Publikationsserver der RWTH Aachen University
Asymmetrische Synthese von Stigmolon und Untersuchungen zur asymmetrischen Synthese von (-)-Cytoxazon und Galbonolid A und B
Abstract
dc:descriptionIn this dissertation the asymmetric synthesis of both enantiomers of the fruiting body inducing phero-mone Stigmolone was achieved successfully using the SAMP/RAMP-method. Previously there was no synthesis known which involved a regioselective alpha-alkylation of unsymmetric dialkylhydrazones (R ≠ Me). After cleavage of the auxiliary, both Stigmolone enantiomers were synthesised with very good ee-values using a Cobalt-catalysed oxidative-reductive hydratation. For the first time the Co-catalysed reaction was applied to ketofunctionalised, enantiomerically pure and racemisation sensi-tive molecules using compressed air, which is a dramatic improvement of this reaction. The yield over five steps of (R)-Stigmolone (ee = 89%) was 6% (18% based on recovered starting material) and the yield of (S)-Stigmolone (ee = 93%) was 18% (20% based on recovered starting material). Without further modifications of the synthetic pathway the retrosynthesis of the cytokine modulator (–)-Cytoxazone also allows access to other cis-4,5-disubstituted oxazolidin-2-ones. After the development of a general protecting group strategy, the literature known starting material synthesis was revised in terms of yield and costs. Through alpha-alkylation and 1,2-addition of p-anisyl lithium to SAMP-hydrazones, the hydrazines were achieved as diastereo- and enantiomerically pure compounds with good yields. Syntheses of 3-SMP substituted cis-oxazolidin-2-ones were successfully achieved with very good yields using a TBAF-mediated cyclisation. The cleavage of the SMP group to cis-oxazolidin-2-ones failed until now in spite of different cleavage methods trials. The inositol-transferase-inhibitors Galbonolide A and B were chosen as attractive targets for total synthesis because of their high biological activity and exciting molecular architecture. The retrosynthetic concept shows high flexibility and access to all enantio- and diastereoisomers with the possibility of analogue syntheses. All retrosynthetic trials are based on the idea of selective and atomeconomic synthesis including avoidance of protecting groups, short synthetic pathways to key building blocks, and convergent reaction series. The successful reaction pathway included as key steps an enzymatic reduction, Takai-, Wittig-, Stille- and ditin-Stille-reaction, an Enders-alkylation and a 1,2-addition using directing groups. So far two of the four stereogenic centers and all double bonds were combined in a ten-membered building block of the 14-membered ring structure of the Galbonolides without restriction in flexibility. Barium-mediated asymmetric allylation to ketons was achieved for the first time with addition of allyl chloride to enantiomeric keto esters. The synthesis of a five-membered lactone with good yield, and after isolation with good diastereo- and enantiomeric excesses resulted in the idea of synthesising 4’-epi-2’-desoxynucleosides, which is now under progress.
Degree
thesis:*- Grantor dc:publisher
- Publikationsserver der RWTH Aachen University
- Year dc:date
- 2002
Author and committee
dc:creator, dc:contributor.*- Author dc:creator
-
- Ridder, André
- Contributors dc:contributor
-
- Enders, Dieter
Subjects
dc:subject × 7Rights
dc:rights- Statement dc:rights
-
- info:eu-repo/semantics/openAccess
- Language dc:language
- ger
Identifiers
dc:identifier.*- OAI identifier oai:identifier
- oai:publications.rwth-aachen.de:60133