For solid phase peptide synthesis which solvent is better? I have used DCM, DMF and NMP. which is a given efficient coupling? And the reason for this is PS-TPGD, Merifield Resin and Rinkamide resin normally am using.
NMP is best for SPPS., i will give great solvation and its function will somewhat disturb aggregation during the synthesis. DMF, NMP and DMSO are mostly using for SPPS.,
DMF is better for amino acid coupling reaction. As most resins swell in DMF so that the more surface area (more functional group ) would be available for bonding.
After reaction you can remove DMF by filtration and washing the residue with Methanol and DCM at least twice.
polar protic or aprotic solvents which makes your substrate soluble.general people are using Methanol, DMF, DMSO same as arun, saraniya and madhukar has suggested.
NMP - Nmethylpyrolidone is very best for SPPS, its giving more swelling and solvation in all condition., DMSO and DMF is second preference, DCM is not good option for SPPS.,
DMF is commonly used, sometimes in combination with DCM (some polystyrene based resins swell better in DCM, but these days DMF alone is just fine- most of the resins are peg- polystyrene type) . You must however use high quality
DMF is most commonly used because it dissolves reactants, on one side, and swells well the modern resins. In the old days we had to pre-swell polystyrene resins in DCM before adding DMF-dissolved components. NMP dissolves some protected amino acids better, but at the same time more viscous and costly. ACN can be used but again it is more expensive and importantly more volatile (big disadvantage for long synthesis) - may induce crystallization and clog synthesizer tubes (especially if nitrogen is used to agitate the resin) e.t.c. The short answer is DMF#1 (cheap, non-volatile, dissolves reactants, swells resins), but needs to be fresh (fee of DMA) NMP#2 (occasionally, sometimes in combination with DMF - more stable, but also more viscous and costly), ACN#3 - for quick manual couplings (without N2 bubbling), DCM - almost never these days (for coupling I mean). Occasionally I used pyridine or benzene for coupling of unnatural hydrophobic AA, but again, all depends on what you r doing.
Hi. You need a non-nucleophilic solvent for AA coupling. Methanol will react with your activated AA to form a methyl ester. Solubility of some derivatives can be an issue. For moderately soluble derivatives you can still try to use more solvent and increase the coupling time and the number of couplings. Also some derivatives may dissolve much better after you add the coupling agent (ex. DIC/HOBt) and convert it to the corresponding active ester. Because of the solubility issues some derivatives can not be coupled automatically. You have to stop the synthesizer sequence, manually couple the "nasty" residue , and restart the automatic synthesis from N+1 AA. I also suspect that because your unnatural AA readily dissolves in methanol that you have some unprotected OH-groups in your derivative? Protection of the OH groups will improve the solubility in DMF and NMP. Additionally, incorporation of derivatives containing unprotected OH-groups will result in branching of your peptide during subsequent couplings. Basically, make sure that the derivative that you intend to couple is compatible with Fmoc SPPS procedures. Hope it helps!