Ipsdienol enantiomers

FIGURE 2 Pheromone structures of the American cockroach (periplanone B), the brownbanded cockroach (supellapyrone), bark beetles (ipsdienol enantiomers), and the cabbage looper moth (six acetates). 

Attempts to investigate boll weevil (Anthonomus grandis) pheromone biosynthesis have identified isomerization, dehydration, and oxidation of the pheromone alcohols, and anticipated allylic oxidation of myrcene and limonene, but no evidence for the cyclization of acyclic precursors. The aggregation pheromones of bark beetles have been reviewed. Ips calligraphus responds to ipsdienol only in the presence of the c/5-verbenol (32) large additional concentrations of the enantiomer (l/ ,4i ,5/ )-(32) reduce beetle response. 5-(-)-Ipsenol, the pheromone of Ips grandicollis, increases the response of /. avulsus to its own pheromone ipsdienol. ... 

The major aggregation pheromone components of T. typographies are e-is-verbenol and 2-methyl-3-buten-ol (1). Cis-verbenol is common to several Ips species (2). Only the Ts)-(-) enantiomer evokes response in field experiments (3). Methylbutenol is specific to I. typographies. A different isomer is part of the pheromone of the related species Ips oembrae, which lives on larch in Europe C4). Ipsdienol (2-methyl-6-methylene-2, 7-octadiene-4-ol), which... 

Brown, H. C., Randad, R. S. B-2 -lsoprenyldiisopinocampheylborane an efficient reagent for the chiral isoprenylation of aldehydes. A convenient route to both enantiomers of ipsenol and ipsdienol. Tetrahedron Lett. 1990, 31,455-458. 

In the case of ipsdienol (112), the stereochemistry-bioactivity relationship is much more complicated and interesting. My first synthesis of (/ )-(—)-ipsdienol (112 ) in 1976 from (fC j-glyccraldchyde allowed the assignment of S-configuration to (+)-ipsdienol isolated by Silverstein.115 Our second synthesis to provide both the enantiomers of ipsdienol employed the enantiomers of malic acid as starting materials.113 That synthesis, however, was lengthy and yielded the final products of 90% ee due to the partial racemization in the course of the synthesis. 

Our third synthesis of the enantiomers of ipsdienol started from the enantiomers of serine as shown in Figure 4.66.116 (A-Serine was converted to epoxide A, which was treated with a Grignard reagent prepared from chloroprene to give hydroxy ester B. Subsequently, B afforded (7 )-ipsdienol (112, >96% ee). Similarly, (R)-serine furnished (S)-112. 

Later biological studies on the enantiomers of ipsdienol revealed the following interesting facts. Ips paraconfusus employs (S )-(+)-112 as the pheromone, while Ips calligraphus and Ips avulsus use (R)-(—)-112. Ipspini in New York employs a mixture of (R)-112 and (S)-112 = 32-56 68-44, while that in California uses a mixture of (R)-112 and (S)-112 = 89-98 11-2. Thus, different enantiomers are employed by different species or subspecies. 

Figure 4.66 Synthesis of the enantiomers of ipsdienol. Modified by permission of Shokabo Publishing Co., Ltd...

Kubo andNakatsu (11) separated the racemic pheromone ipsdienol into pure enantiomers using an indirect approach. ( )-Ipsdienol was derivatized with (+)-a-methoxy-a-(trifluoromethyl)-phenylacetic acid (MTPA) to yield a mixture of diastereoisomers (Fig. 19), which were separated by conventional normal phase preparative HPLC using a nucleosil silica column with product recycling (see Subheading 2.3.4.). After seven cycles the diastereomers were... 

However, a source of the non-natural 9S isomer (2) was first required. The ready availability of natural crinitol made a racemization/resolution route, as illustrated in Scheme 1, attractive. Racemization was accomplished by Collins oxidation (16,25) to the dicarbonyl compound (14), followed by lithium aluminum hydride (LAH) reduction to give the racemic mixture (1 + 2). Resolution via diastereomeric derivatives seemed plausible. Esterification with enantiomerically pure a-methoxy-a-(trifluoromethyl) phenylacetic acid (MTPA) (17), followed by separation of diastereomers by recycle-HPLC (R-HPLC), had earlier been used to purify enantiomers of ipsenol and ipsdienol (26). A model system, the resolution of -3-nonen-2-ol, a secondary allylic alcohol naturally occurring in Rooibos tea (16,27), also worked satisfactorily. Therefore, the route using the bis-(MTPA) esters was selected for crinitol. 

Bark beetles of the genus Ips are pests which attack pine and spruce trees. They use ipsdienols as aggregation pheromones, Ips confusus emitting the (5)-(-l-)-, and Ips paraconfusus the (.K)-(-)-enantiomer The beetles receive the myrcenes (section 2.2) occurring in conifers with their food and metabolize them to ipsdienols some evidence for de-novo synthesis by the bugs is also reported. In order to catch the beetles, pheromone traps are supplied with both enantiomers of ipsdienol which are produced from (-l-)-verbenone, a constituent of the Spanish verbena oil (section 2.4.3). This terpenone, also available by oxidation of a-pinene, is isomerized to the enantiomers of 2(10)-pinen-4-one via three steps (reduction, protonation, oxidation). After separation, both enantiomers are reduced by lithiumaluminumhydride. Pyrolytic cycloreversion of the resulting diastereomeric 2(10)-pinen-4-ols provides the enantiomers of ipsdienol... 

It happens, that some species within a genus utilise the same enantiomer, whereas other species employ the opposite enantiomer. For example, ipsdienol is an important pheromone of spruce bark beetles. Ips calligra-phus and Ips avulsus use (fl)-ipsdienol as their attractant Ips paraconfusus, on the other hand, uses the (S)-enantiomer its (fl)-enantiomer acts even as an inhibitor. [176]... 

The Ipspini at the East Coast of the USA uses (S)-ipsdienol as the pheromone in contrast, the Ipspini at the West Coast uses the (H)-enantiomer. This shows that the very same species has developed two different pheromone receptors for communication. 

Male I. paraconfusus have a greater overall antennal sensitivity to ( - )ipsdie-nol produced by I. pini than to their pheromonal component (+)ipsdienol (Light and Birch, 1982). Females, however, show a greater and more typical response to their pheromonal enantiomer. 

Table 12.2 Mutual interruption of response to their aggregation pheromones by Ips paraconfusus and I. pini. Treatments are male beetles of one or both species boring in ponderosa pine, with, in some treatments, one or more enantiomers or racemic ipsenol and ipsdienol. Responses are given as a percentage of the response to conspecifics. (Data from Birch and Wood, 1975 Light and Birch, 1979 Birch et al., 1980a)...

During the evolution of bark beetles, their hosts and associated fungi, parasites, predators and organisms, the composition of bark beetle pheromones will probably have been modified as other species evolved responses to components of the pheromone and exerted selection pressures on the beetle population. There is only circumstantial evidence that this might have happened. For example, in the experiments on widely separated populations of 7. pini (Lanier et al., 1972), California beetles attracted more local 7. pini than did New York beetles, and vice versa in New York. However, New York beetles in California attracted far more of the local predator E. lecontei than did the local 7. pini. California and New York 7. pini use different ratios of the enantiomers of ipsdienol as their pheromones. The high resolution of (-)ipsdienol in California populations versus the blend in New York supports the idea of coevolution of chemical systems of predator and prey production of and response to (+ )ipsdienol being eliminated in California by a predator which had evolved specific responses to it. Perhaps in the absence of E. lecontei in New York there was no pressure to resolve the blend. 

Ips calligraphus responds to ipsdienol and cw-verbenol (323). (8)-cis-Verbenol (234) is the active enantiomer and the response is not inhibited by (7 )-c -verbenol when present at a 1 1 ratio but is inhibited when the JR-enantiomer is present at a 10-fold higher amount (324). I. typo-graphus also responds to (5)-cw-verbenol (325). The lack of information... 

Birch and coworkers (327) have shown in laboratory bioassays that female Ips pint from the western USA respond well to (—)-ipsdienol (266a, Scheme 52) but do not respond to either the (-l-)-isomer (266b) or a racemic mixture. This contrasts with the eastern I. pini which responds to the (-i-)-isomer and a racemic mixture but does not respond to (-)-ipsdienol (328). The mechanism for the intraspecific variation in pheromone systems of I. pini described by Lanier et al. (329) seems partially resolved. Plummer et al. (45) found that the natural enantiomer composition of ipsdienol for I. pini from Idaho to be 100% (—). The European fir engraver, Pityokteines curvidens, aggregates only in response to the 5 -(-)-isomer of ipsenol, and the i -(-l-)-isomer is inactive (330). 

---