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DOI: 10.1055/a-2695-8576
A Chlorine-Bearing Asymmetric Center as a Stereocontrol Element in a Short Formal Synthesis of Steviol
Authors
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.
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.
Publication History
Received: 01 August 2025
Accepted after revision: 04 September 2025
Accepted Manuscript online:
04 September 2025
Article published online:
21 October 2025
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References
- 1 Yoder RA, Johnston JN. Chem Rev 2005; 105: 4730-4756
- 2 Fish PV, Johnson WS. Tetrahedron Lett 1994; 35: 1469-1472
- 3 Johnson WS, Telfer SJ, Cheng S, Schubert U. J Am Chem Soc 1987; 109: 2517-2518
- 4 Johnson WS, Lindell SD, Steele J. J Am Chem Soc 1987; 109: 5852-5853
- 5 Johnson WS. Bioorg Chem 1976; 5: 51-98
- 6 Johnson WS. Angew Chem Int Ed 1976; 15: 9-17
- 7 Xu M, Hillwig ML, Tiernan MS, Peters RJ. J Nat Prod 2017; 80: 328-333
- 8 Geisler K, Jensen NB, Yuen MM, Madilao L, Bohlmann J. Plant Physiol 2016; 171: 152-164
- 9 Helliwell CA, Chandler PM, Poole A, Dennis ES, Peacock WJ. Proc Natl Acad Sci U S A 2001; 98: 2065-2070
- 10 Ceunen S, Geuns JMC. J Nat Prod 2013; 76: 1201-1228
- 11 Cherney EC, Green JC, Baran PS. Angew Chem Int Ed 2013; 52: 9019-9022
- 12 Halperin SD, Britton R. Org Biomol Chem 2013; 11: 1702-1705
- 13 Goldsmith DJ, Phillips CF. J Am Chem Soc 1969; 91: 5862-5870
- 14 Michalak SE, Nam S, Kwon DM, Horne DA, Vanderwal CD. J Am Chem Soc 2019; 141: 9202-9206
- 15 Riehl PS, DePorre YC, Armaly AM, Groso EJ, Schindler CS. Tetrahedron 2015; 71: 6629-6650
- 16 Kolb HC, van Nieuwenhze MS, Sharpless KB. Chem Rev 1994; 94: 2483-2547
- 17 Noe MC, Letavic MA, Snow SL. Org React 2005; 66: 109-625
- 18 Mohammad S, Dhambri S, Gori D. et al. Synlett 2013; 24: 2581-2585
- 19 Marshall JA, Schaaf GM. J Org Chem 2003; 68: 7428-7432
- 20 Chen K, Shi Q, Fujioka T. et al. Bioorg Med Chem 1995; 3: 1345-1348
- 21 Bohlman F, Abraham W, Sherdlick WS. Phytochemistry 1980; 19: 869-871
- 22 El-Desoky AH, Kato H, Angkouw ED, Mangindaan RE, de Voogd NJ, Tsukamoto S. J Nat Prod 2016; 79: 1922-1928
- 23 Michalak SE. Synthesis of Cytotoxic Haterumaimide and Lissoclimide Natural Products. (Publication No. 22615359) [Doctoral dissertation, University of California Irvine] ProQuest Dissertations & Theses Global; 2019