Synthetic studies of ecteinascidin 743 and fennebricin B
Date
2017
Authors
Le, Vy Hoang, author
Williams, Robert M., advisor
Kennan, Alan J., committee member
Finke, Richard G., committee member
Luger, Karolin, committee member
Journal Title
Journal ISSN
Volume Title
Abstract
Ecteinascidin 743 (Et-743, trabectidin or Yondelis®) possesses an impressive antitumor activity that it was approved for treatments of several cancer types worldwide. Since this natural product only presents as a trace amount in the nature, the main supply of this drug for research and commercial use is from laboratory synthesis. Many syntheses of Et-743 have been reported including three total syntheses, two formal syntheses and two semisyntheses. The biological activities of fennebricin B were unknown due to the scarcity of this natural product. However, fennebricin B share a common pentacyclic core with Et-743, thus may also possess interesting biological activities. Our group completed our formal synthesis of the natural product in 2008, featuring the Pictet-Spengler reaction to construct the pentacyclic core of Et-743. Our work, however, also produced both desired and undesired pentacycle without selectivity. We herein described an improved formal synthesis of Et-743 employing bromine auxiliary to generate the pentacylic core of Et-743 with the desired regioisomer as the only product. This approach was also utilized in the synthetic studies toward the total synthesis of fennebricin B.