this ?^^)

thx,
diabloo

edit: i just read that DIPEA is a good base, but poor nucleophile...(
source: http://en.wikipedia.org/wiki/Diisopropylethylamine..and FMOC is kicked by nucleophiles....
but still i don't have any idea how much (g/ml) Boc,DIPEA i should add to my peptide solution...)

[sjh9]

but still i don't have any idea how much (g/ml) Boc,DIPEA i should add to my peptide solution...)

What solvent are you using for this process? (DMF?).  I suggest you add (Boc)2 in small portions and monitor the progress by the Kaiser test.  When your reaction mixture no longer tests positive, you have protected all your free amines.  The nice thing about (Boc)2 is that the side products can be removed under vacuum (t-buOH, excess DIPEA).  If you have unreacted (Boc)2 it will decompose aftera little while if you add water to your reaction mixture.  The process would be a lot easier if you could immobilize your peptide on solid support, but this isn't always possible.

[diablo]

but still i don't have any idea how much (g/ml) Boc,DIPEA i should add to my peptide solution...)

What solvent are you using for this process? (DMF?).  I suggest you add (Boc)2 in small portions and monitor the progress by the Kaiser test.  When your reaction mixture no longer tests positive, you have protected all your free amines.  The nice thing about (Boc)2 is that the side products can be removed under vacuum (t-buOH, excess DIPEA).  If you have unreacted (Boc)2 it will decompose aftera little while if you add water to your reaction mixture.  The process would be a lot easier if you could immobilize your peptide on solid support, but this isn't always possible.

what do you mean with solvent? --> i thought i can just add the BOC2O+ Base (DIPEA) to my peptide solution and thats it

greets
Diabloo

P.S. or in general, do you think another protecting group would be better in this situation ( than BOC)

[sjh9]

what do you mean with solvent? --> i thought i can just add the BOC2O+ Base (DIPEA) to my peptide solution and thats it
greets
Diabloo
P.S. or in general, do you think another protecting group would be better in this situation ( than BOC)

If your peptide is water (or protic solvent) you may have trouble introducing the boc group as boc anhydride can hydrolyze.  Peptide synthesis is often performed in DMF.

[diablo]

Ok, thx i'll check it out  (will test with /without water etc with a test-peptide...)

greets Diabloo

Edit: solvent will be DMSO ( hope that works as well )