[kriggy]

Hi there, we got an assignment for class where we are to synthesise (on paper) tetrapeptide using solid phase technique using different immobilization techniques: via a) C-terminus b) N-terminus c) backbone imobilization d) immobilization via side chain of AA. The assignment is more about choice of protecting groups and linker than about the specific conditions of reactions since the peptide couplings are rather well developed. Anyway, this is my attempt on C-terminus immobilization way (Im using Wang resin):

I have some questions: is actualy possible to cleave all the protecing groups in the last step by trifluoracetic acid? They should be acid labile but I just want to be sure. I suppose some radical scavenger should be used to get rid of the tert-butyl and trityl radicals right?

And considering the immobilization via N-terminus? what protecting groups are used for carboxylic acid to block the self-condensation reaction in the peptide coupling? Or could it be done without COOH protection ? For example¨: to the free COOH bounded on resin, add DIC, HOBT, DMAP, form the reactive ester and then wash the excess out and add aminoacid that is not protected at C-terminus?

Thank you guys

[phth]

Look up info about SPPS in a microwave.  Trt will go first, then tBu, then Boc, so you may need to heat.  Personally I would prefer to work with 4-6N HCl in dioxane to deprotect, but it really doesn't matter.  Why would the yield be lower compared to homogeneous phase synthesis?  You will need to put a cation quencher in there if you want the phenol to survive the TFA deprotection quantitatively.

[phth]

Examples of quenchers would be triethylsilane or excess of phenol.