5-Multistriatin, synthesis

Application of the preceding strategy to multistriatin synthesis (Scheme 11.26) started with compound 7, which was deoxygenated at C3 and further elaborated to ketone 106 [49]. Wittig methylenation provided 107, and subsequent double bond reduction using Wilkinson s catalyst afforded the dimethylated compound 34 [93]. Further manipulation yielded a-multistriatin 108, the pheromone of Scolytus multistriatus. Other syntheses of this pheromon from sugars have been reported [48,94,95]. 

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 ... 

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... 

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). 

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. 

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. 

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. 

The use of iodoetherification has been exploited in the synthesis of precursors to mono- and bis-THF acetogenins,234 potent antitumor and pesticides. Also, has been used in the synthesis of tetrahydrofuran analogs of precursors to pseudomonic acid.235 As well, N1S has been used as the iodine source, for example in the synthesis of other acetogenins.236 Other compounds synthesized via iodocyclization include ( )-(a)-multistriatin,237 ( )-velbanamine, and ( )-isovalbanamine,238 and (+)-citreoviral.239... 

Stereoselective hydrogenation. A stereoselective synthesis has been reported of the naturally occurring form of a -multistriatin (5), the aggregation pheromone of the European elm beetle, the vector of Dutch elm disease in North America. The synthesis is another example of the value of carbohydrates as chiral precursors to natural products. In this case, the known epoxide 1, derived from D-glucose, was converted in several steps into 2. The crucial next step required hydrogenation to 3 with the 1,3-diaxial configuration of the two methyl groups. The desired selectivity was attained by use of Wilkinson s catalyst. 

As illustrated in Scheme 11.10, enone 32, prepared from D-glucal in a multistep sequence, was reacted with lithium dimethylcuprate. Clean axial attack of the reagent at C4 gave the substituted ketone 33. Subsequent Wittig methylation and reduction was used to introduce the second methyl group of 34, a key intermediate in the synthesis of a-multistriatin. The same sequence was used in the preparation of calcimycin (A23187), the 4-C-methyl synthon 33 being used to construct the two required chirons [50]. 

A number of related enol ethers are accepted as substrates by antibody 14D9. For example, enol ether 57 give (S)-ketone 58, which has been used for a stereospecific synthesis of the pheromone (-)-a-multistriatin (Scheme 19) [87]. 

The synthesis of multistriatin Metallated hydrazones Lithium Enolates and Silyl Enol Ethers... 

Dutch elm disease is a fungal disease, carried by elm bark beetles, which devastated the elm populations of many parts of the world in the 1970s. The beetles assemble at a suitable elm tree on the call of a pheromone containing, among compounds derived from the tree, one charactacteristic of the beetle itself, multistriatin 48. The stereochemistry of this compound was deduced by the synthesis of the various possible isomers as so little natural product was available.8 We shall use three of these syntheses to illustrate the application of aza-enolates to alkylation reactions. 

This time the lithium enolate 68 of 53 was used to give, after equilibration of the centre next to the ketone, a stereoselective synthesis of racemic multistriatin.11 The yield in the final step was 98% of an 85 15 mixture of 48 and 70 separated by chromatography. 

So what exactly is wrong with allyl Grignard reagents Even if they are symmetrical 2, yields tend to be low as the allyl metal bond cleaves easily to give relatively stable allyl radicals that may dimerise or polymerise. When the allyl group is unsymmetrical 9 reaction often occurs at the wrong end of the allyl system, here to give the acid 10 and eventually the tosylate 11 needed in chapter 10 for the synthesis of multistriatin. 

Homogeneous catalysts also proved useful in stereoselective hydrogenation. A crucial step in the total synthesis of the aggregation pheromone a-multistriatin requires hydrogenation to 29 with the 1,3-diaxial configuration of the 2-methyl groups. Selectivity is obtained over RhCl(PPh3)3 ... 

A stereoselective synthesis of optically highly pure enantiomers of -multistriatin (24b) has been developed by Mori and Iwasawa (1980). When using d-( — )-tartaric acid as a starting material, the synthesis route shown in Scheme 1.32 yielded (15, 25, 45, 5/ )-(-)-5-multistriatin, while its antipode, (IR, 2R, 4R, 5S)-( + )-S-multistriatin was formed from l-(-t-)-tartaric acid. 

The synthesis of multistriatin just described has one great fault no attempt was made to control the stereochemistry at the four chiral centres ( in 14) and a mixture of stereoisomers was the result. Only the natural isomer (14) attracts the beetle and a stereoselective synthesis of multistriatin has now been devised (see Chapter 12). We must therefore add stereochemistry to the list of essential background knowledge an organic chemist must have to design syntheses effectively. The list is now ... 

We have already met one important acetal in multistriatin, the insect pheromone discussed in Chapter 1. Another is green leaf lilac perfume (3). The acetal group is easily recognised and the synthesis straightforward. 

The elm bark beetle pheromone multistriatin (3) is a more complicated example. You may remember from Chapter 1 that a single stereoisomer alone attracts the beetle. Making one diastereoisomer by a stereoselective synthesis is not enough. The compound must be a single enantiomer, that is it must be optically active, too. In this chapter we shall consider the question of achieving the correct relative stereochemistry at several chiral centres (such as the four in multistriatin, marked ) and first, the question of making optically active compounds. 

In Chapter 1 we discussed the synthesis of multistriatin (20), a pheromone of the elm bark beetle. The time has come for a stereochemical analysis of this problem. The molecule has four chiral centres ( in 20). One of them (a) turns out to be unimportant as disconnection of the acetal reveals (21) as the true-target. If (21) cyclises to form an acetal it must give (20)—no other stereochemistry is possible. 

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