Aqueous Microwave-Assisted Solid-Phase Synthesis Using Boc-Amino Acid Nanoparticles

Abstract

Abstract:We have previously developed water-based microwave (MW)-assisted peptide synthesis using Fmoc-amino acid nanopaticles. It is an organic solvent-free, environmentally friendly method for peptide synthesis. Here we describe water-based MW-assisted solid-phase synthesis using Boc-amino acid nanoparticles. The microwave irradiation allowed rapid solid-phase reaction of nanoparticle reactants on the resin in water. We also demonstrated the syntheses of Leu-enkephalin, Tyr-Gly-Gly-Phe-Leu-OH, and difficult sequence model peptide, Val-Ala-Val-Ala-Gly-OH, using our water-based MW-assisted protocol with Boc-amino acid nanoparticles.

Greening Fmoc/tBu solid-phase peptide synthesis

“…However, in this case, and after testing several coupling reagents, they found that DMTMM with NMM was the best combination [166,167]. They successfully synthesized Leu-Enkephalin using nanodispersed Boc-amino acids [168]. Of note, these authors has also demonstrated that the aqueous microwave-assisted paradigm renders lower epimerization in comparison to the common paradigm with organic solvents.…”

Green solvents for the formation of amide linkages

“…Hojo's group made a significant contribution to the development of greener protocols for SPPS in water. 84 In this regard, in 2013, Hojo et al described a water-based solid-phase synthesis using Boc-amino acid nanoparticles, 85 previously applied by the same group to Fmoc-amino acid nanoparticles. 86 The reactions were performed using 4-(4,6dimethoxy [1,3,5]triazin-2-yl)-4-methyl-morpholinium chloride (DMTMM) as the coupling reagent, HMBA-PEG (hexamethylenebisacetamide-polyethylenglycole) grafted resin as the support and microwave radiation as the non-conventional energy source set to a power of 70 W (70 °C).…”

Green Transformation of Solid-Phase Peptide Synthesis

“…In theory, nanoparticles have a higher surface area, which leads to increased homogeneous mixing of these particles with the resin in water, thus allowing a smooth progression of the reaction. , The nanoparticles were prepared using a planetary ball mill in the presence of PEG as a dispersion agent. TFA and 0.1 N NaOH 90% aqueous EtOH were used as deprotection solution for the Boc and Fmoc strategy, respectively. Again, PEG-grafted resin, Triton X-100 solution for washing, and microwave heating were also used in the synthesis of various peptides, including Leu-enkephalin, dermorphinamide, and ACP (65–74). ,− This strategy shows that the use of the commercial Boc and Fmoc amino acids has the major advantage of achieving acceptable yields.…”