Fmoc-a-methyl leucine coupled to Wang resin?

[TheBlob]

Hey guys,

This is my first time posting on these forums, and I don't know if this is the right place for this.

I've already searched scifinder and google, and didn't find anything on the subject, so I hope someone here will have some kind of answer for me!

Has anyone ever coupled Fmoc-alpha-methyl leucine on a Wang resin? If so, under what conditions? I know the amino acid is pretty hindered, so I wouldn't be surprised if this reaction required different conditions than normal amino acids.

Thanks in advance!

[Kunal Pandya]

Fmoc-N-Methyl Leucine (Fmoc-a-methyl leucine) having hinderance on Amino terminal and not much on carboxyl ,So you can couple it to wang resin in similar manner as other amino acid.

Condition is 2Eq amino acid (Fmoc-a-methyl leucine ) + 2Eq HoBt + 2.1 Eq DCC/DIPC and DMAP(Dimethyl amino pyridine).

Equivalent of DMAP you can try between 0.3 eq to 1 eq. As it promote racemization SO you can try different equivalent of DMAP to get your required Substitution.

All equivalents are calculated against the mm of Wang Resin.

Regards
Kunal Pandya

[TheBlob]

Thanks for the advice, but actually I meant alpha methyl, leucine, aka leucine with an extra methyl on the chiral carbon, which means that the carboxylic acid will still be kind of hindered.

[Kunal Pandya]

Sorry for misunderstanding.
Will you already tried the reaction using DMAP ? I hope it have to work.Please let me know


Regards
Kunal Pandya

[TheBlob]

No need to be sorry :P

I asked a colleague of mine and he told me he used the mitsunobu reaction to couple the wang resin to an even more hindered amino acid, I will tell my intern to try this one.

Will tell you if it works, and thanks for the help!

[Kunal Pandya]

I skip to write rection time, please allow to stir minimum 6 hrs

Regards
Kunal pandya