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The Enantioselective Synthesis of Eburnamonine, Eucophylline, and 16′-epi-Leucophyllidine

Reimann, Christopher E. and Ngamnithiporn, Aurapat and Hayashida, Kohei and Saito, Daisuke and Korch, Katerina M. and Stoltz, Brian M. (2021) The Enantioselective Synthesis of Eburnamonine, Eucophylline, and 16′-epi-Leucophyllidine. Angewandte Chemie International Edition, 60 (33). pp. 17957-17962. ISSN 1433-7851. PMCID PMC8338904. doi:10.1002/anie.202106184. https://resolver.caltech.edu/CaltechAUTHORS:20210527-093457752

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Abstract

A synthetic approach to the heterodimeric bisindole alkaloid leucophyllidine is disclosed herein. An enantioenriched lactam building block, synthesized through palladium-catalyzed asymmetric allylic alkylation, served as the precursor to both hemispheres. The eburnamonine-derived fragment was synthesized through a Bischler–Napieralski/hydrogenation approach, while the eucophylline-derived fragment was synthesized by Friedländer quinoline synthesis and two sequential C−H functionalization steps. A convergent Stille coupling and phenol-directed hydrogenation united the two monomeric fragments to afford 16′-epi-leucophyllidine in 21 steps from commercial material.


Item Type:Article
Related URLs:
URLURL TypeDescription
https://doi.org/10.1002/anie.202106184DOIArticle
ORCID:
AuthorORCID
Reimann, Christopher E.0000-0003-3274-7590
Ngamnithiporn, Aurapat0000-0002-5389-8171
Korch, Katerina M.0000-0002-1436-8792
Stoltz, Brian M.0000-0001-9837-1528
Additional Information:© 2021 Wiley-VCH. Issue Online: 03 August 2021; Version of Record online: 06 July 2021; Accepted manuscript online: 25 May 2021; Manuscript received: 07 May 2021. We thank the NIH-NIGMS (R01GM080269) for financial support. Portions of this research were also funded by the NSF under the CCI Center for Selective C−H functionalization (CCHF) CHE-1700982. A.N. thanks the Royal Thai Government Scholarship Program. D.S. and K.H. thank Nippon Chemiphar for funding. We thank Dr. David VanderVelde (Caltech) for NMR expertise, Dr. Scott Virgil (Caltech) for instrumentation and analytical support, Dr. Michael Takase and Larry Henling (Caltech) for assistance with X-ray analysis, and Dr. Mona Shahgholi and Naseem Torian (Caltech) for mass spectroscopy. Professor Toh-Seok Kam (U. of Malaya) is acknowledged for providing a sample of leucophyllidine for direct analytical comparison. The authors declare no conflict of interest.
Funders:
Funding AgencyGrant Number
NIHR01GM080269
NSFCHE-1700982
Royal Thai Government Scholarship ProgramUNSPECIFIED
Nippon ChemipharUNSPECIFIED
Subject Keywords:alkaloids; convergence; cross-coupling; divergence; total synthesis
Issue or Number:33
PubMed Central ID:PMC8338904
DOI:10.1002/anie.202106184
Record Number:CaltechAUTHORS:20210527-093457752
Persistent URL:https://resolver.caltech.edu/CaltechAUTHORS:20210527-093457752
Official Citation:The Enantioselective Synthesis of Eburnamonine, Eucophylline, and 16′-epi-Leucophyllidine. C. E. Reimann, A. Ngamnithiporn, K. Hayashida, D. Saito, K. M. Korch, B. M. Stoltz, Angew. Chem. Int. Ed. 2021, 60, 17957; DOI: 10.1002/anie.202106184
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:109281
Collection:CaltechAUTHORS
Deposited By: George Porter
Deposited On:27 May 2021 17:10
Last Modified:11 Aug 2021 16:52

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