| Insects and related arthropods produce a variety of defensive chemicals, ranging from relatively mundane aliphatic acids to steroid derivatives and structurally complex alkaloids. Alkaloids from the ladybird beetles (order Coleoptera family Coccinellidae) are among the most interesting from the perspective of the synthetic chemist.;The pupae of some members of the genera Epilachna and Subcoccinella produce and secrete a family of macrocyclic alkaloids, some with unprecedented ring sizes of more than 200 members. An efficient, stereospecific synthetic route to several of these alkaloids was developed using enantiomerically-pure amino acids as chiral pool starting materials. Key features of the syntheses include (1) the formation of chiral tosylaziridines from readily available amino acids, (2) subsequent opening of the aziridine ring by organocuprate reagents, (3) a novel Wittig reaction of ozonides, and (4) macrocycle formation using Mukaiyama macrolactonization conditions. Subsequent derivatization and gas chromatographic comparison of the synthetic alkaloids with insect-derived macrocyles established the absolute stereochemistry of the natural materials.;A number of other coccinellid species contain members of a family of polycyclic alkaloids typified by hippodamine, the structure of which contains a continuous chain of thirteen carbon atoms arranged into three six-membered rings built around a central nitrogen. Among the more interesting compounds in this family are the "pseudo-dimeric" alkaloids found in Exochomus quadripustulatus, and Chilocorus cacti. These complex alkaoids represent a considerable synthetic challenge. One half of these structures has been synthesized in a previous study, but the production of a suitable coupling partner to complete the total syntheses remains an elusive goal. In the present study, work toward the production of a bicyclic medium-ring ketone which should be a versatile synthetic precursor in the formation of a number of polycyclic coccinellid alkaloids is presented. |
