Abstract
The present thesis is focused on the design of synthetic routes towards asmarine analogues. Asmarines are marine natural products isolated from the sponges Raspalia sp. The asmarine molecule contains a seven-membered ring fused with a purine core. This tetrahydrodiazepinopurine moiety has previously been constructed for example by ringclosing metathesis (RCM). We were focused on developing this RCM reaction pathway further, in order to introduce a chiral centre to the 7-membered ring. The attempts to employ chiral allylic amines in the strategy were not successful. However, we managed to achieve the synthesis of the seven-membered ring by a novel synthetic approach employing Ru-catalysed double bond migration and Cu-catalysed C-N coupling. Thus, a new method for double bond migration of N-allyl purines was successfully developed, involving the substrate 7-allyl-6-iodo-7H-purine and the catalyst RuClH(CO)(PPh3)3. Furthermore, the possibilities of C-N bond formation between tert-butyl allylcarbamate and 7-alkylated 6-halopurines were investigated. Suitable conditions for the coupling were determined using the Goldberg reaction and 6-iodo-7-(prop-1-en-1-yl)-7Hpurine was successfully coupled with tert-butyl allylcarbamate, giving tert-butyl allyl(7-(prop-1-en-1-yl)-7H-purin-6-yl)carbamate. Finally, the RCM with this intermediate led to the previously known 7,8,9,10-tetrahydro-[1,4]diazepino[1,2,3-gh]purine. In addition, attention is paid to the synthesis and rearrangement of N-allyl to Npropenyl purines. There are very few convenient routes to N-alkenylpurines in general. Therefore, we have carried out a study on the isomerisation of 9-allyl- and 7-allylpurines. Various N-allyl purines were prepared, and base- or transition metal complex promoted isomerisations were explored. Subsequently, this study was extended for substrates bearing additional substitution on the allyl chain. Scope and limitation of the double bond migration methodologies and E/Z selectivity is discussed.
List of papers
| 1: Synthesis of N-Alkenylpurines by Rearrangements of the Corresponding N-Allyl Isomers: Scopes and Limitations. Jindrich Kania and Lise-Lotte Gundersen. European Journal of Organic Chemistry Volume 2013, Issue 10, pages 2008–2019, April 2013. The paper is removed from the thesis in DUO due to publisher restrictions. The published version is available at: https://doi.org/10.1002/ejoc.201201455 |