Synthesis and binding studies of 2-arylapomorphines

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

Research output: Contribution to journal › Journal article › Research › peer-review

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 D2 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
ISSN	1477-0520
DOIs	https://doi.org/10.1039/b507195j
Publication status	Published - 21. Nov 2005
Externally published	Yes

Keywords

Animals
Apomorphine/chemical synthesis
Humans
Ligands
Male
Molecular Structure
Rats
Rats, Sprague-Dawley
Receptors, Biogenic Amine/metabolism
Receptors, Dopamine D2/metabolism

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title = "Synthesis and binding studies of 2-arylapomorphines",

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 D2 receptor. A putative ligand-receptor interaction was put forward.",

keywords = "Animals, Apomorphine/chemical synthesis, Humans, Ligands, Male, Molecular Structure, Rats, Rats, Sprague-Dawley, Receptors, Biogenic Amine/metabolism, Receptors, Dopamine D2/metabolism",

author = "K{\aa}re S{\o}ndergaard and Kristensen, {Jesper Langgaard} and Mikael Palner and Nic Gillings and Knudsen, {Gitte Moos} and Roth, {Bryan L} and Mikael Begtrup",

year = "2005",

month = nov,

day = "21",

doi = "10.1039/b507195j",

language = "English",

volume = "3",

pages = "4077--4081",

journal = "Organic & Biomolecular Chemistry",

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publisher = "Royal Society of Chemistry",

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TY - JOUR

T1 - Synthesis and binding studies of 2-arylapomorphines

AU - Søndergaard, Kåre

AU - Kristensen, Jesper Langgaard

AU - Palner, Mikael

AU - Gillings, Nic

AU - Knudsen, Gitte Moos

AU - Roth, Bryan L

AU - Begtrup, Mikael

PY - 2005/11/21

Y1 - 2005/11/21

N2 - 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 D2 receptor. A putative ligand-receptor interaction was put forward.

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 D2 receptor. A putative ligand-receptor interaction was put forward.

KW - Animals

KW - Apomorphine/chemical synthesis

KW - Humans

KW - Ligands

KW - Male

KW - Molecular Structure

KW - Rats

KW - Rats, Sprague-Dawley

KW - Receptors, Biogenic Amine/metabolism

KW - Receptors, Dopamine D2/metabolism

U2 - 10.1039/b507195j

DO - 10.1039/b507195j

M3 - Journal article

C2 - 16267586

SN - 1477-0520

VL - 3

SP - 4077

EP - 4081

JO - Organic & Biomolecular Chemistry

JF - Organic & Biomolecular Chemistry

IS - 22

ER -

Synthesis and binding studies of 2-arylapomorphines

Abstract

Keywords

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