Brevicomins

The syntheses of brevicomin (67)[109,110] and frontalin[l 11] have been achieved as an elegant application of the intramolecular acetal formation with the diol 66 in dry DME. Optically active frontalin (68) has been synthesized by this cyclization in triglymejl 12]. 

The 3.8-nonadienoate 91, obtained by dimerization-carbonylation, has been converted into several natural products. The synthesis of brevicomin is described in Chapter 3, Section 2.3. Another royal jelly acid [2-decenedioic acid (149)] was prepared by cobalt carbonyl-catalyzed carbonylation of the terminal double bond, followed by isomerization of the double bond to the conjugated position to afford 149[122], Hexadecane-2,15-dione (150) can be prepared by Pd-catalyzed oxidation of the terminal double bond, hydrogenation of the internal double bond, and coupling by Kolbe electrolysis. Aldol condensation mediated by an organoaluminum reagent gave the unsaturated cyclic ketone 151 in 65% yield. Finally, the reduction of 151 afforded muscone (152)[123]. n-Octanol is produced commercially as described beforc[32]. 

It is interesting to speculate that asymmetric induction may be the consequence of the exo anomeric effect, a stereoelectronic effect that favors the conformation 5 that places the aglycone O-C bond antiperiplanar to the pyran C(1) —C(2) bond7fi. Related asymmetric induction has also been observed in aldehyde addition reactions of the related, but racemic, pinacol (Z)-y-(tetrahydropyranyloxy)allylboronate49. As indicated in the examples above, however, the level of diastereoselectivity is modest and the only application in asymmetric synthesis is Wuts exo-brevicomin synthesis75. 

Figure 10.33 Complementary, backbone-inverting approaches for the asymmetric synthesis of the insect pheromone (-l-)-exo-brevicomin.

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,... 

Their conclusions were that the compound 3. 3,4-dehydro-ero-brevicomin (DB) was capable of inter- and intra-sexual activity (see Chap. 7), but only if present in the (R, / -configuration, while its partner compound 4., 2-sec-butyldihydrothiazole (BT), was probably racemised in situ. The DB signal is required in a correct stereochemical form but the thiazolines activity in urine is not affected by a particular chirality (Novotny et al., 1995). 

Another elegant use of nonadienoate is the synthesis of a pheromone called brevicomin (148) (132). The ester was converted to 1,6-nonadiene (149). The terminal double bond was selectively converted to glycol via epoxide. The oxidation with PdCI2 produced brevicomin directly by intramolecular oxidative acetal formation. 

Naturally occurring chiral compounds provide an enormous range and diversity of possible starting materials. To be useful in asymmetric synthesis, they should be readily available in high enantiomeric purity. For many applications, the availability of both enantiomers is desirable. Many chiral molecules can be synthesized from natural carbohydrates or amino acids. The syntheses of (+)-exo-brevicomin (66) and negamycin (67) illustrate the application of such naturally occurring materials. 

Dioxalicyclo[3.2.1]octane, or (+)-exo-brevicomin (66), is the aggregating pheromone of the western pine beetle. It has been prepared from glucose using a procedure based on the retro synthesis design shown in Figure 1-2884 ... 

Use of automated headspace SPDE/GC-MS not only enabled the identification in female African elephant urine of a number of known insect pheromones (compounds 2-6, Fig. 2.1), but also revealed the presence of the beetle biochemical precursors to frontalin (2), exo-brevicomin (3) and ent/o-brevicomin (4), thus suggesting a common biosynthetic pathway (Goodwin et al. 2006). Extensive behavioral bioassays must be performed to determine whether any of these compounds is functioning as a pheromone among African elephants. 

Catalytic olefin metathesis, in only a few years, has risen to be one of the most important and reliable processes in organic synthesis. Recently, several reports by Schrock and Hoveydallsbbond forming transformations efficiently and enan-tioselectively. A recent concise and enantioselective synthesis of exo-brevicomin by Burke utilizes chiral catalyst 91 (Scheme 13) to effect the desymmetriza-tion of 90 through a ring-closing metathesis.11531... 

Scheme 13. Asymmetric Mo-catalyzed ring-closing metathesis used by Burke in a concise total synthesis of exo-brevicomin (1999).

This Payne rearrangement of an optically active epoxide (4) was used for a synthesis of pure (+ )-exo-brevicomin (6) in 31% overall yield. 

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