Rapid Syntheses of (-)-FR901483 and (+)-TAN1251C Enabled by Complexity-Generating Photocatalytic Olefin Hydroaminoalkylation.
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Peer-reviewed
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Abstract
We report a common strategy to facilitate the syntheses of the polycyclic alkaloids (-)-FR901483 (1) and (+)-TAN1251C (2). A divergent synthetic strategy provides access to both natural products through a pivotal spirolactam intermediate (3), which can be accessed on a gram-scale. A photocatalytic olefin hydroaminoalkylation brings together three readily available building blocks and forges the majority of the carbon framework present in 1 and 2 in a single operation, leading to concise total syntheses. The complexity-generating photocatalytic process also provides direct access to novel non-racemic spirolactam scaffolds that are likely to be of interest to early-stage drug discovery programs.
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Keywords
amine synthesis, medicinal chemistry, photoredox chemistry, radical chemistry, total synthesis
Journal Title
Angew Chem Int Ed Engl
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Journal ISSN
1433-7851
1521-3773
1521-3773
Volume Title
59
Publisher
Wiley
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All rights reserved
Sponsorship
Engineering and Physical Sciences Research Council (EP/S020292/1)
The Royal Society (wm140104)
The Royal Society (wm140104)
AstraZeneca, Herchel Smith Scholarship Scheme, EPSRC (EP/S020292/1), Royal Society