Podolactonen : een synthetische studie

A.J.G.M. Peterse

Research output: Thesisinternal PhD, WU

Abstract

This thesis describes an investigation on the total synthesis of physiologically active nor-diterpene dilactones, called Podolactones.
In Chapter I a survey is given of the known Podolactones with the emphasis on their structure, biogenesis and biological activities.
Chapter II deals with the chemical reactivity of the isolated Podolactones and with the two reported total syntheses of the Podolactone LL-Z 1271 α. Also a strategy for the synthetic investigation described in this thesis is outlined.
The construction of functionalized decalines, which can be further elaborated into Podolactones, is the subject of Chapter III.
The synthesis of these bicyclic compounds is based on a Dieckmann cyclisation of a saturated-unsaturated diester, which is obtained from a 2,2-disubstituted cyclohexanedione-1,3 by addition of lithiumethoxyethyne and a subsequent Meyer Schuster rearrangement of the formed ethynylcarbinol. Careful control of the reaction conditions results in a stereoselective, high-yield formation of the necessary intermediates.
Several approaches to tricyclic γ-lactones from bicyclic precursors are discussed in Chapter IV.
Lactonisation of the 6-bromo-, 6-hydroxy- and 3,6-dihydroxyesters is investigated. The alkylation and reduction of the 6-hydroxyester and derivatives revealed interesting substituent effects. In the reduction of the 6-hydroxyester with lithium in liquid ammonia a strong temperature dependence was observed as well. Reduction at -78°C yields selectively an ester with a cis ringjunction, while at -33°C not only a trans ringjunction is established, but also a γ-lactone is formed. Moreover addition of methyliodide to the intermediate anion results in the formation of a C(4)-methylated γ-lactone. The residual carbonyl group
at C(3) is protected as a benzoyl- or β-methoxyethoxymethyl-enolether.
A model study for the construction of the BC-ring system of Podolactones can be found in Chapter V.
After conversion of cyclohexanones into the corresponding a-butylthiomethylenecyclohexanones, addition of lithiumethylacetate and a Hg ++ -assisted hydrolysis results in γ-formylesters, which can be transformed into δ-substituted δ-lactones by reaction with organolithium reagents.
This annellation method is applied to both mono- and bicyclic model compounds. The investigations on model compounds also resulted in the synthesis of the fully functionalized ring B of the potent antifeedants Warburganal and Muzigadial.
Finally in Chapter VI an evaluation of the results in relation to the total synthesis of Podolactones is given.

Original languageDutch
QualificationDoctor of Philosophy
Awarding Institution
Supervisors/Advisors
  • de Groot, Æ., Promotor, External person
Award date9 Nov 1979
Place of PublicationS.l.
Publication statusPublished - 1979

Keywords

  • diterpenoids
  • essential oils
  • sesquiterpenes
  • sesquiterpenoids
  • terpenoids

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