[Show abstract][Hide abstract] 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.Keywords: antimalarial activity, antitrypanosomal activity, cyclic pentapeptide, disulfide bond, malformins, solid-phase synthesis
The Journal of Antibiotics 10/2009; 62(12):681-686. DOI:10.1038/ja.2009.100 · 1.73 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
[Show abstract][Hide abstract] ABSTRACT: This article describes the determination of the absolute configurations of the guadinomines, which are novel cyclic guanidyl natural products that are inhibitors of the type III secretion system (TTSS) of bacteria. Any compound that interrupts the TTSS of bacteria is potentially an ideal anti-infectious drug. The reliable asymmetric synthesis of guadinomines has revealed their absolute configurations, which could not have been defined without this synthetic approach. Our report not only describes the asymmetric total synthesis of the title compounds, but also demonstrates the novel concise synthesis of tri-substituted piperazinone cores as optically pure forms. The novel feature of our method is an intramolecular S(N)2 cyclization that uses PPh(3) and I(2) to construct the unique 5-membered cyclic guanidine substructure.
[Show abstract][Hide abstract] ABSTRACT: Total synthesis of a fungal cyclic peptide, malformin C, recently rediscovered as a G2 checkpoint inhibitor was completed. Our synthesis involved a convergent approach with respect to a linear pentapeptide, cyclization, and oxidative disulfide formation.
The Journal of Antibiotics 05/2008; 61(5):297-302. DOI:10.1038/ja.2008.42 · 1.73 Impact Factor