Chemoenzymatic methods for the syntesis of pine sawfly sex peromones

Abstract: This thesis describes the syntheses of pine sawfly sexpheromones via two synthetic routes. The preparation ofenantiomerically pure building blocks for these is alsodescribed.Lipase catalysed methods were developed for either theresolution or desymmetrisation of building blocks. In addition,selective lipase catalysed acylation was investigated as amethod for the preparation of stereoisomerically pure pheromonecomponents.Parameters influencing the kinetic resolution byesterification of 2-methylalkanoic acids catalysed byCandida rugosalipase in organic solvents wereinvestigated. Reproducible enantiomeric ratios (E-values) and reaction rates were obtained by control ofthe water activity both for small scale and preparative scalereactions. Low concentration and long chain length of then-alcohols co-substrate enhanced the selectivity andsimplified the work up procedure. Large-scale esterification ofracemic 2-methyloctanoic acid catalysed byCandida rugosalipase furnished (R)-2-methyloctanoic acid in high yield and afterreduction of the ester product, (S)-2-methyl-1-octanol in a moderate yield, respectively.Both were virtually enantiopure. These building blocksfunctioned as precursor derivatives in the syntheses of theeight possible stereoisomers of 3,7-dimethyl-2-tridecanol,which were used for the identification of the pheromone ofDiprion pini.Either high enantioselectivity or diastereoselectivity wasobtained in lipase catalysed kinetic acylations of a number oferythro- andthreo-3-methyl-2-alcohols, which were needed for theidentification of the pheromones, of several pine sawflyspecies.The possibility to resolve an alternative synthetic buildingblock, useful for the synthesis of pine sawfly pheromones, wasexplored. Thus, (meso/ ± )-2,6-dimethyl-1,7-heptanedioic acid wasesterified withn-butanol catalysed byCandida rugosalipase. Using this method,enantiomerically pure (2R,6R)-2,6-dimethyl-1,7-heptanedioic acid could be obtained,albeit in a low yield.Keywords: pheromone syntheses, pine sawfly,Diprion pini,Gilpinia pallida,Candida rugosa, lipase, kinetic resolution, wateractivity, 2-methylalkanoic acids, 2,6-dimethyl-1,7-heptanedioicacid, 3-methyl-2-alcohols, transesterification,enantioselectivity