Universität zu Köln

Griesbeck, Axel G. ORCID: 0000-0002-6546-3482, Braeutigam, Maria, Kleczka, Margarethe and Raabe, Angela (2017). Synthetic Approaches to Mono- and Bicyclic Perortho-Esters with a Central 1,2,4-Trioxane Ring as the Privileged Lead Structure in Antimalarial and Antitumor-Active Peroxides and Clarification of the Peroxide Relevance. Molecules, 22 (1). BASEL: MDPI. ISSN 1420-3049

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Abstract

The synthesis of 4-styryl-substituted 2,3,8-trioxabicyclo[3.3.1]nonanes, peroxides with the core structure of the bioactive 1,2,4-trioxane ring, was conducted by a multistep route starting from the aryl methyl ketones 1a-1c. Condensation and reduction/oxidation delivered enals 4a-4c that were coupled with ethyl acetate and reduced to the 1,3-diol substrates 6a-6c. Highly diastereoselective photooxygenation delivered the hydroperoxides 7a-7c and subsequent PPTS (pyridinium-p-toluenesulfonic acid)-catalyzed peroxyacetalization with alkyl triorthoacetates gave the cyclic peroxides 8a-8e. These compounds in general show only moderate antimalarial activities. In order to extend the repertoire of cyclic peroxide structure, we aimed for the synthesis of spiro-perorthocarbonates from orthoester condensation of -hydroxy hydroperoxide 9 but could only realize the monocyclic perorthocarbonate 10. That the central peroxide moiety is the key structural motif in anticancer active GST (glutathione S-transferase)-inhibitors was elucidated by the synthesis of a 1,3-dioxane 15with a similar substitution pattern as the pharmacologically active peroxide 11via a singlet oxygen ene route from the homoallylic alcohol 12.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Griesbeck, Axel G. UNSPECIFIED orcid.org/0000-0002-6546-3482 UNSPECIFIED Braeutigam, Maria UNSPECIFIED UNSPECIFIED UNSPECIFIED Kleczka, Margarethe UNSPECIFIED UNSPECIFIED UNSPECIFIED Raabe, Angela UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-247283
DOI:	10.3390/molecules22010119
Journal or Publication Title:	Molecules
Volume:	22
Number:	1
Date:	2017
Publisher:	MDPI
Place of Publication:	BASEL
ISSN:	1420-3049
Language:	English
Faculty:	Faculty of Mathematics and Natural Sciences
Divisions:	Faculty of Mathematics and Natural Sciences > Department of Chemistry > Institute of Organic Chemistry
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language ARTEMISININ DERIVATIVES; QINGHAOSU ARTEMISININ; ALLYLIC ALCOHOLS; PHOTOOXYGENATION; ANTICANCER; MALARIA; DRUG; DIMERS; CONSTRUCTION; EFFICACY Multiple languages Biochemistry & Molecular Biology; Chemistry, Multidisciplinary Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/24728