1. Synthesis of New Cyclopeptide Analogues of the Miuraenamides
Sarah Kappler, Andreas Siebert, Uli Kazmaier Curr Org Synth. 2021;18(4):418-424.doi: 10.2174/1570179418666210113161550.
Introduction:Miuraenamides belong to natural marine compounds with interesting biological properties.Materials and methods:Miuraenamides initiate polymerization of monomeric actin and therefore show high cytotoxicity by influencing the cytoskeleton. New derivatives of the miuraenamides have been synthesized containing an N-methylated amide bond instead of the more easily hydrolysable ester in the natural products. Results:Incorporation of an aromatic side chain onto the C-terminal amino acid of the tripeptide fragment also led to highly active new miuraenamides.Conclusion:In this study, we showed that the ester bond of the natural product miuraenamide can be replaced by an N-methyl amide. The yields in the cyclization step were high and generally much better than with the corresponding esters. On the other hand, the biological activity of the new amide analogs was lower compared to the natural products, but the activity could significantly be increased by incorporation of a p-nitrophenyl group at the C-terminus of the peptide fragment.
2. Second-generation probes for biosynthetic intermediate capture: towards a comprehensive profiling of polyketide assembly
Ina Wilkening, Silvia Gazzola, Elena Riva, James S Parascandolo, Lijiang Song, Manuela Tosin Chem Commun (Camb). 2016 Aug 16;52(68):10392-5.doi: 10.1039/c6cc04681a.
Malonyl carba(dethia) N-decanoyl cysteamine methyl esters and novel acetoxymethyl esters were utilised as second-generation probes for polyketide intermediate capture. The use of these tools in vivo led to the characterisation of an almost complete set of biosynthetic intermediates from a modular assembly line, providing a first kinetic overview of intermediate processing leading to complex natural product formation.
