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Enzymatic Kinetic Resolution of 1-(3-furyl)-3-buten-1ol
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry, Organic Pharmaceutical Chemistry.
Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Biochemistry and Organic Chemistry, Organic Chemistry. Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry, Organic Chemistry.ORCID iD: 0000-0002-9092-261X
2005 (English)In: Tetrahedron: asymmetry, ISSN 0957-4166, E-ISSN 1362-511X, Vol. 16, 2397-2399 p.Article in journal (Other academic) Published
Abstract [en]

The enzymatic kinetic resolution of 1-(3-furyl)-3-buten-1-ol was investigated via the enantioselective hydrolysis of the corresponding acetate. Pseudomonas fluorescens (Fluka) was found to give the highest enantiomeric ratios of the 11 lipases screened. At 51% conversion, the ee value (eep) for the product was found to be 89%, giving an enantiomeric ratio (Ep) of 58, while the ee value (ees) for the substrate was 89%, giving an enantiomeric ratio (Ep) of 38.

Place, publisher, year, edition, pages
Elsevier, 2005. Vol. 16, 2397-2399 p.
National Category
Organic Chemistry
Research subject
Chemistry with specialization in Organic Chemistry
Identifiers
URN: urn:nbn:se:uu:diva-92719DOI: 10.1016/j.tetasy.2005.06.013OAI: oai:DiVA.org:uu-92719DiVA: diva2:165898
Available from: 2005-03-10 Created: 2005-03-10 Last updated: 2017-12-14
In thesis
1. Synthesis of Molecular Probes for Exploring the Human Consciousness, 5-HT7 Ligands and Salvinorins
Open this publication in new window or tab >>Synthesis of Molecular Probes for Exploring the Human Consciousness, 5-HT7 Ligands and Salvinorins
2005 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

In this study, we have addressed the serotonergic and the opioid system within the CNS. Both systems are of outmost importance in the etiology of disease states, especially mental disorders.

In our investigation of the serotonergic system, we have synthesized novel enantiomerically pure 6-aryl-3-amino- and 8-aryl-3-aminochromans as ligands for the 5-HT7 receptor. One reason for the lack of understanding of the physiological functionality of the serotonin 5-HT7 receptor, the most recently discovered member of the serotonin receptor family, is the absence of partial agonists and agonists. In this series, we have identified partial agonists with more than189 fold selectivity over the 5-HT1A receptor and one agonist with 29 fold greater selectivity over the serotonin 5-HT1A receptor. Thus the present series constitutes a starting point for developing highly selective ligands for the 5-HT7 receptor.

In our investigation of the opioid system, our focus has been on the natural product salvinorin A, which is a highly selective kappa opioid receptor agonist. In the total synthesis of salvinorin A, we have accomplished the synthesis of a key intermediate, 6-(3-furyl)-4-methyl-5,6-dihydro-pyran-2-one via ring closing metathesis. Furthermore, synthetic methodologies have been developed as a part of the total synthesis. Several lipases have been screeened for their ability to generate enantiomerically pure 1-(3-Furyl)-3-buten-1-ol via bio-catalyzed hydrolysis of the corresponding acetate. The lipase from Pseudomonas fluorescens was identified as having stereoselectivity high enough to generate a % ee value above 98%. We have also developed a route for the introduction of a hydroxyl functionality in the γ position of α,β-unsaturated cyclic ketones by the regioselective oxidation of 1-silyloxy-1,3-dienes using dimethyldioxirane. We have initiated the investigation of the pharmacophore responsible for the kappa opioid activity by synthesizing simplified analogues of salvinorin A. A synthetic route providing easy access to simplified analogues of salvinorin A have been established.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2005. 107 p.
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Pharmacy, ISSN 1651-6192 ; 4
Keyword
Pharmaceutical chemistry, serotonin system, opioid system, selective 5-HT7 agonist, 3-aminchromans, salvinorin A, selective kappa opioid receptor, mental disorders, consciousness, regioselective oxidation, enzymatic kinetic resolution, Farmaceutisk kemi
National Category
Medicinal Chemistry
Identifiers
urn:nbn:se:uu:diva-4824 (URN)91-554-6173-5 (ISBN)
Public defence
2005-03-31, Room B22, Uppsala Biomedicinska Centrum, Husargatan 3, Uppsala, 10:15
Opponent
Supervisors
Available from: 2005-03-10 Created: 2005-03-10Bibliographically approved

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Gogoll, Adolf

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