Gerrit A. Stork

The synthesis of mono- and dihydroxy aromadendrane sesquiterpenes, starting from natural (+)-aromadendrene-III

Abstract The monoalcohols (−)-globulol ( 2 ), (−)-epiglobulol ( 3 ), (−)-ledol ( 4 ), and (+)-viridiflorol ( 5 ) were synthesized from (+)-aromadendrene ( 1 ). The cis-fused alloaromandedrone ( 14 ), the key intermediate used in the synthesis of 4 and 5 , was obtained from the trans-fused apoaromadendrone ( 13 ) via a selective protonation of the thermodynamic enol trimethylsilylether 15 . After hydroxylation of the tertiary C11 of 13 with RuO 4 , (+)-spathulenol ( 6 ), (−)-allospathulenol ( 7 ), and the aromadendrane diols 8 – 11 could be prepared. Compounds 2 – 11 were tested for antifungal properties, but their activity was only moderate.

The synthesis of (-)-kessane, starting from natural (+)-aromadendrene-II

Abstract Starting from the readily available chiral synthon 5 the sesquiterpene ether (−)-kessane (1) can be synthesized in a 9 steps reaction sequence in an overall yield of 43%.

The conversion of natural (+)-aromadendrene into chiral synthons-I.

Abstract (-)-Apoaromadendrone (3) can be obtained easily in large quantities from (+)-aromadendrene which is the main constituent in a commercially available distillation tail of the oil of Eucalyptus globules. Acid catalyzed selective cleavage of the C3-C4 bond of the cyclopropane ring in 3 gave (-)-isoapoaromadendrone(9) in high yield. The regioselectivity of the cyclopropane ring opening was proved by NMR spectroscopy in combination with chemical transformations. Ozonolysis of 9 afforded the keto alcohol 14 which is a suitable chiral intermediate for the syntheses of guaianes and guaianolides.

Enantioselective Synthesis of Functionalised Decalones by Robinson Annulation of Substituted Cyclohexanones, Derived from R-(−)-Carvone

Abstract The copper catalysed conjugate addition of methyl magnesium iodide to cyclohexenones and trapping of the enolate as its trimethylsilyl enol ether, followed by a trityl hexachloroantimonate (TrSbCl6) catalysed Mukaiyama-reaction, was applied to R-(−)-carvone. This proved to be an efficient method for the preparation of C-2, C-3 functionalised chiral cyclohexanones. These compounds were converted into their α-cyano ketones, which were submitted to Robinson annulation reactions with methyl vinyl ketone. The scope and limitations of these annulations were investigated. A series of highly functionalised chiral decalones were obtained that can be used as starting compounds in the total syntheses of enantiomerically pure clerodanes.

Enantioselective synthesis of highly functionalised cyclohexanones starting from R-(−)-carvone

Copper (I) catalysed conjugate addition of methylmagnesium iodide to R-(−)-carvone and trapping the enolate as its trimethylsilyl enol ether, followed by a trityl perchlorate (TrClO4) catalysed Mukaiyama-aldol reaction, is an efficient method for the preparation of highly functionalised cyclohexanones which can be used as starting compounds in the total syntheses of enantiomerically pure clerodanes.

SYNTHESIS AND INSECT ANTIFEEDANT ACTIVITY OF 2-SUBSTITUTED 2,3-DIHYDROFURAN-3-OLS AND BUTENOLIDES. (PART II)

Abstract The introduction of a hydroxy group at C-13 of the clerodane skeleton is proposed as a strategy to potentially increase the antifeedant activity of simple analogs. This idea is applied to clerodane analogs with furan or butenolide type sidechains and therefore syntheses were developed for several types of 3-alkyl-substituted butenolides, 3-alkyl-substituted-3-hydroxybutenolides and 3-hydroxytetrahydrofuran derivatives. The antifeedant activity was tested on 5th instar larvae of Pieris brassicae .

Recent developments in the synthesis of drimane and lactarane sesquiterpenes

Abstraa: Several new methods for the construction of ene-dialdehyde functionalities and for the regioselective annulation of butenolides were developed and applied in the synthesis of drimane and lactarane sesquiterpenes. Optically active drimanes were synthesised starting from S-(+)and R-(-)-cawone. A new development in this approach starts with a conjugate addition of cyanide to the enone in carvone, followed by an annulation reaction. Base-induced and directed reactions of substituted trans perhydronaphthalene-1,4diol monosulfonate esters in apolar solvents provide an effective route to cis perhydroazulene systems. The rearrangement can be directed towards intramolecular ether formation. Based on this approach a total synthesis of lactaranes is under investigation.