Abstract
We accomplished the solid-phase total synthesis of malformin C, which is adaptable for the easy preparation of various derivatives. A solid-phase total synthesis of malformin C was achieved by on-resin macrolactamization and disulfide bond formation, with concurrent cleavage from the resin. Antimalarial and antitrypanosomal activities were examined, which helped elucidate partial structure–activity relationships. Results indicate that the disulfide bond is essential and branched amino acids are also crucial components if the compound is to exhibit potent antimalarial and antitrypanosomal properties.
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Acknowledgements
This work was supported in part by funds from the Drugs for Neglected Diseases initiative (DNDi); a grant for the All Kitasato Project Study (AKPS); and by the 21st Century COE Program, Ministry of Education, Culture, Sports, Science and Technology. We also thank Ms A Nakagawa, Dr K Nagai and Ms N Sato (School of Pharmaceutical Sciences, Kitasato University) for the various instrumental analyses.
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Kojima, Y., Sunazuka, T., Nagai, K. et al. Solid-phase synthesis and biological activity of malformin C and its derivatives. J Antibiot 62, 681–686 (2009). https://doi.org/10.1038/ja.2009.100
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DOI: https://doi.org/10.1038/ja.2009.100
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