Hisao Takayanagi

Isolation of sex pheromones of the american cockroach by monitoring with electroantennogram responses

Abstract Two sex pheromones of the American cockroach were isolated from female faeces and from the filter paper shelters on which 2130 adult females had been reared. The isolation was achieved by a rapid and accurate monitoring method using an electroantennogram technique with an adult male antenna. The two pheromones were suggested to be periplanone-A and periplanone-B by their mass spectra and strong activities in behavioural assay tests. The quantities of periplanone-A and periplanone-B were estimated to be 6.8 and 1.5 μg, respectively, by gas chromatographic analysis.

Stereo- and enantioselective total synthesis of sarcophytol-A

Abstract The first total synthesis of sarcophytol-A, a biologically important marine cembranoid, was achieved in a highly stereo- and enantioselective manner.

Z-selective formation of trisubstituted α,β-unsaturated nitrile by the Horner-Emmons reaction

Conditions which allow the Horner-Emmons reaction of phosphononitrile to proceed Z-selectively were clarified. The generality and usefulness of the procedure were demonstrated by an application to a stereoselective synthesis of plaunotol (9).

Total syntheses of both enantiomers of sarcophytols A and T based on stereospecific [2,3]Wittig rearrangement

Both enantiomers of sarcophytols A (1) and T (2), cembranolide diterpenes isolated from a soft coral, were synthesized from a common chiral intermediate, obtained by bakers yeast reduction, using a stereospecific [2,3]Wittig rearrangement as the key step.

Sex pheromonal activity of (+)-trans-verbenyl acetate and related compounds to the american cockroach,Periplaneta americana L.

The sex pheromone mimic of the American cockroach, (+)-trans-verbenyl acetate, and 67 synthesized analogs were tested for sex pheromonal activity using males of the cockroach. Only three esters in addition to the original (+)-trans-verbenyl acetate exhibited activity. (+)-trans-Verbenyl propionate and (+)-verbanyl acetate in particular showed stronger activity than the original mimic. None of the other analogs caused a response at the 1-mg level. The lower threshold levels at which even the most active analogs showed activity (0.02 mg) were many orders of magnitude higher than that of the natural pheromone, periplanone-B (10−8 mg). From the structure-activity relationships, important structural factors for sex pheromonal activity in the original mimic were discussed.

A ketal Claisen rearrangement for α-ketol isoprene unit elongation: application to a practical synthesis of sarcophytol A intermediate

A new ketal Claisen rearrangement using the ketal 10 for the isoprene unit elongation which affords terminal α-ketol terpenoid is presented. Its efficiency is demonstrated by successful transformation of the product of this reaction, the α-ketol 20, into 2, the acyclic precursor of sarcophytol A total synthesis, by two alternative routes via the β,γ-unsaturated aldehyde 24 and the allylic alcohol 28.

Structural significance of the geminal-dimethyl group of (+)-trans-verbenyl acetate, sex pheromone mimic of the American cockroach.

The significance of the geminal dimethyl group at C-6 of (+)-trans-veibenyl acetate (Ib), a sex pheromone mimic of the American cockroach, was investigated. Our interest was first directed to eliminating either methyl group of the geminal dimethyl group. Consequently, alcohols (IIIa and IVa) possessing a monomethyl group at C-6 were successfully obtained. Acetate (IVb) and propionate (IVc) of alcohol (IVa) possessing only a C-9 methyl group induced sex pheromonal activity at the 0.5 (IVb) and 0.02 mg (IVc) dose levels, respectively, while acetate (IIIb) of a alcohol (IIIa) with only C-8 methyl group was inactive. Alcohol (Va), which has an ethyl group at the C-6 instead of C-9 methyl, was also synthesized and converted into its acetate (Vb), which showed no activity. From these results, the significance of the dimethyl group is discussed relative to spatial requirements of the molecule for the receptor space. The M/F ratio in EAG was also evaluated for the synthesized esters. The M/F ratio index represented well the potency of pheromonal activity.

Structural significance of the alkyl substituent at the C-4 of (+)-trans-verbenyl acetate in sex pheromonal activity of the American cockroach.

The significance of the alkyl group at the C-4 of (+)-trans-verbenyl acetate, which is the sex pheromone mimic of the American cockroach, was investigated. Seven alcohols possessing an ethyl, propyl, or dimethyl group at this position of the 6,6-dimethylbicyclo[3.1.1]heptane skeleton were synthesized and evaluated by behavioral assay. All of the alcohols were inactive, while three of four acetates of the 2α-alcohols induced sexual behavior in male cockroaches at the 0.02 or 0.5 mg dosage level, either of which is many orders of magnitude higher than the threshold level of the natural sex pheromones (10−8 mg). Among the acetates, the compounds with a methyl group or an α-oriented ethyl group at C-4 showed the highest activity. The results are discussed in terms of spatial requirements of the molecules for interactions with the receptor.

Chiral influence of sex pheromonal substances on responses of the male American cockroach

In order to elucidate the roles of optical enantiomers of sex pheromonal substances of the American cockroach, behavioral assays with a single enantiomer and with mixtures of enantiomers of sex pheromone mimics were carried out. Inactive enantiomers [(−)-enantiomers] had no influence on the potency of enantiomers active as sex pheromones [(+)-enantiomers]. By analysis of the results from EAG recordings with single and mixed sample of the enantiomers, it was confirmed that (−)-enantiomers did not react with the sex pheromone receptors which are responsive to (+)-enantiomers.

Alternative synthetic route to the cembrene skeleton

The cembrene derivative (VI; Z = SO2Ph) has been prepared by coupling of the geranyl units (I) and (II) to give the seco-cembrene derivatives (IIIa) or (IIIb), followed by reduction (IIIa) or hydrolysis (IIIb), conversion into the bromide, (V; Y = Br), and ring closure with lithium di-isopropylamide.