CC BY-ND-NC 4.0 · Synthesis 2019; 51(01): 213-224
DOI: 10.1055/s-0037-1610395
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Asymmetric Total Synthesis and Biological Evaluation of (+)-Cycloclavine

Stephanie R. McCabe
,
Department of Chemistry, University of Pittsburgh, Pittsburgh, PA 15260, USA   Email: pwipf@pitt.edu
› Author Affiliations
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.
Further Information

Publication History

Received: 29 October 2018

Accepted: 31 October 2018

Publication Date:
20 November 2018 (eFirst)

  

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.

Supporting Information

 
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