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Synthesis 2026; 58(01): 67-71
DOI: 10.1055/a-2695-8576
Paper

A Chlorine-Bearing Asymmetric Center as a Stereocontrol Element in a Short Formal Synthesis of Steviol

Autor*innen

  • Sharon E. Michalak

    1   Department of Chemistry, 1102 Natural Sciences II, University of California, Irvine, CA 92697, USA

  • Christopher D. Vanderwal 

    1   Department of Chemistry, 1102 Natural Sciences II, University of California, Irvine, CA 92697, USA
    2   Department of Pharmaceutical Sciences, 856 Health Sciences Road, Suite 5400, University of California, Irvine, CA 92697, USA

We thank the NIH for support of this work through grants R01-GM129264 and R35-GM145252. S. E. M. was partially supported by an Allergan Graduate Fellowship.
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Graphical Abstract

Abstract

Steviol is one of the myriad polycyclic terpenoids bearing oxygenation on the axially disposed C19 carbon. The presence of this C19 alcohol renders the C4 quaternary carbon stereogenic, issuing a challenge for stereoselective synthesis. Here we show that a suitably disposed chlorine atom at C2, coupled with the correct diastereomer of terminal epoxide that initiates cationic bicyclization, leads to the desired stereochemical outcome. Subsequently, the anisole terminating group undergoes Birch reduction that simultaneously reduces the C–Cl bond, removing the transient “auxiliary” and completing a short, highly stereoselective formal synthesis of steviol. This work provides another example of the power of removable C–X bonds for stereocontrolled synthesis.

Keywords

Cyclizations - Chlorine - Epoxide - Terpenoids - Total synthesis - Stereoselectivity

Supplementary Material



Publikationsverlauf

Eingereicht: 01. August 2025

Angenommen nach Revision: 04. September 2025

Accepted Manuscript online:
04. September 2025

Artikel online veröffentlicht:
21. Oktober 2025

© 2025. Thieme. All rights reserved.

Georg Thieme Verlag KG
Oswald-Hesse-Straße 50, 70469 Stuttgart, Germany

 

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