Elm bark beetle

Review Problem 13 This odd looking molecule (TM 169) is closely related to multistriatin, a phenomone of the elm bark beetle, the insect which spreads Dutch ehn disease. How would you synthesise a sample for testing on the beetle ... 

The third component of the elm bark beetle pheromone (p T 4) is a-cubebene (34) which the beetle takes from the tree. Simple disconnections lead to ketone (35). What disconnection would you suggest next ... 

In another approach, the alcohol moiety, formed by an enzymatic hydrolysis of an ester, can act as a nucleophile. In their synthesis of pityol (8-37a), a pheromone of the elm bark beetle, Faber and coworkers [17] used an enzyme-triggered reaction of the diastereomeric mixture of ( )-epoxy ester 8-35 employing an immobilized enzyme preparation (Novo SP 409) or whole lyophilized cells of Rhodococcus erythro-polis NCIMB 11540 (Scheme 8.9). As an intermediate, the enantiopure alcohol 8-36 is formed via kinetic resolution as a mixture ofdiastereomers, which leads to the diastereomeric THF derivatives pityol (8-37a) and 8-37b as a separable mixture with a... 

Claisen rearrangement of glycolates. Two laboratories 2 have reported that allylic glycolate esters undergo Claisen-Ireland rearrangement (6, 276-277) with useful diastereoselectivity. This rearrangement was used in a synthesis of 1, the aggregation pheromone of the European elm bark beetle.1... 

Sn2 Reactions with epoxides and aziridines are also synthetically useful. An example of epoxide cleavage with an organocopper reagent with sp carbon moieties is the enantioselective synthesis of (3S, 4S)-4-methyl-3-heptanol (53), an elm bark beetle (Scolytus multistriatus) pheromone [42]. The chiral epoxy oxazolidine 51 [43], prepared from (R)-phenylglycinol, reacted with a propylmagnesium bromide-derived cuprate at —70 °C to afford the oxazolidine 52 in 74% yield (Scheme 9.12). Compound 52 was converted into the target molecular 53 by conventional procedures. 

The U.S. Forest Service scientists in New York have isolated and identified chemical sex attractants used by elm bark beetles that are responsible for transmitting the fungus causing Dutch elm disease. Examples of attractants are 2,4-dimethyl-5-ethyl-6,8-dioxabicyclo [3.2.1] octane (called multistriatin) and 4-methyl-3-heptanol. In field trials an artificially produced mixture of the compounds has proved attractive to the elm bark beetle. 

Often related insect species are not all sensitive to a particular allomone. For example, juglone is a feeding deterrent to the smaller European elm bark beetle (Scolytus multistriatus) but not to the closely related hickory bark beetle (Scolytus quadrispinosus) (106,107). 

Stereoselective reactions with aldehydes. The related (E)-2-pentenyltin reagent 2 also reacts with aldehydes to form predominantly erythro adducts such as 3. This reaction was used for a stereoselective synthesis of an aggregation pheromone (4) of the European elm bark beetle.1... 

Multistriatin 1 is a pheromone of the elm bark beetle. This beetle distributes the fungus responsible for Dutch elm disease and it was hoped that synthetic multistriatin might trap the beetle and prevent the spread of the disease. It is a cyclic compound with two oxygen atoms both joined to the same carbon atom (C-6 in 1) and we call such ethers acetals. 

The elm bark beetle pheromone contains three compounds multistriatin, the alcohol 12 and a-cubebene 13. At first we shall consider simple molecules like 12 but by the end of the book we shall have thought about molecules at least as complex as multistriatin and cubebene. 

This is the first of four General Strategy chapters in which we discuss important points that apply to the whole of synthetic design rather than one particular area. This chapter concerns general principles to help you choose one C-C disconnection rather than another. Even a simple molecule like the alcohol 1, introduced in chapter 1 as a component of the elm bark beetle pheromone, can be disconnected at any of the five marked bonds. 

We promised in chapter 1 that a synthesis of the elm bark beetle would appear and here it is. It has four chiral centres but one of them (marked as a hidden carbonyl group) is unimportant. Disconnecting the acetal reveals keto-diol 33. If we make 33 it must cyclise to 3—-no other stereochemistry is possible. Further C-C disconnection with alkylation of an enolate in mind reveals symmetrical ketone 34 and a diol 35 with a leaving group (X) at one end and the two chiral centres (marked with circles) adjacent. 

B) Western balsam bark beetle, Dryocoetes confusus formation of endo-brevicomin [(1 F ,5S,7S)-7-ethyl-5-methyl-6,8-dioxabicyclo[3.2.1 ]octane] from ( )-6-nonen-2-one (Vanderwel et a/., 1992a) (C) Spruce beetle, Dendroctonus rufipennis formation of frontalin [(1S, 5fl)-(-)-1,5-dimethyl-6,8-dioxabicyclo[3.2.1]octane] from 6-methyl-6-hepten-2-one (Perez ef a/., 1996 Francke etai, 1995 Francke and Schulz, 1999) (D) European elm bark beetle, Scolytus multistriatus hypothetical formation of oc-multistriatin [(1 S,2F ,4S,5F )-(-)-2,4-dimethyl-5-ethyl-6,8-dioxabicyclo[3.2.1]octane] from 4,6-dimethyl-7-octen-3-one (Francke and Schulz, 1999) and E The colored... 

Birch M. C., Paine T. D. and Miller J. C. (1981) Effectiveness of pheromone masstrapping of the smaller European elm bark beetle. California Agriculture 35, 6-7. 

Blight M. M., Wadhams L. J. and Wenham M. J. (1979a) Chemically-mediated behavior in the large elm bark beetle, Scolytus scolytus. Bull. Entomol. Soc. Am. 25, 122-124. 

Gore W. E., Pearce G. T., Lanier G. N., Simeone J. B., Silverstein R. M., Peacock J. W. and Cuthbert R.A. (1977) Aggregation attractant of the European elm bark beetle, Scolytus multistriatus, production of individual components and related aggregation behavior. J. Chem. Ecol. 3, 429 446. 

Mori K. (1974) Synthesis of (15 2R 45 55)-(-)-a-multistnatin the pheromone in the smaller European elm bark beetle, Scolytus multistriatus. Tetrahedron 32, 1979-1981. 

S, 4S)-4-Methylheptan-3-ol is a component of the aggregation pheromone of the elm bark beetle Scolytus multistriatus. It is readily synthesized from the (s) pinanediol ester of propylboronic acid as shown in Figure B6.2. 

The terpenoid-exocrine theme emphasized by scolytid beetles was again evident when the chemical constitution of the secondary attractant for the smaller European elm bark beetle, Scolytus multistriatus, was elucidated. The aggregation pheromone was identified as a mixture of (-)-4-methyl-3-heptanol, 2,4-dimethyl-5-ethyl-6,8-dioxabicyclo [3.2.1]octane (multistriatin) (XXII), and (-)-a-cubebene (XXIII), a host-derived synergist (70). All three compounds are required for the maximum attraction of beetles. The inactive diastereomers of 4-methyl-3-heptanol and multistriatin did not inhibit the responses of airborne beetles. 

Such a sequence has been successfully used115 for the synthesis of 4-methyl-3-heptanol, the major constituent of the aggregation pheromone of the elm bark beetle (Scolytus multistriatus Marsham)117 and zir-butyM-methyltetrahydro-2-furanone118 known as quercus lactone or oak lactone. ... 

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