## 1 Introduction  
The demands to develop green and sustainable synthetic methods in the field of fine chemicals, combined with regulatory pressure to produce these substances efficiently and safely, are increasing. The toxic and volatile nature of organic solvents poses a serious environmental threat [1]. Thus, the redesign of chemical processes to avoid hazardous organic solvents is highly desirable [2; 3; 4]. In recent years, there has been increased demand for the chemical synthesis of peptides for use in a wide variety of applications because of the explosive growth in biological research related to these molecules.  
However, chemical peptide syntheses consume extremely large quantities of organic solvent due to the multiple solvent-based condensation steps. Hence, there is a compelling need for new peptide synthesis technologies which do not damage the environment, and so there is increased focus on organic solvent-free methods of peptide synthesis using environmentally friendly solvents, such as water [5; 6; 7; 8; 9; 10; 11].  
Water-based peptide synthesis remained unexplored for a long period, because the most common peptide building blocks, _t_-butyloxycarbonyl (Boc)- and 9-fluorenylmethoxycarbonyl (Fmoc)-amino acids [12; 13], are sparingly soluble in water. We recently reported aqueous peptide synthesis methods which utilize water-dispersible Boc- and Fmoc-amino acids nanoparticles [9; 10; 11]. This technology uses suspended nanoparticle reactants for the coupling reaction to overcome the solubility problem and offers many advantages in terms of reaction efficiency.  
The use of non-conventional energy sources, _viz._ microwave (MW) irradiation has become a preferred choice for the organic chemist [1; 14; 15; 16]. There are many examples of the application of MW irradiation in peptide synthesis, including automated peptide synthesizers equipped with MW capability [17; 18; 19; 20; 21; 22]. The main advantages of MW-assisted chemistry are shorter reaction times and higher yields. These dramatic effects are caused by the unique heating profiles of MW irradiation. Unlike conventional heating, MW energy activates any molecule with a dipole moment, resulting in rapid heating. Indeed, the excellent dielectric properties of water offers significant advantages when used as a solvent in MW assisted reactions. The Boc strategy is well known to be suitable for industrial  
Figure 1: Aqueous microwave (MW)-assisted solid-phase synthesis using Boc-amino acid nanoparticles.  
chemistry and green chemistry, because only gases are generated, without any other by-products produced by de-protection of the Boc group. Gases require less disposal energy than do solid wastes generated by de-protection of other protecting groups such as the Fmoc group. The trial of MW assisted water-based peptide synthesis using non-dispersed Boc-amino acids has been reported previously [23]. In this case, 2 reaction cycles were necessary to achieve complete coupling, requiring a total reaction time of over 15 min. This reaction rate was slow compared to general peptide synthesis in ordinary organic solvents with MW irradiation. With this in mind, we present here a water-based solid-phase synthesis using water-dispersible Boc-amino acid nanoparticles in combination with microwave irradiation aimed at reducing reaction time and increasing reaction yield (Figure 1).