Kentaro Okada

Behavioral responses of malePeriplaneta americana L. to female sex pheromone components, periplanone-A and periplanone-B.

Bioassays were performed on malePeriplaneta americana L. using synthetic (−)-periplanone-B (P-B) and Hauptmanns (−)-periplanone-A (P-A), and their mixtures at various ratios to estimate the roles of both periplanones for the sexual communication of the species. Both P-A and P-B elicited qualitatively the same responses, such as antennal movement, rapid locomotion, wing raising, and homosexual behavior of male cockroaches, but the threshold of the pheromone activities for P-B was two orders of magnitude lower than that of P-A. Neither synergistic nor inhibitory but only a simple integrated effect on the responses was observed when mixtures of P-A and P-B were applied.

Behavioral and electroantennogram responses of periplanone analogs

The biological activities of synthetic periplanone analogs, including four candidates of periplanone-A (P-A), were evaluated by behavioral and electroantennogram (EAG) assays. Among 16 periplanone analogs, six compounds evoked pheromonal activity from the male American cockroaches. The threshold dosages of these biological active analogs were 10–105 times lower than that of the known periplanone mimic, germacrene-D. The conformation required for eliciting the pheromonal activity is discussed in terms of the structure-activity relationship of these analogs. Hauptmanns P-A elicited the strongest pheromonal activity among four candidates of P-A in our bioassay, suggesting that Hauptmanns P-A is a natural P-A produced from female cockroaches.

Olfactory responses to the sex pheromone component and its behavioural inhibitor in the male cigarette beetle, Lasioderma serricorne

Abstract Electroantennogram and single sensillum recordings were performed on the male cigarette beetle, Lasioderma serricorne , antennae. Strong antennal responses were elicited by not only natural sex pheromone component (4S,5S,7S)-serricornin (SSS-serricornin) but also non-natural behavioural inhibitor, (4S,5S,7R)-serricornin (SSR-serricornin). In the case of mixture application of the SSS- and SSR-serricornin, integrated electroantennogram responses were observed. Single sensillum recording from male flagella sensilla showed that the majority of basiconic type sensilla responded to the behavioural inhibitor as well as to the sex pheromone. However, a few of them responded only to the inhibitor. The behavioural inhibitory action of SSR-serricornin toward the SSS-serricornin results from central integration of the information from separate receptor cells rather than blockage at the peripheral receptors.

Synthesis of a simple analog of periplanone-B

The synthesis of a simple analog of periplanone-B with high biological activity is described mainly on the examination of the conformational property of the key intermediate 10-t-butoxy-6-methyldeca-2,6-dienone by molecular mechanics calculation and dynamic NMR spectroscopy

X-ray crystallographic and NOE studies on the conformation of periplanones and their analogues

The structure of periplanone-A was established by X-ray crystallographic analysis. In comparison of the X-ray and 1H NMR data with those of periplanone-B, it was shown that periphanone-A and -B adopt essentially the same conformation. The epoxy epimer of periplanone-A has l04-times lower biological activity than periplanone-A, and NMR analysis indicated that the molecule exists in a mixture of different conformers. The conformation of the regioisomer, in which the carbonyl and epoxy groups are transposed, was analysed by X-ray crystallography and 1H NMR spectroscopy. It is highly biologically active, and the conformation of the germacranoid skeleton was shown to be almost identical with that of periplanone-A. Simplified analogues and germacrene-D had relatively lower activity. NOE Experiments on these compounds suggested the conformational resemblance of their germacranoid skeletons with those of periplanone-A and -B.

Combined molecular mechanics (MM2) and molecular orbital (AM1) study of periplanone-B and analogues. Evaluation of biological activity from electronic properties and geometries

Combined molecular mechanics (MM) and semiempirical molecular-orbital (MO) calculations have been applied to the investigation on the conformational and electronic properties of periplanone-B (1), a major component of the sex pheromone of American cockroach, and structurally related analogues 2, 3, 4 and 5. In the first step, the geometries of conformers of 1–5 were obtained by MM2 combined with a new algorithm for exhaustive generation of ring conformations, CONFLEX2, and an additional set of MM2 force-field parameters. The global minimum (1A) of the natural pheromone populates predominantly and is superimposable on the X-ray structure. Minor conformers 1B and 1C correspond to the rotamers at the isopropyl group of 1A. The global minimum of the analogue 2 was identified to have the structure 2A, which agrees well with the X-ray data. The structural comparison of the stable conformers of the analogues 2–5 with 1A revealed similar ring conformations in the most stable conformers of 2, 3 and 4, and the third one of 5. These results suggest that the ring structure characteristic of the conformer 1A and the conformer populations must be a significant factor in the biological activity of these analogues. In the next step, the electronic properties were calculated by the semiempirical MO (AM1) method. A significant correlation is found between the biological activity and one of the unoccupied frontier orbitals which is localized around C1–C10–C9 including the carbonyl and spiro-epoxy groups. A newly defined effective frontier parameter: EF(N)(s), which regards the orbital electron density, orbital energy, and ring conformation is found to correlate well with the biological activity of these analogues.

Conformational analysis of serricornin : application of molecular mechanics calculations to stereochemical assignment of serricornin, sex pheromone of cigarette beetle (Lasioderma serricorne F.)

Conformational analysis using molecular mechanics (MM) was performed for a determination of the stereochemistry of serricornin, the sex pheromone of the cigarette beetle (Lasioderma serricorne F.). An exhaustive conformational analysis using MM2 calculations with algorithms for covering torsional energy surfaces of flexible molecules furnishes coordinates and steric energies of all local energy minimum conformers of serricornin, both acyclic and the corresponding cyclic forms. These coordinates gave angles required for the calculation of vicinal H/H coupling constants (3JHHs) of each energy minima by Altonas modified Karplus equation. The Boltzmann distributions of all local energy minima were calculated from their steric energies to furnish populations of each energy minimum conformer. Populationweighted averaged3JHHs of four enantiomeric pairs, (S*,S*,S*)-, (S*,S*,R*)-, (S*,R*,S*)-, and (R*,S*,S*)-serricornins were calculated from the data above. The observed3JHHs of the naturally occurring serricornin, both acyclic and cyclic forms, are fitted best to calcd.3JHHs of (4S*, 6S*, 7S*)-acyclic and (3S*, 5S*, 6S*)-cyclic serricornin, respectively, among those of four enantiomeric pairs of serricornin.

Conformational analyses of periplanone analogs by molecular mechanics calculations

Conformational parameters of pheromonally active analogs (1 and 2) of periplanones, the sex pheromones of the American cockroach, were investigated by molecular mechanics calculations. They existed in several conformers with small energy differences. These results were supported by NMR analysis. The structural features of the conformers of the analogs were compared with X-ray structures of periplanones.