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.
|Qualification||Doctor of Philosophy|
|Award date||8 Jun 1984|
|Place of Publication||Wageningen|
|Publication status||Published - 1984|
- plant protection
- essential oils