9-methoxystrobilurin K

Uchiro, H., K. Nagasawa, Y. Aiba, T. Kotake, D. Hasegawa & S. Kobayashi. 2001. Asymmetric total synthesis of 9-methoxystrobilurin K. Tetrahedron Letters. 42:4531-4534.

Online source: ScienceDirect

Reviewed by Amy Kruchowski and Christina Richter

9-methoxystrobilurin K was originally found in a mycelial culture of forest fungi. It was noted that the isolated substance exhibited antifungal characteristics to invading organisms by preventing mitochondrial respiration and killing the cell. Naturally occuring 9-methoxystrobilurin displays characteristics of beta-methoxyacrylate antibiotics (MOAs) and in small concentrations has been shown to stop the growth of tumor cells without killing them. Ideally, treatment by such an agent could be an alternative to chemotherapy for cancer patients. But 9-methoxystrobilurin K would not reduce the size of the tumor and surgery may still be necessary. It is not yet known what effects large concentrations of 9-methoxystrobilurin may have on living cells.

Retrosynthetic Scheme:

Highlights of the Retrosynthesis:

The synthesis was centralized around a Heck reaction, which is the coupling of an organic bromide and an alkene with the use of a palladium catalyst. The Heck reaction is one method of extending an organic chain. The first major reaction in the synthesis of 9-methoxystrobilurin K produced an optically active chiral epoxy phenol which was the analogue to the desired 7-bromo-1,5-benzodioxepin-3-ol. The previous bromo alcohol was coupled with an alkene to form an ester. The processes of hydrolyzation and treatment by a hindered base followed by double methylation produced the desired 9-methoxystrobilurin compound along with two other undesired products. Attempts made to irradiate the final products yielded a total of 41% 9-methoxystrobilurin.

H. Uchiro et al. chose to use the Sharpless asymmetric epoxidation reaction to form the desired chiral epoxy because of the reaction's high yield. The asymmetric epoxidation reaction successfully converted 85% of the prenyl alcohol to epoxy phenol.

Christina located the article and typed up the report. Amy got the report approved, created, and attached all compound structures and the retrosynthesis. Together, we edited the report and sought to understand the article, and the purpose of the complex.