Mainz
Asymmetrische Synthese von Sordidin, 7-epi-Sordidin und von Polyoeinheiten mit quartären Stereozentren
Abstract
dc:descriptionPheromones have become very important in phytosanitary strategies. Within the thesis the first asymmetric synthesis of (+)-sordidin and (-)-7-epi-sordidin, aggregation pheromones of the banana weevil Cosmopolites sordidus which is the most important world-wide insect pest of banana plants has been achieved. Starting from dioxanone RAMP-hydrazone the desired C-7 epimers were prepared in 39% overall yield as a 1.5: 1 diastereomeric mixture over 14 steps. The epimers could be separated by preparative GC and thus, each of them could be obtained in high diastereomeric and enantiomeric purity (de > 97%, ee > 98%). Their NMR spectroscopic data and optical rotation values are consistent with those given in the literature. Furthermore, a synthesis strategy towards alpha,alpha´-quaternary, alpha,alpha´-dimethylated 2-keto-1,3-diols could be developed. This characteristic structural feature could be found in several biologically active natural products such as anisatin which proved to be a potent neurotoxin. In addition, staminol A which was isolated from the Vietnamese medical plant called Orthosiphon stamineus BENTH. and is used in treating jaundice, rheumatism, hepatitis, influenca and colon carcinoma as well as citreoviral, a specific inhibitor for mitochondrial therapy belong to this class of substrat. Within this thesis these diverse substituted alpha, alpha´-quatenary 2-keto-1,3-diols could be generated starting from easily available dioxanone SAMP-hydrazone in 14-61% yield over five steps. The protocol included 4 consecutive and diastereoselective alpha-alkylation steps, thereof two alpha-quaternarisation steps, the last one carried out in the presence of DMPU, employing the SAMP/RAMP-hydrazone methodology developed by Enders et al. After subsequent acidic cleavage of both the chiral auxiliary and the acetal moiety these 2-keto-1,3-diols bearing two quaternary stereocenters could be obtained with high stereoselectivity (de > 79-97%, ee > 96-99%). Additionally, a diastereo- and enantioselective access to 1,2-quaternary, 1,3-protected 1,2,3-triols was achieved via substituent-controlled nucleophilic 1,2-addition to the carbonyl group of the dioxanone system. Another essential part of the thesis was focused on the synthesis of a mono-protected sugar unit called 4´-epi-2-C-methyl-D-5-deoxyribose whose unprotected C-4 epimer could be found as an unusual sugar in trachycladine A and B. Both were isolated from a marine sponge Trachycladus laevispirulifer which thrives in the gulf of Exmouth in Western Australia and belong to the class of nucleosides. In recent tests trachycladine A showed in vitro cytotoxicity against sevaral cell lines including leukaemia, colon and breast tumors. Again starting from dioxanone SAMP-hydrazone the synthesis of the MOM-protected 4´-epi-2-C-methyl-D-5-deoxyribose could be completed in nine steps providing an anomeric mixture (dr = 3:1) in 35% overall yield. Further, the TBS-protected precursor of 4´-epi-2-C-methyl-D-5-deoxyribose was synthesized over 8 steps in 47% yield. A subsequent coupling of the lactols towards the corresponding purine bases, hypoxanthine and chloroadenine applying the Vorbrüggen protocol should – after deprotection of the hydroxyl function – result in 4´-epi trachycladine A and B.
Degree
thesis:*- Grantor dc:publisher
- Mainz
- Year dc:date
- 2005
Author and committee
dc:creator, dc:contributor.*- Author dc:creator
-
- Breuer, Irene
- Contributors dc:contributor
-
- Enders, Dieter
Subjects
dc:subject × 11Rights
dc:rights- Statement dc:rights
-
- info:eu-repo/semantics/openAccess
- Language dc:language
- ger