Synthesis of Polycylic Compounds Possessing Biological Activities by Novel Intramolecular Cascade Reactions

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Cascade reactions forming multiple bonds in a stereo- and regio-selective manner by one procedure is one of the most ideal process in organic synthesis. The cascade reaction is also called as domino and tandem reaction. We have already developed two types of cascade reactions, which are useful for natural products synthesis. Thus, the intramolecular double Michael reaction of a compound having two types of unsaturated carbonyl groups provides a ploycyclic compound fused to six membered ring possessing five stereogenic centers. On the other hand, the intramolecular Michael-aldol reaction of the keto unsaturated ester constructs a polycyclic ring system fused to four membered ring having four stereogenic centers. These cascade reactions could be carried out under five different conditions using lithium hexamethyldisilazide or combinations of Lewis acids and Lewis amines. They have various advantages due to both merits of intramolecular reaction and cascade reaction. In this project, we achieved following total syntheses of natural products possessing important biological(1) Synthesis of Indole Alkaloid, TacamonineTreatment of an indole derivative having an alpha, beta-unsaturated ester function at the C-2 position and an unsaturated amide group at the C-3 position with TBSOTf in the presence of triethylamine provided the indoloquinolizidine derivative. Synthesis of tacamonine was carried out in a facile manner from the product.(2) Synthesis of Sesquiterpenoids, Cedranediol and CedranoxideIntramolecular double Michael reaction of 5-substituted cyclopentenone gave tricyclo[5.2.1 .0^<1.5>]decane, which was converted into cedranediol and cedranoxide.(3) Synthesis of Sesquiterpenoid, CulmorineAn effective total synthesis of culmorine was accomplished via the intramolecular double Michael reaction of 4-substituted cyclopentenone as key step.