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Syntheses of eight stereoisomers of methyl norchrysanthemate, (1R)‐trans‐(Z)‐isomer and (1R)‐trans‐(E)‐isomer from (1R)‐trans‐chrysanthemic acid, and other six isomers from (+)‐3‐carene, are described.

(1R)-trans-Norchrysanthemic acid fluorobenzyl esters are synthesized and their structure-activity relationships are discussed. These esters show outstanding insecticidal activity against mosquitoes. In particular, the 2,3,5,6-tetrafluoro-4-methoxymethylbenzyl analog (metofluthrin) exhibits the highest potency, being approximately forty times as potent as d-allethrin in a mosquito coil formulation when tested against southern house mosquitoes (Culex quinquefasciatus). Metofluthrin also exhibits a significant vapor action at room temperature.

Synthesis of analogues of two compounds with known insecticidal activity, both of which contain a 3,3-dichloro-2-propenyloxy group, produced 2-(trifluoromethyl)-4-phenoxyphenyl 3,3-dichloro-2-propenyl ether, which had weak activity against lepidopterous larvae. Structural modifications around this lead compound led to the development of pyridalyl [Pleo, S-1812; 2,6-dichloro-4-(3,3-dichloroallyloxy)phenyl 3-[5-(trifluoromethyl)-2-pyridyloxy]propyl ether], which belongs to a new class of insecticides. Pyridalyl gives very good control of various lepidopterous and thysanopterous pests on cotton and vegetables, without phytotoxicity. It controls populations of Heliothis virescens F and Plutella xylostella (L) which are resistant to various currently used insecticides. It also produces unique insecticidal symptoms, so it may have a different mode of action from other existing insecticides. Pyridalyl is also less harmful than existing insecticides to various beneficial arthropods, so it should provide an important tool in IPM and insecticidal management programmes for the control of lepidopterous and thysanopterous pests. The first market introduction is expected in Japan and some Asian countries in the years between 2004 and 2005.

Some gallic esters have interesting effects on the feeding activity of Formosan subterranean termites (Coptotermes formosanus Shiraki). The feeding response of termites varied markedly according to the numbers of carbon in alkyl chain.In particular, 1-decyl gallate exhibited the highest feeding deterrence, whereas 1-octadecyl gallate exhibited the highest feeding-stimulating activity.

Enzyme-catalyzed hydrolysis of 1-(4-phenoxyphenoxy)-2-propyl acetate ( 1a ) was examined in a two-liquid phase reaction system of water and the insoluble substrate for the preparation of an enantiomerically pure juvenile hormone analogue (JHA). Almost all the lipases and the microorganisms tested hydrolyzed (R)- 1a preferentially to afford (R)-1-(4-phenoxyphenoxy)-2-propanol (R)- 2a . Pseudomonas cepacia lipase (PCL) showed the greatest enantioselectivity (E > 1,000) and the highest activity. Reaction performance by PCL was studied in some detail from the viewpoints of practical applications. A comparative study was also done of the hydrolysis of 2-(4-phenoxyphenoxy)-1-propyl acetate 1b . A few enzymes including PCL that exhibited great performances for 1a yielded (S)-alcohol and unhydrolyzed (R)-acetate with lower enantioselectivity and higher reaction rates. It was suggested that these results should be discussed from mechanistic standpoints of enzyme action and that steady-state kinetic studies on PCL-catalyzed hydrolysis of enantiomeric substrates might contribute to elucidate the enzyme specificity. An efficient biochemical process was described for the total conversion of 2a to (S)- 2a for the preparation of the physiologically active form of the JHA (S)-pyriproxyfen. The process developed by a combination of lipase-catalyzed hydrolysis and chemical transformation was applicable to various secondary alcohols having a chiral center in the molecule once a highly enantioselective enzyme was found for the target alcohol.

Steady-state kinetics of Pseudomonas cepacia lipase-catalysed hydrolysis of five analogous chiral and achiral substrates, i.e. (R)- and (S)-1-methyl-2-(4-phenoxyphenoxy)ethyl acetates (R)- and (S)-1a, (R)- and (S)-2-methyl-2-(4-phenoxyphenoxy)ethyl acetates (R)- and (S)-1b and 2-(4-phenoxyphenoxy)ethyl acetate 1c, were investigated in sufficiently emulsified reaction mixtures of water-insoluble substrates. The apparent Michaelis constant Km values were identical for all the esters, and no nonproductive binding was observed in these substrates. The apparent catalytic constants kcat were found to reflect the leaving abilities of the alcoholate ions for the fast-reacting enantiomers. These observations, based on the findings that acyl-enzyme intermediate formation was rate-determining in the overall reaction, strongly suggested that all the substrates are bound to the enzyme in the same manner whether or not the alcohol moiety has a medium-sized substituent LM at the stereocentre and that the breakdown of a tetrahedral intermediate is rate-determining in the acylation of the enzyme. Time courses were also studied for the hydrolysis of racemic 1-ethyl-2-(4-phenoxyphenoxy)ethyl acetate 1d together with 1a, 1b and 1c. The enzyme distinguished (R)-1d from its antipode perfectly and hydrolysed only the (R)-enantiomer. These results were interpreted to indicate that LM of the slow-reacting enantiomer is positioned close to the imidazole ring of the catalytic His and hinders NIµ2 of the residue from forming a weak interaction with O1 of the leaving alcohol and that the breakdown of the tetrahedral intermediate is thus inhibited.

Several 2-alkoxycarbonyltrifluoromethanesulfonanilides were prepared to examine their miticidal activity. 4-Halo-2-alkoxycarbonyltrifluoromethanesulfonanilides in particular showed good miticidal activity against Tyrophagus putrescentiae (Tp), Dermatophagoides farinae (Dp) and Chelacaropsis moorei (Cm). Amidoflumet (methyl 5-chloro-2-[(trifluoromethyl)sulfonyl]aminobenzoate) was selected and has been developed as a new miticide for house dust mites.

The insecticidal activity of several new fluorinated pyrethroids was measured using houseflies untreated and treated with piperonyl butoxide (PB). 10, 10-Difluorophenothrin and 10, 10-difluoroallethrin, which include fluorine atoms at a position most easily attacked by mixed function oxidases (mfo) in the acid moiety, showed smaller topical LD50 values on the PB-untreated flies than the parent insecticides but rather large values on the PB-treated flies, suggesting that the introduction of fluorine prevents metabolic oxidation, although it has a negative effect on the interaction with a target site. Monofluorinated analogues of phenothrin, in which the structure of chrysanthemic acid was rearranged, still had moderate insecticidal activity, but flies were scarcely killed by 7 fluoroallethrin into which fluorine was introduced at a position most easily oxidized by mfo in the alcohol moiety. Competitive oxidation of the fluorinated derivatives and the parent compounds showed that fluorine at both the 10- and 7′-positions stabilizes the alkenyl side-chains of the pyrethroids against selenium dioxide and m-chloroperoxybenzoic acid. Photochemical studies with 10, 10-difluorophenothrin indicated that the photo-instability of the cyclopropanecarboxylic part could not be improved by this modification.

Steady-state kinetics of Pseudomonas cepacia lipase-catalysed hydrolysis of five analogous chiral and achiral substrates, i.e. (R)- and (S)-1-methyl-2-(4-phenoxyphenoxy)ethyl acetates (R)- and (S)-1a, (R)- and (S)-2-methyl-2-(4-phenoxyphenoxy)ethyl acetates (R)- and (S)-1b and 2-(4-phenoxyphenoxy)ethyl acetate 1c, were investigated in sufficiently emulsified reaction mixtures of water-insoluble substrates. The apparent Michaelis constant Km values were identical for all the esters, and no nonproductive binding was observed in these substrates. The apparent catalytic constants kcat were found to reflect the leaving abilities of the alcoholate ions for the fast-reacting enantiomers. These observations, based on the findings that acyl-enzyme intermediate formation was rate-determining in the overall reaction, strongly suggested that all the substrates are bound to the enzyme in the same manner whether or not the alcohol moiety has a medium-sized substituent LM at the stereocentre and that the breakdown of a tetrahedral intermediate is rate-determining in the acylation of the enzyme. Time courses were also studied for the hydrolysis of racemic 1-ethyl-2-(4-phenoxyphenoxy)ethyl acetate 1d together with 1a, 1b and 1c. The enzyme distinguished (R)-1d from its antipode perfectly and hydrolysed only the (R)-enantiomer. These results were interpreted to indicate that LM of the slow-reacting enantiomer is positioned close to the imidazole ring of the catalytic His and hinders NIµ2 of the residue from forming a weak interaction with O1 of the leaving alcohol and that the breakdown of the tetrahedral intermediate is thus inhibited.

It is well recognized that the ratio of fluorine-containing pesticides is increasing along with the progress of fluorine chemistry. In recent years, one third of new pesticides are containing fluorine atom (s). In many cases, they have remarkable pesticidal activity as well as physicochemical properties by introduction of fluorine atom (s). We describe the discovery stories of three examples in our laboratory, i.e. amidoflumet, a new trifluoromethanesulfonanilide with high miticidal activity against various house dust mites, Metofluthrin, a potent new fluorinated pyrethroid with extremely high knockdown activity against various mosquitoes, and a new α-pyrone compound, 3- [1R-trans- (2-trifluoromethyl) cyclopropane carbonyl] -4-hydroxy-6-methyl-2-pyrone with outstanding insecticidal activity against Blattella germanica.

A new compound named eucamalol and 4-isopropylbenzyl alcohol were isolated as mosquito repellents from the essential oil of Eucalyptus camaldulensis. The structure of eucamalol was elucidated to be 3-formyl-6α-isopropyl-2-cyclohexen-1β-ol by 1 H NMR analysis and confirmed by synthesis. Both compounds exhibited potent repellent activities against Aedes aegypti

Metofluthrin (SumiOne®, Eminence®) is an exciting novel pyrethroid discovered by Sumitomo Chemical Co., Ltd. It was registered in Japan in January 2005 and is under worldwide development for environmental health use. Metofluthrin has extremely high knockdown activity against various insect pests, especially mosquitoes, as well as high volatility and low mammalian toxicity. This is applicable to not only existing mosquito-controlling devices such as mosquito mats and coils, but also various new formulations and devices such as paper emanators, fan-driven devices, and resin formulations. Metofluthrin is more than 40 times as active as d-allethrin against southern house mosquitoes when used in mosquito coils. This paper describes the story behind the discovery of Metofluthrin and its efficacy against mosquitoes in various formulations.

A new natural mosquito repellent was isolated from fresh leaves of Vitex rotundifolia. Its structure was elucidated by an extensive NMR spectral analysis to be a cyclopentene dialdehyde named rotundial. This compound possessed potent repelling activity against Aedes aegypti.

(1993). The First Practical Synthesis of (S)-Pyrethrolone, an Alcohol Moiety of Natural Pyrethrins I and II. Bioscience, Biotechnology, and Biochemistry: Vol. 57, No. 4, pp. 693-694.