Stereoselective synthesis of semiochemicals related to pine sawflies

Abstract: This thesis describes the stereochemistry and charactericsof (–)-1,6-germacradien-5-ol, isolated from the larvaldefence substance of the pine sawflyNeodiprion sertiferand from the needles of Scots pine,Pinus sylvestris. The conformational behaviour of thissesquiterpene alcohol was investigated by molecular mechanicsstudies (MM2) and NMR. The absolute configuration at the twostereogenic centres was established as (5S,8S), after NOE measurements and chemical transformationinto (–)-α-cadinol and 1-endo-bourbonanol. Our studies towards a stereoselectivetotal synthesis of (–)-1,6-germacradien-5-ol using ringclosing metathesis (RCM) is also reported. However, allattempts to prepare this germacrene alcohol and other1,6-cyclodecadien systems using RCM failed.Pseudomonas cepacialipase (PCL) catalysed acylation ofprimary 2-methylalcohols with vinyl acetate is anenantioselective reaction. The enantioselectivity of PCLtowards a series of primary 2-methylalcohols were studied. Highenantiomeric ratios,E>100, were observed for2-methyl-3-aryl-1-propanols, where aryl is 2-thiophene,3-thiophene, 2-furan and phenyl. In contrast the selectivitywas rather low for other 3-substituted primary2-methylpropanols such as 3-alkyl and 3-cycloalkyl, E ≈10 - 20. When moving the thiophene ring closer or further awayfrom the stereogenic centre a dramatic decrease in E wasobserved. 2-Isopropyl-5-methyl-5-hexen-1-ol, a possiblebuilding block for the total synthesis of1,6-germacradien-5-ol, was also successfully resolved with PCL,E= 14.Keywords:defence substance, 1,6-germacradien-5-ol,Neodiprion sertifer,Pinus sylvestris, molecular mechanics, configuration,metathesis, RCM, stereoselective, kinetic resolution,transesterification, lipase,Pseudomonas, PCL, 2-methylalcohol, 2-isopropylalcoholenantioselective.