First total synthesis of the sex pheromone of the oleander scale Aspidiotus nerii: An unusual sesquiterpenic functionalized cyclobutane

The first total synthesis of the sex pheromone of the oleander scale Aspidi otus nerii (5), an economically important polyphagous pest, is described. T he synthesis is based on a stereocontrolled and completely regioselective i ntramolecular exo-cyclization of cis-epoxynitrile 9 to afford cyclobutane a lcohol t-10 stereoselectively. Introduction of the unusual 4-methylpent-4-e nyl group onto the cyclobutane skeleton was effected through Wittig reactio n of aldehyde 17b with the bulky ylide 3,3(ethylenedioxy)butylidenetripheny l-phosphorane. This process requires protection of the primary hydroxy grou p of 10 with a nonbulky protecting agent, like methoxymethyl (MQM) but not tetrahydropyranyl (THP), as confirmed by molecular modelling studies. After selective transformations to manipulate the three acid-sensitive protectin g functionalities present, that is, the tert-butyl-dimethylsilyl (TBDMS), e thylene acetal, and MOM groups, compound 5 was obtained in 26.4% overall yi eld from t-10b. In a different approach, complete cleavage of these protect ing groups in 19b furnished keto diol 31, which after regioselective acetyl ation of the primary alcohol and Wittig reaction afforded acetate 5 in 21.4 % overall yield from t-10b. The synthetic material exhibited spectroscopic features identical to those of the natural material and showed remarkable b iological activity in field tests.