Total synthesis of all stereoisomers of eudesm-II-en-4-ol

R.P.W. Kesselmans

Research output: Thesisinternal PhD, WU


<p>In this thesis the total synthesis of all stereoisomers of eudesm-11-en-4-ol e.g. selin-11-en-4α-ol <strong>I</strong> , intermedeol <strong>II</strong> , neointermedeol <strong>III</strong> , paradisiol <strong>IV</strong> , amiteol <strong>V</strong> , 7- <em>epi</em> -amiteol <strong>VI</strong> , 5- <em>epi</em> -neointermedeol <strong>VII</strong> , and 5- <em>epi</em> -paradisiol <strong>VIII</strong> is described.<p>The natural occurrences and the difficulties encountered in the structural elucidation of these eudesmanes are described in chapter 1. The eudesm-11-en-4-ols occur in a wide range of plant species, some of which are used in medicine, or as insect repellent. However, the most spectacular occurrence of eudesm-11-en-4-ols is established in the secretion of termite soldiers. These secretions are used as chemical weapons to defend the termite colony.<p>In chapter 2 the strategies used in eudesmane syntheses are reported. The first part of this chapter deals with general approaches to the eudesmane skeleton. This part is organized in sections, each dealing with a number of methods under a common heading i.e. annulation, cycloaddition, intramolecular cyclization reactions, and transformations of natural sesquiterpenes. The second part of the chapter describes the reported total syntheses of intermedeol <strong>I</strong> , neointermedeol <strong>III</strong> , paradisiol <strong>IV</strong> , and 5- <em>epi</em> -paradisiol <strong>VIII</strong> . These syntheses proceed in low overall yields because of the occurrance of complex product mixtures.<p>The lack of spectroscopic and chromatographic data 6 for identification, the interesting biological properties, and the availability of a good synthetic plan has been the reason for this investigation (Chapter 3). Starting from enone <strong>101</strong> , a large scale synthesis of the diones <strong>95</strong> and <strong>96</strong> has been developed as is described in chapter 4. The <em>trans</em> -fused dione <strong>95</strong> was transformed into the cisfused dione <strong>96</strong> by treatment with trimethyl orthoformate and a catalytical amount of acid in CH <sub><font size="-1">3</font></sub> OH. This transformation allows full stereocontrol on the C-5 bridgehead position.<p>An efficient method for the synthesis of the octahydro-8-hydroxy-4a,8-dimethyl-2(1 <em>H</em> )-naphthalenones <strong>97-100</strong> , which are suitable intermediates in the total synthesis of <em>trans</em> - and <em>cis</em> -fused 4-hydroxyeudesmane sesquiterpenes is reported in chapter 5. Starting from the <em>trans</em> -fused dione <strong>95</strong> the corresponding hydroxy ketones <strong>97</strong> and <strong>98</strong> could be easily prepared. The <em>cis</em> -fused hydroxy ketones <strong>99</strong> and <strong>100</strong> were synthesized starting from the dione <strong>96</strong> . Protection of the C-7 carbonyl function of <strong>96</strong> as its <em>dimethyl a</em> cetal followed by treatment with CH <sub><font size="-1">3</font></sub> Li gave the hydroxy ketone <strong>100</strong> . On the other hand, protection of the C-7 carbonyl function of <strong>96</strong> as its <em>ethylene</em> acetal and subsequent treatment with CH <sub><font size="-1">3</font></sub> MgI afforded the hydroxy ketone <strong>99</strong> as the main product. NMR studies revealed that <strong>100</strong> exists predominantly in the steroid conformation and that <strong>99</strong> exists exclusively in the nonsteroid conformation.<p>The syntheses of the natural occurring (±)-selin-11-en-4α-ol <strong>I</strong> , (±)-intermedeol <strong>II</strong> , (±)-neointermedeol <strong>III</strong> , (±)-amiteol <strong>V</strong> , and the four remaining stereoisomers (±)-paradisiol <strong>IV</strong> , (±)-7- <em>epi</em> -amiteol <strong>VI</strong> , (±)-5- <em>epi</em> -neointermedeol <strong>VII</strong> , (±)-5- <em>epi</em> -paradisiol <strong>VIII</strong> , which not yet have been discovered in nature, are described in chapter 6. In addition the related (±)-evuncifer ether <strong>128</strong> has been prepared. The syntheses in this chapter started from the hydroxy ketones <strong>97-100</strong> . The reaction sequence employed for the synthesis of <strong>I</strong> , <strong>III</strong> , <strong>V</strong> , and <strong>VIII</strong> involved Wittig reaction, oxidative hydroboration, oxidation, equilibration, and olefination. For the synthesis of <strong>II</strong> , <strong>IV</strong> , <strong>VI</strong> , and <strong>VII</strong> the interim equilibration step was omitted. The oxidative hydroboration was the key step in these syntheses.<p>The conformational behavior of the cis-fused stereoisomers of eudesm-11-en-4-ol has been investigated using NMR and conformational energy calculations (MM2) and is reported in chapter 7. In addition, the conformational analysis of most <em>cis</em> -fused intermediates in the synthesis to <strong>V</strong> and <strong>VI</strong> are studied.<p>Kovats indices and mass-, GC/FTIR-, <sup><font size="-1">1</font></SUP>H NMR-, and <sup><font size="-1">13</font></SUP>C NMR data were collected for all eight stereoisomers of eudesm-11-en-4-ol in chapter 8. Differences in Kovats indices, mass spectral data, and GC/FTIR of the various isomers on one side, and <sup><font size="-1">1</font></SUP>H NMR and <sup><font size="-1">13</font></SUP>C NMR on the other, are shortly discussed. In this way other investigators may be able to identify these common essential oil constituents more reliably in future, either without isolating them (by Kovats indices, GC/MS, and GC/FTIR) or after isolation (by NMR).
Original languageEnglish
QualificationDoctor of Philosophy
Awarding Institution
  • de Groot, Æ., Promotor, External person
  • Wijnberg, J.B.P.A., Promotor
Award date18 May 1992
Place of PublicationS.l.
Publication statusPublished - 1992


  • terpenoids
  • synthesis

Fingerprint Dive into the research topics of 'Total synthesis of all stereoisomers of eudesm-II-en-4-ol'. Together they form a unique fingerprint.

Cite this