The asymmetric syntheses of all the known defense alkaloids of the ant Tetraponera sp. tetraponerines T-1 to T-8 have been accomplished in five or six steps with 20-45% overall yields. The synthesis involved in the cross-condensation of (R)-piperidin-2-ylacetaldehyde with 4-aminobutyraldehyde which upon quenching by cyanide ion gave a stable tricyclic amino nitrile 3 with both a high yield and complete diastereoselectivity. This amino nitrile is the common precursor of four tetraponerines. A similar synthesis using (R)-pyrrolidine-2-ylacetaldehyde provided the tricyclic amino nitrile 2 precursor of the four other tetraponerines.Ants often use powerful defensive stings; although most of the venoms are of proteinic nature, some of them consist of alkaloids. This is the case for some Myrmicinae species as solenopsis or monomorium genus whose venoms contain dialkylated-piperidine, -pyrrolidine, or -indolizidine derivatives. 1 All these substances exhibit interesting insecticide properties. It was reported in 1988 by Braeckman, Daloze, and co-workers that the venom of pseudomyrmecine ants Tetraponera sp. consists of eight toxic alkaloids with an original tricyclic structure and which have been named tetraponerine-1 to tetraponerine-8 (T-1 to T-8). 2 Among these toxic substances, the structure and the relative configuration of the major component, tetraponerine-8, has been established by X-ray diffraction analysis. 2b Although erroneous structures were first published for T-3, T-5, T-6, and T-7, 2a very recently reported studies 3 fully established that the structures of tetraponerines, as deduced from their spectroscopic characteristics together with syntheses (T-5 and T-6) 3a and X-ray analysis (T-8), 2b are those represented in Figure 1. A doubt remains for the structures of T-1 and T-2 which were isolated in very small amounts, and indeed no NMR data have been reported for these compounds.The unprecedented tricyclic skeleton along with the interesting insecticidal activities of the tetraponerines (LD 50 ) 2 × 10 -9 mol/ant mg 2b ) have made them attractive targets for total synthesis. Indeed, very soon after their isolation, a total synthesis of the racemic form of the major alkaloid (+)-tetraponerine-8 was published by Merlin et al., 4 and its first asymmetric total synthesis was accomplished by our group. 5 Other total syntheses of (()-T-8 have also appeared 6 as well as those of (()-T-4, 6b (()-T-5, (()-T-6. 3b An asymmetric synthesis of (+)-T-8 and (+)-T-7 was recently described. 3a Nevertheless, no synthesis of T-1 and T-2, nor asymmetric synthesis of T-4, T-5, and T-6 has yet been accomplished.The asymmetric synthesis of (+)-T-8, described in a preliminary report, 5 enabled us to determine the absolute configuration of the natural enantiomer as that depicted in Figure 1. The absolute configuration of T-3, T-4 and T-7 have been determined by circular dichroism. 3a From the recently revised structures, 3 it appears that the strategy we used for the asymmetric synthesis of T-8 5 would allow us to synthesize ...
