Synthetic study of andrastins: stereoselective construction of the BCD-ring system

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Abstract

Andrastins are meroterpenes isolated from Penicillium sp. FO-3929 that display highly potent inhibitory activities toward protein farnesyltransferase. Structurally, they possess a unique steroidal tetracyclic skeleton (the ABCD-ring) with three contiguous quaternary stereocenters on the C-ring. Herein, we describe our nitrile cyclization-based approach to the stereoselective construction of the BCD-ring system of andrastins, which contains three contiguous quaternary stereocenters on the C-ring and the correct oxidation states of the D-ring.

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Acknowledgements

We acknowledge Dr. Eri Fukushi and Mr. Yusuke Takata (GC-MS & NMR Laboratory, Faculty of Agriculture, Hokkaido University) for their mass spectral measurements. TA is a Research Fellow of the Japan Society for the Promotion of Science (JSPS). This work was supported by JSPS KAKENHI Grant Numbers JP15K01795, JP18K05339, JP18H01970, and JP15H05842 in Middle Molecular Strategy.

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Correspondence to Fumihiko Yoshimura or Keiji Tanino.

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Dedication: Dedicated with respect to Professor Samuel J. Danishefsky for his outstanding contributions to natural products synthesis.

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Yoshimura, F., Abe, T., Ishioka, Y. et al. Synthetic study of andrastins: stereoselective construction of the BCD-ring system. J Antibiot 72, 384–388 (2019) doi:10.1038/s41429-018-0136-x

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