Stereoselective access to bioactive cyclopropanes (+)-PPCC and (1R,2S)-2-aminomethyl-1-arylcyclopropane-1-carboxamides from (−)-levoglucosenone

Ledingham, Edward T; Puschnig, Johannes; Greatrex, Ben W

doi:10.1016/j.tetlet.2025.155620

Author(s)

Ledingham, Edward T

Puschnig, Johannes

Greatrex, Ben W

Publication Date

2025-06-15

Abstract

The chiral synthon (− )-levoglucosenone (LGO) obtained from cellulose pyrolysis has been transformed into two known bioactive compounds: the serotonin-norepinephrine-dopamine reuptake inhibitor (1R,2S)-2-(aminomethyl)-N,N-diethyl-1-(naphthalen-2-yl)cyclopropane-1-carboxamide and the σ− receptor ligand (+)-PPCC. The key steps in the process were the arylation of an LGO derivative via a Suzuki-Miyaura cross-coupling reaction, then cyclopropanation under Johnson-Corey-Chaykovsky conditions. Dehomologation was achieved using Baeyer-Villiger and NaIO4 mediated oxidation, and then functional group interconversion gave the bioactive cyclopropanes. Several derivatives of each target were developed demonstrating the versatility of the process for aryl and amine group substitution.

Citation

Tetrahedron Letters, v.163, p. 1-5

ISSN

1873-3581

0040-4039

Link

https://hdl.handle.net/1959.11/70445

Language

en

Publisher

Elsevier Ltd

Title

Stereoselective access to bioactive cyclopropanes (+)-PPCC and (1R,2S)-2-aminomethyl-1-arylcyclopropane-1-carboxamides from (−)-levoglucosenone

Type of document

Journal Article

Entity Type

Publication

Author(s)	Ledingham, Edward T Puschnig, Johannes Greatrex, Ben W
Publication Date	2025-06-15
Abstract	<p>The chiral synthon (− )-levoglucosenone (LGO) obtained from cellulose pyrolysis has been transformed into two known bioactive compounds: the serotonin-norepinephrine-dopamine reuptake inhibitor (1<i>R</i>,2<i>S</i>)-2-(aminomethyl)-<i>N</i>,<i>N</i>-diethyl-1-(naphthalen-2-yl)cyclopropane-1-carboxamide and the σ− receptor ligand (+)-PPCC. The key steps in the process were the arylation of an LGO derivative via a Suzuki-Miyaura cross-coupling reaction, then cyclopropanation under Johnson-Corey-Chaykovsky conditions. Dehomologation was achieved using Baeyer-Villiger and NaIO<sub>4</sub> mediated oxidation, and then functional group interconversion gave the bioactive cyclopropanes. Several derivatives of each target were developed demonstrating the versatility of the process for aryl and amine group substitution.</p>
Citation	Tetrahedron Letters, v.163, p. 1-5
ISSN	1873-3581 0040-4039
Link	https://hdl.handle.net/1959.11/70445
Language	en
Publisher	Elsevier Ltd
Title	Stereoselective access to bioactive cyclopropanes (+)-PPCC and (1R,2S)-2-aminomethyl-1-arylcyclopropane-1-carboxamides from (−)-levoglucosenone
Type of document	Journal Article
Entity Type	Publication

Stereoselective access to bioactive cyclopropanes (+)-PPCC and (1R,2S)-2-aminomethyl-1-arylcyclopropane-1-carboxamides from (−)-levoglucosenone

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