Surfactants with acyl-amino or lipopeptide structure are mild and environmentally friendly and used for example in baby shampoos. However, the technical synthesis relies on the Schotten-Baumann-condensation reaction, which needs acyl chlorides as stoichiometric reagents. Taking into account the “12 Green Principles of Chemistry” we evaluated more sustainable chlorine-free synthesis strategies towards N-acyl amino acids. Promising results were obtained with the coupling-agent T3P for fatty acid activation [1] and with aminoacylase for direct condensation of fatty and amino acid in aqueous environments [2,3]. T3P was classified as a sustainable activating agent for peptide synthesis and recycling is possible by dehydration condensation of the hydrolysed form to the reactive cyclic anhydride. We produced N-acyl amino acids within two hours of reaction time at room temperature in green solvent ethyl acetate and even under solvent-free conditions. Furthermore, the application of T3P allowed a step-by-step activation, which makes tailor-made lipopeptide synthesis possible. Still, the selectivity of the consecutive coupling of two amino acids needs to be optimized. An even greener approach is the direct enzymatic coupling of a fatty acid and an amino acid without the utilization of protective group chemistry or coupling and activating agents. The novel pH- and thermostable recombinant aminoacylase PmAcy from Paraburkholderia monticola was evaluated for its synthesis potential towards N-acyl-amino acids [4]. The enzyme accepted a broad range of fatty acids and amino acids and direct coupling was possible in aqueous environment at substrate concentrations of up to 400 mM. Thus, the enzyme is an interesting alternative to the currently used Schotten-Baumann synthesis.
[1] Basavaprabhu, T. M. Vishwanatha, N. R. Panguluri, V. V. Sureshbabu, Synth 2013, 45, 1569–1601.
[2] Y. Takakura Y. Asano, Biosci Biotechnol Biochem. 2019, 83, 1964–1973.
[3] G. Haeger, J, Wirges, N. Tanzmann, S. Oyen, T. Jolmes, K-E. Jaeger, U. Schörken, J. Bongaerts, P. Siegert, Microb Cell Fact 2023, 22, 77.
[4] G. Haeger, S. Oyen, J. Bongaerts, T. Jolmes, K-E. Jaeger, U. Schörken, P. Siegert, submitted to Appl Microbiol Biotechnol.