A a continuous, solvent-free and non-enzymatic method for synthesizing a compound of formula (I) : Ra-POLYPEP-Rc (I) wherein : POLYPEP is a poly-amino acid compound, Ra means a N-protective group; Rc means-O-Rd, wherein Rd means a hydrogen atom, a (C1-C24 alkyl) group, a methyl group substituted with one or more phenyl groups, a non-substituted (C6-C10) aryl group, a O-protective group or a -NReRf group wherein Re and Rf groups mean, one independently of each other, a hydrogen atom, a (C1-C24) alkyl group, a methyl group substituted with one or more phenyl groups, a non-substituted (C6-C10 aryl) group or a N-protective group, which method comprises the steps of: a) feeding an extrusion reactor with a compound of formula (II) Ra-PEPNt-Rg (II) wherein; PEPNt is a mono- or a poly-aminoacid compound, Ra is as defined for the compound of formula (I), and Rg is a leaving group and a compound of formula (III) H-PEPCt-Rc (III) wherein : PEPCt is a mono- or a poly-amino acid compound, and Rc is as defined for the compound of formula (I) in the absence of any solvent, so that the compound of formula (II) and the compound of formula (III) react together for generating a compound of formula (I), and b) collecting the compound of formula (I) from the extrusion reactor. POLYPEP is a poly-amino acid compound, Ra means a N-protective group; Rc means-O-Rd, wherein Rd means a hydrogen atom, a (C1-C24 alkyl) group, a methyl group substituted with one or more phenyl groups, a non-substituted (C6-C10) aryl group, a O-protective group or a -NReRf group wherein Re and Rf groups mean, one independently of each other, a hydrogen atom, a (C1-C24) alkyl group, a methyl group substituted with one or more phenyl groups, a non-substituted (C6-C10 aryl) group or a N-protective group, which method comprises the steps of: a) feeding an extrusion reactor with a compound of formula (II) Ra-PEPNt-Rg (II) wherein; PEPNt is a mono- or a poly-aminoacid compound, Ra is as defined for the compound of formula (I), and Rg is a leaving group and a compound of formula (III) H-PEPCt-Rc (III) wherein : PEPCt is a mono- or a poly-amino acid compound, and Rc is as defined for the compound of formula (I) in the absence of any solvent, so that the compound of formula (II) and the compound of formula (III) react together for generating a compound of formula (I), and b) collecting the compound of formula (I) from the extrusion reactor. a) feeding an extrusion reactor with a compound of formula (II) Ra-PEPNt-Rg (II) wherein; PEPNt is a mono- or a poly-aminoacid compound, Ra is as defined for the compound of formula (I), and Rg is a leaving group and a compound of formula (III) H-PEPCt-Rc (III) wherein : PEPCt is a mono- or a poly-amino acid compound, and Rc is as defined for the compound of formula (I) in the absence of any solvent, so that the compound of formula (II) and the compound of formula (III) react together for generating a compound of formula (I), and a compound of formula (II) Ra-PEPNt-Rg (II) wherein; PEPNt is a mono- or a poly-aminoacid compound, Ra is as defined for the compound of formula (I), and Rg is a leaving group and PEPNt is a mono- or a poly-aminoacid compound, Ra is as defined for the compound of formula (I), and Rg is a leaving group and a compound of formula (III) H-PEPCt-Rc (III) wherein : PEPCt is a mono- or a poly-amino acid compound, and Rc is as defined for the compound of formula (I) in the absence of any solvent, so that the compound of formula (II) and the compound of formula (III) react together for generating a compound of formula (I), and PEPCt is a mono- or a poly-amino acid compound, and Rc is as defined for the compound of formula (I) in the absence of any solvent, so that the compound of formula (II) and the compound of formula (III) react together for generating a compound of formula (I), and b) collecting the compound of formula (I) from the extrusion reactor. <EOS>