Multistriatins

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 ... 

Two syntheses of multistriatin follow. For these and for the synthesis in the main text (p T 3) draw diagrams like those above to show which parts of multi-striatin came from which starting materials in each synthesis. Do not be too concerned about the details of each step in the syntheses. 

Exampls Steps in the synthesis of multistriatin givon on page T 3 correspond to disconnections or FGls as follows -... 

T vohlem Does the synthesis of multistriatin on page T3 follow these guidelines ... 

Some insect pheromones are internal ketals. We have already mentioned multistriatin (pp T 2 and 99) and frontalin p 193). Brevicomin (22) is another example. Disconnection of the ketal gives (23) containing a 1,2-diol. Among other syntheses, hydroxy-lation of protected enone (24) by epoxidation and acid catalysed rearrangement gives brevicomin stereo-specifically,... 

Intermolecular addition of radicals, generated by photo-electrochemical catalysis, to activated alkenes can also be brought about. The reaction of 66 is used as a key step in one synthesis of the insect pheromone, brevicomin [219]. The reaction of a secondary radical from 67 occurs at low cathode potentials and without photochemical assistance [219]. This illustrates the equiibrium between a secondary al-kylcobalt(m) species and the radical - cobalt(ii) pair. The carbon radical is eventually captured by reaction with the alkene. Further steps in the synthesis lead to four isomers of the pheromone, multistriatin, each of which is a pure enantiomer since... 

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. 

D. E. Plaumann, B. J. Fitzsimmons, B. M. Richie, and B. Fraser-Reid, Synthetic route to 6,8-dioxabicyclo[3.2.1]octyl pheromones from D-glucose derivatives. 4. Synthesis of (—)-multistriatin, J. Org. Chem. 47 941 (1982). 

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 synthesis of multistriatin just described has one great fault no attempt was made to control the stereochemistry at the four chiral centres (black blobs in 11). Only the natural stereoisomer attracts the beetle and stereoselective syntheses of multistriatin have now been developed. 

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. 

But it is important that multistriatin be made in enantiomerically pure form as well as one diastereomer. Looking back over the synthesis, the first chiral intermediate is 42 and, after some failures, reaction with the isocyanate (+)-(/ )-46 gave a mixture of the urethanes 47 that could be separated by crystallisation. Removal of the urethane by reduction with LiAlH4 gave enantiomerically pure alcohol 42 from which enantiomerically pure (>99%) multistriatin 3 could be made by the methods above. 

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... 

Blight M. M., Wadhams L. J. and Wenham M. J. (1978) Volatiles associated with unmated Scolytus scolytus beetles on English elm differential production of a-multistriatin and 4-methyl-3-heptanol, and their activities in a laboratory bioassay. Insect Biochem. 8, 135-142. 

Elliot W. J., Hromnak G., Fried J. and Lanier G. N. (1979) Synthesis of multistriatin enantiomers and their actions on Scolytus multistriatus (Coleoptera Scolytidae). J. Chem. Ecol. 5, 279-287. 

Gerken B., Grtine S., Vite J. P. and Mori K. (1978) Response of European populations of Scolytus multistriatus to isomers of multistriatin. Naturwissenschaften 65, 110-111. 

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