ASCA GmbH Angewandte Synthesechemie Adlershof

Berlin, Germany

ASCA GmbH Angewandte Synthesechemie Adlershof

Berlin, Germany
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Braun B.,ASCA Angewandte Synthesechemie Adlershof GmbH | Koppen R.,BAM Federal Institute of Materials Research and Testing | Wedler C.,ASCA Angewandte Synthesechemie Adlershof GmbH | Theil F.,ASCA Angewandte Synthesechemie Adlershof GmbH
Natural Product Communications | Year: 2017

The priority ergot alkaloids ergometrine and ergometrinine are highly toxic mycotoxins naturally occurring in different types of grains (i.e. rye, wheat, rice), as well as grain-based foods and, therefore, have gained increasing importance for food safety over the last years. The application of HPLC-MS/MS for the analysis of ergot alkaloids in food presupposes the availability of isotopically labelled internal standards. Thus, a multistep synthesis was developed for ergometrine-(N-13CD3) and its epimer ergometrinine-(N-13CD3) with a mass shift of four units compared with the parent compounds. The synthesis is based on the preparation of stable isotope labelled lysergic acid that was coupled with (S)-alaninol. The chemical synthesis of both compounds has been achieved in six steps with an overall yield of 1 % (ergometrine-(N-13CD3)) and 0.6 % (ergometrinine-(N-13CD3)), respectively. Structural identification was performed by MS analysis as well as 1H and13C NMR.


Gebauer J.,ASCA GmbH Angewandte Synthesechemie Adlershof | Werneburg M.,BAM Federal Institute of Materials Research and Testing | Koch M.,BAM Federal Institute of Materials Research and Testing
Natural Product Communications | Year: 2014

Trichodiene is the first and only volatile intermediate in the biosynthesis of Fusarium mycotoxins and its detection in the gas-phase might therefore be of potential interest as a marker for food safety analysis. We herein present an improved diastereoselective synthesis of trichodiene which can be used as an analytical standard for a headspace gas chromatography / mass spectrometry method to be developed.


Schunk S.,Grunenthal GmbH | Linz K.,Grunenthal GmbH | Hinze C.,Grunenthal GmbH | Frormann S.,Grunenthal GmbH | And 13 more authors.
ACS Medicinal Chemistry Letters | Year: 2014

In a previous communication, our efforts leading from 1 to the identification of spiro[cyclohexane-dihydropyrano[3,4-b]indole]-amine 2a as analgesic NOP and opioid receptor agonist were disclosed and their favorable in vitro and in vivo pharmacological properties revealed. We herein report our efforts to further optimize lead 2a, toward trans-6′-fluoro-4′, 9′-dihydro-N,N-dimethyl-4-phenyl-spiro[cyclohexane-1,1′(3′H) -pyrano[3,4-b]indol]-4-amine (cebranopadol, 3a), which is currently in clinical development for the treatment of severe chronic nociceptive and neuropathic pain. © 2014 American Chemical Society.


Schunk S.,Grunenthal GmbH | Linz K.,Grunenthal GmbH | Frormann S.,Grunenthal GmbH | Hinze C.,Grunenthal GmbH | And 13 more authors.
ACS Medicinal Chemistry Letters | Year: 2014

We report the discovery of spiro[cyclohexane-pyrano[3,4-b]indole]-amines, as functional nociceptin/orphanin FQ peptide (NOP) and opioid receptor agonists with strong efficacy in preclinical models of acute and neuropathic pain. Utilizing 4-(dimethylamino)-4-phenylcyclo-hexanone 1 and tryptophol in an oxa-Pictet-Spengler reaction led to the formation of spiroether 2, representing a novel NOP and opioid peptide receptor agonistic chemotype. This finding initially stems from the systematic derivatization of 1, which resulted in alcohols 3-5, ethers 6 and 7, amines 8-10, 22-24, and 26-28, amides 11 and 25, and urea 12, many with low nanomolar binding affinities at the NOP and mu opioid peptide (MOP) receptors. © 2014 American Chemical Society.


PubMed | ASCA GmbH Angewandte Synthesechemie Adlershof and Preclinical Drug Safety
Type: Journal Article | Journal: ACS medicinal chemistry letters | Year: 2014

We report the discovery of spiro[cyclohexane-pyrano[3,4-b]indole]-amines, as functional nociceptin/orphanin FQ peptide (NOP) and opioid receptor agonists with strong efficacy in preclinical models of acute and neuropathic pain. Utilizing 4-(dimethylamino)-4-phenylcyclo-hexanone 1 and tryptophol in an oxa-Pictet-Spengler reaction led to the formation of spiroether 2, representing a novel NOP and opioid peptide receptor agonistic chemotype. This finding initially stems from the systematic derivatization of 1, which resulted in alcohols 3-5, ethers 6 and 7, amines 8-10, 22-24, and 26-28, amides 11 and 25, and urea 12, many with low nanomolar binding affinities at the NOP and mu opioid peptide (MOP) receptors.


PubMed | ASCA GmbH Angewandte Synthesechemie Adlershof and Preclinical Drug Safety
Type: Journal Article | Journal: ACS medicinal chemistry letters | Year: 2014

In a previous communication, our efforts leading from 1 to the identification of spiro[cyclohexane-dihydropyrano[3,4-b]indole]-amine 2a as analgesic NOP and opioid receptor agonist were disclosed and their favorable in vitro and in vivo pharmacological properties revealed. We herein report our efforts to further optimize lead 2a, toward trans-6-fluoro-4,9-dihydro-N,N-dimethyl-4-phenyl-spiro[cyclohexane-1,1(3H)-pyrano[3,4-b]indol]-4-amine (cebranopadol, 3a), which is currently in clinical development for the treatment of severe chronic nociceptive and neuropathic pain.

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