Japonilure

Enantiomerically pure japonilure [(4JR,5Z)-5-tetradecen-4-olide, 26] is commercially important to attract the Japanese beetle (Popillia japonica), because only pure (4.R,5Z)-26 is bioactive, while ( )-26 is totally inactive. Synthesis of (4 ,5Z)-26 via enzymatic resolution of racemic intermediates was first reported by Sugai [63], and then further studied by Fukusaki [64] to establish the process as summarized in Scheme 39. Lipase PS (Amano) from Pseudomonas sp. and lipase OF (Meito) from Candida cylindracea were shown to be the enzymes of choice. 

Macrolide aggregation pheromones produced by male cucujid beetles are derived from fatty acids. Feeding experiments with labeled oleic, linoleic, and palmitic acids indicate incorporation into the macrolide pheromone component [ 117 ]. The biosynthesis of another group of beetle pheromones, the lactones, involves fatty acid biosynthetic pathways. Japonilure and buibuilactone biosynthesized by the female scarab, Anomalajaponica, involves A9 desaturation of 16 and 18 carbon fatty acids to produce Z9-16 CoA and Z9-18 CoA,hydroxylation at carbon 8 followed by two rounds of limited chain shortening and cyclization to the lactone [118]. The hydroxylation step appears to be stereospecific [118]. 

Fig. 10 TLC plate showing degradation of (R)- and (S)-japonilure (upper spots) by esterases from the legs (Leg) and antennae (Ant) of the Japanese beetle. The corresponding hydroxy-acids appear as lower bands. Note the slower degradation of the behavioral antagonist, (S)-japonilure, by sensillar esterase(s) from the antennae. Neither (R)- nor (S)-japonilure is degraded in control experiments (data not shown) under the same conditions, i.e., with the compounds incubated in buffer without Japanese beetle tissue extracts...

Females of several species use (R)-5-[(lZ)-l-octenyl]oxacyclopentan-2-one, buibuilactone 69 [ 140-144]. The first y-lactone identified from a scarab beetle was (R)-5-[(Z)-l-decenyl]oxacyclopentan-2-one, japonilure 70, the female produced sex pheromone of the Japanese beetle Popillia japonica [145]. Both 69 and 70 are components of specific blends of several species [140-143]. The Japanese beetle is extremely sensitive to the non-natural enantiomer of his pheromone as little as 1% of the (S)-enantiomer inhibits the attractiveness of the pheromone [ 145]. With respect to species discrimination, this is particularly... 

Several syntheses of optically active japonilure and related lactones involve enzyme-catalysed transformations [153] however, recently, it has been efficiently prepared in high enantiomeric purity via boronic esters of 1,2-dicyclo-hexyl-l,2-ethanediol [154] (Fig. 5). 

The boronic acid ester B was synthesized by transesterification of the corresponding pinacolester A with (lR,2R)-l,2-dicyclohexyl-l,2-dihydroxyethane. Stereoselective chlorination of B was carried out with (dichloromethyl) lithium and zinc chloride. Reaction of the obtained chloroboronic ester C with lithio 1-decyne followed by oxidation of the intermediate D with alkaline hydrogen peroxide afforded the propargylic alcohol E. Treatment with acid to saponify the tert-butyl ester moiety and to achieve ring closure, produced lactone F. Finally, Lindlar-hydrogenation provided japonilure 70 in an excellent yield and high enantiomeric purity. 

Japonilure R), the sex pheromone of the female Japanese beetle. Papilla japonica and its enantiomer, (5)-(+)-(5Z )-tetradecen-4-olide, which is the pheromone of the Osaka beetle, Anomala osakana have been synthesized using a highly convergent procedure and in satisfactory overall yields. 

Figure 6.4 Lactone pheromone components produced by beetles in the genus Anomala (family Scarabaeidae) (R)- and (S)-(R,Z)-5-(-)-(dec-1-enyl)-oxacyclopentan-2-one (japonilure) and (fl,Z)-5-(-)-(oct-1-enyl)-oxacyclopentan-2-one (buibuilactone). Species known to use the compounds as pheromone components are indicated (reviewed in Leal, 1999).

It is not only drugs that have to be manufactured enantiomerically pure. This simple lactone is the pheromone released by Japanese beetles (Popilia japonica) as a means of communication. The beetles, whose larvae are serious crop pests, are attracted by the pheromone, and synthetic pheromone is marketed as Japonilure to bait beetle traps. Provided the synthetic pheromone is the stereoisomer shown, with the Zdouble bond and the R configuration at the stereogenic centre, only 25 jug per trap catches thousands of beetles. You first met this compound in Chapter 32, where we pointed out that double bond stereocontrol was important since the -isomer of the pheromone is virtually useless as a bait (it retains only about 10% of the activity). Even more important is control over the configuration at the chiral centre, because the S-enantiomer of the pheromone is not only inactive in attracting the beetles, but acts as a powerful inhibitor of the R-enantiomer—even 1% S-enantiomer in a sample of pheromone destroys the activity. 

R,5Z)-Japonilure r Mrt iKj. jl k Japanese beetle FopWia Japonica) S Enzymatic resolution (Lipase PS) of racemates [169] [170]... 

Figure 4.32 Synthesis of (R)-japonilure by Tumlinson et al. Modified by permission of Shokabo Publishing Co., Ltd...

Tumlinson and coworkers synthesized (R)-japonilure (87) by the Wittig reaction between A and B as shown in Figure 4.32.60 The aldehyde A was prepared from D-glutamic acid. In the course of the Wittig... 

Response of the gypsy moth to the enantiomers of disparlure (85) showed that (7R,8S)-85 was bioactive, while (7S,8R)-85 was inhibitory. The very strong inhibitory action of the opposite (5 )-isomer of japonilure (R)-87 is remarkable. In practical application of these pheromones, their pure enantiomers have to be manufactured. 

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