Chiral building blocks for synthesis of pine sawfly sex pheromones Enantioselective Lipase Catalysed Acylations and Esterifications of Primary Alcohols and Acids and Synthesis of the Sex Pheromone of the Pine Sawfly Microdiprion pallipes
This thesis describes the development of new methods for thepreparation of enantiomerically pure methyl branched alkylcompounds and their use as building blocks in the synthesis ofstereoisomerically pure pheromones of pine sawflies.The high regioselectivity, enantioselectivity and activityof lipases in organic solvent in conjunction withenvironmentally compatible reaction conditions have madelipase-catalysed synthesis an attractive alternative toconventional synthetic methods in organic chemistry. The lipasefromPseudomonas cepacia(PCL) was used in kineticresolutions of primary 2- methylalcohols by acylation of thealcohols with vinyl acetate/vinyl butyrate. For alcoholsstudied, PCL showed moderate enantioselectivity(E= 10-20) towards 3-alkyl- or 3- cycloalkylsubstitutedprimary 2-methylpropanols, whereas 3-aryl-2-methyl-1-propanolswere accepted with high E-values(E>100).Esterification of substituted methylcarboxylic acids withprimary alcohols catalysed byCandida rugosalipase (CRL) was found to be anenantioselective reaction. In general, CRL showed highselectivity towards(S)-2-methylcarboxylic acids(E= 15-70) and also towards(R)-3-methylcarboxylic acids(E= 15-40). For substrates having a double bond located5-6 bonds from the carbonyl moiety a two-fold enhancement ofenantioselectivity value(E-value) was obtained compared to their saturatedanalogues,E? 15-25.Furthermore, the enantioselectivity of CRL towards a seriesof 3- to 8-methyldecanoic acids were studied. CRL surprisinglyshowed enantiorecognition for all of these acids within theE-value range of 2.3-68. Interestingly, whereas the lipaseshowed S-preference when the methyl group was situated ateven-numbered carbons, R-preference was observed for thesubstrates with the methyl group at odd-numbered carbons.In order to establish the stereoisomeric composition of thenatural sex pheromone of the pine sawflyMicrodiprion pallipes, all sixteen individual isomers of3,7,11-trimethyl-2-tridecanol (and their propionate esters)found in this species were synthesised in highdiastereoisomeric purities, 95.3-97.6%. The syntheses werebased on six enantiomerically pure building blocks, the fourstereoisomers of 1-lithio-2,6-dimethyloctane and the twoenantiomers ofcis-3,4- dimethyl-g-butyrolactone.Keywords:lipase,Pseudomonas cepacia,Candida rugosa, enantioselective, enantiomeric ratio,primary 2-methylalcohol, substituted-methylcarboxylic acid,pine sawfly,Microdiprion pallipes, sex pheromone,3,7,11-trimethyl-2-tridecanol, stereoisomer.
School:Kungliga Tekniska högskolan
Source Type:Doctoral Dissertation
Keywords:lipase; Pseudomonas cepacia; Candida rugosa; enantioselective; enantiomeric ratio; primary 2-methylalcohol; substituted-methylcarboxylic acid; pine sawfly; Microdiprion pallipes; sex pheromone; 3; 7; 11-trimethyl-2-tridecanol; stereoisomer
Date of Publication:01/01/2000