Craig, Robert A., II and Smith, Russell C. and Roizen, Jennifer L. and Jones, Amanda C. and Virgil, Scott C. and Stoltz, Brian M. (2018) Development of a Unified Enantioselective, Convergent Synthetic Approach Toward the Furanobutenolide-Derived Polycyclic Norcembranoid Diterpenes: Asymmetric Formation of the Polycyclic Norditerpenoid Carbocyclic Core by Tandem Annulation Cascade. Journal of Organic Chemistry, 83 (7). pp. 3467-3485. ISSN 0022-3263. PMCID PMC5889334. doi:10.1021/acs.joc.7b02825. https://resolver.caltech.edu/CaltechAUTHORS:20180327-133635374
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Abstract
An enantioselective and diastereoselective approach toward the synthesis of the tetracyclic scaffold of the furanobutenolide-derived polycyclic norditerpenoids is described. Focusing on synthetic efforts toward ineleganolide, the synthetic approach utilizes a palladium-catalyzed enantioselective allylic alkylation for the construction of the requisite chiral tertiary ether. A diastereoselective cyclopropanation–Cope rearrangement cascade enabled the convergent assembly of the ineleganolide [6,7,5,5]-tetracyclic scaffold. Investigation of substrates for this critical tandem annulation process is discussed along with synthetic manipulations of the [6,7,5,5]-tetracyclic scaffold and the attempted interconversion of the [6,7,5,5]-tetracyclic scaffold of ineleganolide to the isomeric [7,6,5,5]-core of scabrolide A and its naturally occurring isomers. Computational evaluation of ground-state energies of late-stage synthetic intermediates was used to guide synthetic development and aid in the investigation of the conformational rigidity of these highly constrained and compact polycyclic structures.
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Alternate Title: | The Development of a Unified Enantioselective, Convergent Synthetic Approach Toward the Furanobutenolide-Derived Polycyclic Norcembranoid Diterpenes: Asymmetric Formation of the Polycyclic Norditerpenoid Carbocyclic Core by Tandem Annulation Cascade | ||||||||||||||||||
Additional Information: | © 2018 American Chemical Society. Received: December 4, 2017; Published: February 21, 2018. We thank the NIH-NIGMS (R01GM080269), Amgen, the Gordon and Betty Moore Foundation, and Caltech for financial support and Eli Lilly & Co. for assistance with biological activity screening. Additionally, we gratefully acknowledge Larry Henling and Dr. Michael Takase (Caltech) for X-ray crystallographic structural determination, Dr. Mona Shahgholi and Naseem Torian (Caltech) for mass spectrometry assistance, and Dr. David VanderVelde (Caltech) for NMR experimental assistance and helpful discussions. Additionally, Prof. Sarah Reisman, Dr. Jeffrey C. Holder, Dr. Corey M. Reeves, Prof. Hosea M. Nelson, Dr. Jonny R. Gordon, Dr. Pamela M. Tadross, and Beau P. Pritchett (Caltech) are thanked for helpful discussions. R.A.C. gratefully acknowledges the support of this work provided by a fellowship from the National Cancer Institute of the National Institutes of Health (NIH) under Award No. F31A17435. J.L.R. thanks the California Tobacco-Related Disease Research Program of the University of California, Grant No. 14DT-0004 for a predoctoral fellowship. A.C.J. thanks the NIH for the support of this work provided by a postdoctoral fellowship (Award No. F32GM082000). | ||||||||||||||||||
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Issue or Number: | 7 | ||||||||||||||||||
PubMed Central ID: | PMC5889334 | ||||||||||||||||||
DOI: | 10.1021/acs.joc.7b02825 | ||||||||||||||||||
Record Number: | CaltechAUTHORS:20180327-133635374 | ||||||||||||||||||
Persistent URL: | https://resolver.caltech.edu/CaltechAUTHORS:20180327-133635374 | ||||||||||||||||||
Official Citation: | Development of a Unified Enantioselective, Convergent Synthetic Approach Toward the Furanobutenolide-Derived Polycyclic Norcembranoid Diterpenes: Asymmetric Formation of the Polycyclic Norditerpenoid Carbocyclic Core by Tandem Annulation Cascade. Robert A. Craig, II, Russell C. Smith, Jennifer L. Roizen, Amanda C. Jones, Scott C. Virgil, and Brian M. Stoltz. The Journal of Organic Chemistry 2018 83 (7), 3467-3485. DOI: 10.1021/acs.joc.7b02825 | ||||||||||||||||||
Usage Policy: | No commercial reproduction, distribution, display or performance rights in this work are provided. | ||||||||||||||||||
ID Code: | 85462 | ||||||||||||||||||
Collection: | CaltechAUTHORS | ||||||||||||||||||
Deposited By: | Tony Diaz | ||||||||||||||||||
Deposited On: | 27 Mar 2018 21:01 | ||||||||||||||||||
Last Modified: | 15 Mar 2022 19:52 |
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