14-step synthesis of (+)-ingenol from (+)-3-carene.

نویسندگان

  • Lars Jørgensen
  • Steven J McKerrall
  • Christian A Kuttruff
  • Felix Ungeheuer
  • Jakob Felding
  • Phil S Baran
چکیده

Ingenol is a diterpenoid with unique architecture and has derivatives possessing important anticancer activity, including the recently Food and Drug Administration-approved Picato, a first-in-class drug for the treatment of the precancerous skin condition actinic keratosis. Currently, that compound is sourced inefficiently from Euphorbia peplus. Here, we detail an efficient, highly stereocontrolled synthesis of (+)-ingenol proceeding in only 14 steps from inexpensive (+)-3-carene and using a two-phase design. This synthesis will allow for the creation of fully synthetic analogs of bioactive ingenanes to address pharmacological limitations and provides a strategic blueprint for chemical production. These results validate two-phase terpene total synthesis as not only an academic curiosity but also a viable alternative to isolation or bioengineering for the efficient preparation of polyoxygenated terpenoids at the limits of chemical complexity.

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عنوان ژورنال:
  • Science

دوره 341 6148  شماره 

صفحات  -

تاریخ انتشار 2013