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Evolution of a Strategy for the Enantioselective Total Synthesis of (+)-Psiguadial B

Chapman, Lauren M. and Beck, Jordan C. and Lacker, Caitlin R. and Wu, Linglin and Reisman, Sarah E. (2018) Evolution of a Strategy for the Enantioselective Total Synthesis of (+)-Psiguadial B. Journal of Organic Chemistry, 83 (11). pp. 6066-6085. ISSN 0022-3263. http://resolver.caltech.edu/CaltechAUTHORS:20180507-092121998

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Abstract

(+)-Psiguadial B is a diformyl phloroglucinol meroterpenoid that exhibits antiproliferative activity against the HepG2 human hepatoma cancer cell line. This full account details the evolution of a strategy that culminated in the first enantioselective total synthesis of (+)-psiguadial B. A key feature of the synthesis is the construction of the trans-cyclobutane motif by a Wolff rearrangement with in situ catalytic, asymmetric trapping of the ketene. An investigation of the substrate scope of this method to prepare enantioenriched 8-aminoquinolinamides is disclosed. Three routes toward (+)-psiguadial B were evaluated that featured the following key steps: (1) an ortho-quinone methide hetero-Diels–Alder cycloaddition to prepare the chroman framework, (2) a Prins cyclization to form the bridging bicyclo[4.3.1]decane system, and (3) a modified Norrish–Yang cyclization to generate the chroman. Ultimately, the successful strategy employed a ring-closing metathesis to form the seven-membered ring and an intramolecular O-arylation reaction to complete the polycyclic framework of the natural product.


Item Type:Article
Related URLs:
URLURL TypeDescription
https://doi.org/10.1021/acs.joc.8b00728DOIArticle
https://pubs.acs.org/doi/suppl/10.1021/acs.joc.8b00728PublisherSupporting Information
ORCID:
AuthorORCID
Reisman, Sarah E.0000-0001-8244-9300
Additional Information:© 2018 American Chemical Society. Received: March 22, 2018; Published: May 4, 2018. Prof. Greg Fu is gratefully acknowledged for insightful discussions. We thank Dr. Allen Oliver, Dr. Nathan Schley, and Ms. Julie Hofstra for X-ray crystallographic structure determination and Dr. David VanderVelde for assistance with NMR structure determination. We thank Dr. Scott Virgil and the Caltech Center for Catalysis and Chemical Synthesis for access to analytical equipment and Materia, Inc. for a donation of HG-II catalyst. Fellowship support was provided by the NSF (L.M.C. and C.R.L., Grant No. DGE-1144469), NIH Training Grant (J.C.B., Grant No. 5T32GM007616-39) and SNF (L.W., Grant No. PBZHP2-147311). S.E.R. is an American Cancer Society Research Scholar and a Heritage Medical Research Foundation Investigator. Financial support from the NSF (CAREER-1057143), the American Cancer Society, the Research Corporation Cottrell Scholars program, and DuPont is gratefully acknowledged. The authors declare no competing financial interest.
Group:Heritage Medical Research Institute
Funders:
Funding AgencyGrant Number
NSF Graduate Research FellowshipDGE-1144469
NIH Predoctoral Fellowship5T32GM007616-39
Swiss National Science Foundation (SNSF)PBZHP2-147311
American Cancer SocietyUNSPECIFIED
Heritage Medical Research InstituteUNSPECIFIED
NSFCHE-1057143
American Cancer SocietyUNSPECIFIED
Cottrell Scholar of Research CorporationUNSPECIFIED
DuPontUNSPECIFIED
Record Number:CaltechAUTHORS:20180507-092121998
Persistent URL:http://resolver.caltech.edu/CaltechAUTHORS:20180507-092121998
Official Citation:Evolution of a Strategy for the Enantioselective Total Synthesis of (+)-Psiguadial B. Lauren M. Chapman, Jordan C. Beck, Caitlin R. Lacker, Linglin Wu, and Sarah E. Reisman. The Journal of Organic Chemistry 2018 83 (11), 6066-6085 DOI: 10.1021/acs.joc.8b00728
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:86239
Collection:CaltechAUTHORS
Deposited By: Tony Diaz
Deposited On:07 May 2018 17:11
Last Modified:04 Jun 2018 21:46

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