Synthesis and binding studies of 2-arylapomorphines

Kåre Søndergaard; Jesper Langgaard Kristensen; Mikael Palner; Nic Gillings; Gitte Moos Knudsen; Bryan Roth; M. Begtrup

doi:10.1039/b507195j

Synthesis and binding studies of 2-arylapomorphines

Kåre Søndergaard, Jesper Langgaard Kristensen, Mikael Palner, Nic Gillings, Gitte Moos Knudsen, Bryan Roth, M. Begtrup

30 Citations (Scopus)

Abstract

From codeine, four different 2-aryl substituted apomorphines were synthesised in 6 steps each. Oxidation of codeine with IBX followed by acid catalysed rearrangement gave morphothebaine, which was selectively triflylated at the 2-position and subsequently O-acetylated at the 11-position. The resulting triflate was coupled in a Suzuki-Miyaura type reaction with a series of 4-substituted arylboronic esters which, after deprotection, gave the desired 2-aryl apomorphines. The analogues were tested for affinity towards a range of dopaminergic, serotonergic and adrenergic receptors. 2-(4-Hydroxyphenyl)- apomorphine exhibited high affinity for the dopamine D receptor. A putative ligand-receptor interaction was put forward.

Original language	English
Journal	Organic & Biomolecular Chemistry
Volume	3
Issue number	22
Pages (from-to)	4077-4081
Number of pages	5
ISSN	1477-0520
DOIs	https://doi.org/10.1039/b507195j
Publication status	Published - 21 Nov 2005

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AU - Søndergaard, Kåre

AU - Kristensen, Jesper Langgaard

AU - Palner, Mikael

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AU - Knudsen, Gitte Moos

AU - Roth, Bryan

AU - Begtrup, M.

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AB - From codeine, four different 2-aryl substituted apomorphines were synthesised in 6 steps each. Oxidation of codeine with IBX followed by acid catalysed rearrangement gave morphothebaine, which was selectively triflylated at the 2-position and subsequently O-acetylated at the 11-position. The resulting triflate was coupled in a Suzuki-Miyaura type reaction with a series of 4-substituted arylboronic esters which, after deprotection, gave the desired 2-aryl apomorphines. The analogues were tested for affinity towards a range of dopaminergic, serotonergic and adrenergic receptors. 2-(4-Hydroxyphenyl)- apomorphine exhibited high affinity for the dopamine D receptor. A putative ligand-receptor interaction was put forward.

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Synthesis and binding studies of 2-arylapomorphines

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