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The total synthesis of (-)-cyanthiwigin F by means of double catalytic enantioselective alkylation

Enquist, John A., Jr. and Stoltz, Brian M. (2008) The total synthesis of (-)-cyanthiwigin F by means of double catalytic enantioselective alkylation. Nature, 453 (7199). pp. 1228-1231. ISSN 0028-0836. PMCID PMC2474750. http://resolver.caltech.edu/CaltechAUTHORS:20170216-150759253

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Abstract

Double catalytic enantioselective transformations are powerful synthetic methods that can facilitate the construction of stereochemically complex molecules in a single operation. In addition to generating two or more stereocentres in a single reaction, multiple asymmetric reactions also impart increased enantiomeric excess to the final product in comparison with the analogous single transformation. Furthermore, multiple asymmetric operations have the potential to independently construct several stereocentres at remote points within the same molecular scaffold, rather than relying on pre-existing chiral centres that are proximal to the reactive site. Despite the inherent benefits of multiple catalytic enantioselective reactions, their application to natural product total synthesis remains largely underutilized. Here we report the use of a double stereoablative enantioselective alkylation reaction in a concise synthesis of the marine diterpenoid (-)-cyanthiwigin F (ref. 8). By employing a technique for independent, selective formation of two stereocentres in a single stereoconvergent operation, we demonstrate that a complicated mixture of racemic and meso diastereomers may be smoothly converted to a synthetically useful intermediate with exceptional enantiomeric excess. The stereochemical information generated by means of this catalytic transformation facilitates the easy and rapid completion of the total synthesis of this marine natural product.


Item Type:Article
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https://dx.doi.org/10.1038/nature07046DOIArticle
http://www.nature.com/nature/journal/v453/n7199/full/nature07046.htmlPublisherArticle
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2474750/PubMed CentralArticle
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ORCID:
AuthorORCID
Stoltz, Brian M.0000-0001-9837-1528
Additional Information:© 2008 Macmillan Publishers Limited. Received 26 November 2007; accepted 2 May 2008. The authors wish to thank NIH-NIGMS (R01GM080269-01), Amgen, Abbott, Boehringer Ingelheim, Merck and Bristol-Myers Squibb for financial support. We also wish to thank M. W. Day and L. M. Henling for X-ray crystallographic expertise, S. Virgil, A. Harned, D. White, D. Caspi and J. T. Mohr for helpful discussions, and M. T. Hamann for an authentic sample and spectra of cyanthiwigin F. We thank E. J. Corey for guidance and mentorship, on the occasion of his 80th birthday. Crystallographic data have been deposited at the Cambridge Crystallographic Data Centre, 12 Union Road, Cambridge CB2 1EZ, UK, and copies can be obtained on request, free of charge, by quoting the publication citation and the deposition number 664430.
Funders:
Funding AgencyGrant Number
NIHR01GM080269-01
AmgenUNSPECIFIED
Abbott LaboratoriesUNSPECIFIED
Boehringer-IngelheimUNSPECIFIED
MerckUNSPECIFIED
Bristol-Myers SquibbUNSPECIFIED
PubMed Central ID:PMC2474750
Record Number:CaltechAUTHORS:20170216-150759253
Persistent URL:http://resolver.caltech.edu/CaltechAUTHORS:20170216-150759253
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:74393
Collection:CaltechAUTHORS
Deposited By: George Porter
Deposited On:17 Feb 2017 15:43
Last Modified:17 Feb 2017 15:43

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