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CC BY-ND-NC 4.0 · Synthesis 2019; 51(01): 213-224
DOI: 10.1055/s-0037-1610395
DOI: 10.1055/s-0037-1610395
feature
Asymmetric Total Synthesis and Biological Evaluation of (+)-Cycloclavine
The authors are grateful to Boehringer-Ingelheim Pharmaceuticals Inc., Ridgefield CT, for partial financial support of this work. SRM also acknowledges support from the Mary E. Warga and the University of Pittsburgh Arts and Sciences Mellon Fellowships.Weitere Informationen
Publikationsverlauf
Received: 29. Oktober 2018
Accepted: 31. Oktober 2018
Publikationsdatum:
20. November 2018 (online)
Published as part of the 50 Years SYNTHESIS – Golden Anniversary Issue
Abstract
The first total synthesis of natural (+)-cycloclavine uses a catalytic asymmetric cyclopropanation of allene, a regiospecific Pd-catalyzed enone formation, and two intramolecular Diels–Alder reactions for indole/indoline annulations. The binding properties of natural (+)- and unnatural (–)-cycloclavine on 16 CNS receptors revealed significant stereospecificity and unique binding profiles in comparison to LSD, psilocin, and DMT. Differential 5-HT affinities, as well as novel sigma-1 receptor properties bode well for potential therapeutic developments of clavine alkaloid scaffolds.
Key words
clavine ergot alkaloids - enantioselective allene cyclopropanation - psychedelics - stereospecific GPCR binding - LSD - psilocin - DMT - 5-HTA - sigma-1 receptorsSupporting Information
- Supporting information for this article is available online at https://doi.org/10.1055/s-0037-1610395. Spectral data (1H and 13C NMR for selected new compounds and (+)-cycloclavine).
- Supporting Information
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