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A Customizable Approach for the Enzymatic Production and Purification of Diterpenoid Natural Products
Published on: October 4, 2019
A unified approach to highly functionalized clovane-type terpenoids: enantiocontrolled total synthesis of
Daigo Ninomiya1, Shota Nagasawa1, Yoshiharu Iwabuchi1
1Graduate School of Pharmaceutical Sciences, Tohoku University 6-3 Aoba, Aramaki, Aoba-ku Sendai 980-8578 Japan shota.nagasawa.d8@tohoku.ac.jp y-iwabuchi@tohoku.ac.jp.
Abstract:
This study presents an enantioselective collective total synthesis of the highly functionalized clovane-type terpenoids rumphellclovane E (4) and, sarinfacetamides A (5) and B (6). An efficient enantio-controlled, second-generation route to an originally designed versatile intermediate (12/ent-12) enables the collective synthesis, including the first total synthesis of sarinfacetamides A (5) and B (6). The rapid assembly of the bicyclo[3.3.1]nonane core via a domino Michael-aldol reaction employing a novel acrolein surrogate under basic conditions enabled access to this key intermediate, requiring only five steps from (+) or (-)-dihydrocarvone (18/ent-18). We further demonstrated the versatility of this strategy through the synthesis of a structural analogue containing a furan moiety. Given the diverse biosynthetic origins of clovanes, which arise from caryophyllene or xeniaphyllane terpenoids, this synthetic strategy may prove applicable to a broader range of clovane-type terpenoids.
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