Total Synthesis of GKK1032A2 via Direct 13-Membered Macrocyclization Using a Nucleophilic Aromatic Substitution of an (η6 -Arene)Chromium Complex.

The first enantioselective total synthesis of GKK1032A2 has been achieved. The key step is a direct construction of the highly strained 13-membered macrocycle of GKK1032A2 by an intramolecular nucleophilic aromatic substitution (SN Ar) reaction. This is the first successful example of construction of a macrocycle with an aryl ether linkage utilizing an intramolecular SN Ar reaction of an (η6 -arene)chromium complex.

The first synthesis and antifungal activities of 9-methoxystrobilurin-type beta-substituted beta-methoxyacrylate.

The first synthesis of 9-methoxystrobilurin-type beta-substituted MOAs was successfully achieved. A chiral oudemansin-type beta-substituted MOA was also synthesized utilizing Mukaiyama's asymmetric aldol reaction. Antifungal activities of the synthesized compounds against several representative fungi were examined by disk-diffusion assay. As a result, unique and superior antifungal properties of 9-methoxystrobilurin-type beta-substituted MOAs compared with those of oudemansin-type analogue were clearly revealed.

Remarkable influence of the aromatic substructure in 9-methoxystrobilurin derivatives on their antifungal activity.

9-Methoxystrobilurin-type beta-methoxyacrylate antibiotics (MOSBs) having various aromatic substructures were synthesized. The antifungal activity of the synthesized MOSBs against pathogenic and non-pathogenic fungi was examined, and the obtained results revealed that the antifungal activity of MOSBs was highly dependent on the aromatic substructures. However, no significant correlation was observed between cytotoxicity against human fibroblasts-like cell line and their structural properties. In addition, our results suggested that the strong growth-inhibitory activity of 9-methoxystrobilurin K against human-derived cell lines should be related to its hindered ether-type substructure.