Een modelsynthese voor momilactonen : onderzoek naar de totaalsynthese van 9betaH-pimara-7,15-dienen

This thesis describes investigations into the total synthesis of momilactones, germination inhibitors and phytoalexins isolated from rice. These compounds possess a Δ ^7,8 -pimaradiene type skeleton with an unusual trans-syn ring-arrangement (figure 1).In chapter 1 a survey is given of the momilactones and the other hitherto known trans-syn pimaranelactones, with emphasis on their structures, biosynthesis and physiological activities.Chapter 2 is devoted to a literature survey of synthetic studies towards trans-syn(-cis) perhydrophenanthrene systems. The chemical reactivity of trans-syn pimaranelactones is also discussed.In chapter 3 the results are presented of a synthetic investigation, based on the Diels-Alder reaction depicted in scheme 1.This approach provided a total synthesis of Δ ^8,9 -pimaradiene and Δ ^8,9 -sandaracopimaradiene. However, attempts to isomerize the double bond to the desired Δ ^7,8 -position met with little success. We therefore turned our attention towards starting compounds bearing an oxo group on C-7, in order to utilize this group for the introduction of the Δ ^7,8 -double bond at a later stage.Using the work of W.L.Meyer and coworkers as a starting point, we stereospecifically synthesized a trans-syn-cis perhydrophenanthrene system as outlined in scheme 2. This part of the investigations is described in chapter 4. Several ways for the stereospecific introduction of a second substituent on C-13 were investigated. our synthesis of compound 159 could probably have been elaborated further, but we chose to focus our attention on a more promising approach which is described in chapter 5.Our stereospecific synthesis of trans-syn-cis perhydrophenanthrene systems, which forms the subject of chapter 5, is based on the stereospecific Diels-Alder reaction depicted in scheme 3 and culminates in the succesful synthesis of model compound 122. Initially we used 2- trimethylsilyloxybutadienes as diene components, but severe hydrolysis problems were encountered with the resulting adducts. These problems were effectively overcome by using diene 190. The adduct possesses a regiospecific silylenolether system which can be alkylated at C-13. Adduct 191 could be deformylated and stereoselectively reduced to the alcohol 197 leaving the t-butyldimethylsilylenolether intact. Two possible synthetic routes were then investigated.Alkylation of compound 199 with 2-ethoxy-1,3-dithiolan surprisingly only gave one thiolanyl compound (200) which proved to have the thiolanylgroup in the α-position. Reduction and hydrolysis of this compound gave the hydroxyaldehyde 205. However, during the Wittig reaction of the latter compound, equilibration occurred via (retro-)aldol reaction, resulting in considerable epimerization at C-13. Only a small amount of α-vinylproduct was found. Oxidation and Wolff-Kishner reduction finally afforded the model compound 122.Alkylation of compound 201 with 2-ethoxy-1,3-dithiolan yielded stereospecifically the β-thiolanyl product, as could be expected for steric reasons. This product was elaborated further as shown. Here, too, a (retro-)aldol reaction occurred during the Wittig reaction of compound 225, resulting in both hydroxy-epimers of the β-vinyl alcohol. No α-vinylproduct could be detected in this case. This concluded the stereospecific synthesis of compound 122.X-ray crystallography of thiolanyl-compounds 200 and 219 and ¹³ C-NMR spectroscopy were used to establish the stereochemistry of a number of reaction products, especially concerning the configuration at C-13. Details of these measurements can be found in chapter 6.Finally, in chapter 7, the results of the investigations are summarized and evaluated in relation to the total synthesis of momilactones.