Total Synthesis of Taxol Enabled by Inter‐ and Intramolecular Radical Coupling Reactions

Author:

Imamura Yusuke1,Takaoka Kyohei1,Komori Yuma1,Nagatomo Masanori1,Inoue Masayuki1ORCID

Affiliation:

1. Graduate School of Pharmaceutical Sciences The University of Tokyo 7-3-1 Hongo Bunkyo-ku, Tokyo 113-0033 Japan

Abstract

AbstractTaxol is a clinically used drug for the treatment of various types of cancers. Its 6/8/6/4‐membered ring (ABCD‐ring) system is substituted by eight oxygen functional groups and flanked by four acyl groups, including a β‐amino acid side chain. Here we report a 34‐step total synthesis of this unusually oxygenated and intricately fused structure. Inter‐ and intramolecular radical coupling reactions connected the A‐ and C‐ring fragments and cyclized the B‐ring, respectively. Functional groups of the A‐ and C‐rings were then efficiently decorated by employing newly developed chemo‐, regio‐, and stereoselective reactions. Finally, construction of the D‐ring and conjugation with the β‐amino acid delivered taxol. The powerful coupling reactions and functional group manipulations implemented in the present synthesis provide new valuable information for designing multistep target‐oriented syntheses of diverse bioactive natural products.

Funder

Japan Society for the Promotion of Science

Ministry of Education, Culture, Sports, Science and Technology

Publisher

Wiley

Subject

General Medicine

Reference103 articles.

1.  

2.  

3. G. I. Georg T. T. Chen I. Ojima D. M. Vyas ACS Symposium Series 583 American Chemical Society Washington DC 1994;

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