Pheromone epoxides

Bell, T. W. and Ciaccio, J.A. (1988). Alkylative epoxide rearrangement, application to stereoselective synthesis of chiral pheromone epoxides. Tetrahedron Lett., 29, 865-868. 

Functional group transformations of epoxides rank among the fundamental reactions of organic chemistry and epoxides are commonplace natural products The female gypsy moth for example attracts the male by emittmg an epoxide known as disparlure On detechng the presence of this pheromone the male follows the scent to its ongm and mates with the female... 

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,... 

This is the first example of a reaction for which the presence of a chelating ligand was observed to facilitate rather than retard metal-catalysed epoxidation (Gao et al., 1987). It was found that the use of molecular sieves greatly improves this process by removing minute amounts of water present in the reaction medium. Water was found to deactivate the catalyst. All these developments led to an improved catalytic version that allows a five-fold increased substrate concentration relative to the stoichiometric method. Sensitive water-soluble, optically active glycidols can be prepared in an efficient manner by an in situ derivatisation. This epoxidation method appears to be competitive with enzyme-catalysed processes and was applied in 1981 for the commercial production of the gypsy moth pheromone, (-1-) disparlure, used for insect control (Eqn. (25)). 

The substrate-controlled addition of 18 to 19 proceeded with good enantioselec-tivity and was used to prepare the epoxide (+)-dispalure, a gypsy moth pheromone.184... 

R,8S)-(+)-Disparlure (12) is the female sex pheromone of the gypsy moth (Lymantria dispar). Advent of Sharpless asymmetric dihydroxylation (AD) allowed several new syntheses of 12 possible. Sharpless synthesized 12 as shown in Scheme 17 [27]. Scheme 18 summarizes Ko s synthesis of 12 employing AD-mix-a [28]. He extended the carbon chain of A by Payne rearrangement followed by alkylation of an alkynide anion with the resulting epoxide to give B. Keinan developed another AD-based synthesis of 12 as shown in Scheme 19 [29]. Mit-sunobu inversion of A to give B was the key step, and the diol C could be purified by recrystallization. 

A new analytical method [34] for the enantiomeric purity of epoxide pheromones as well as a new method [35] for stereochemical inversion of saturated epoxides were reported by Oliver. 

Posticlure [(6Z,9Z,llS,12S)-ll,12-epoxy-6,9-henicosadiene, 14] is the female sex pheromone of the tussock moth, Orgyia postica. Wakamura s first synthesis of 14 was achieved by employing Sharpless asymmetric epoxidation, and the final product was of 59% ee [38]. Mori prepared 14 of high purity as shown in Scheme 25 basing on asymmetric dihydroxylation (AD) [39]. Kumar also published an AD-based synthesis of 14 [40], which was more lengthy and less efficient than Mori s [39]. 

S,12S)-2,12-Diacetoxytridecane (17) is a component of the female pheromone of pea midges (Contarinia pisi). Kitching synthesized 17 as shown in Scheme 28 by employing Jacobsen s hydrolytic kinetic resolution of terminal epoxides with a (salen)Co(OAc) complex, (S,S)-B [46]. By this reaction bis-... 

Synthesis of Oxygen Heterocycles (Excluding Epoxides, Hemiacetals, Lactones and Acetals) as Pheromones... 

It is now clear that pure pheromones can be synthesized in quantity. The problem is how to prepare them simply and efficiently. New synthetic methodologies are always welcome to improve the existing syntheses. Organoborane reactions and organotransition metal chemistry contributed much to improve the efficiency of carbon-carbon bond formation, while asymmetric epoxidations and dihydroxylations as well as enzymatic reactions greatly improved the enantiomeric purity of synthetic pheromones. 

Biosynthesis of triene pheromone components with a triene double bond system that is n-3 (3,6,9-) are probably produced from linolenic acid [49]. Moths in the families Geometridae, Arctiidae, and Noctuidae apparently utilize linoleic and linolenic acid as precursors for their pheromones that must be obtained in the diet,since moths can not synthesize these fatty acids [50]. Most of the Type II pheromones are produced by chain elongation and decarboxylation to form hydrocarbons [51]. Oxygen is added to one of the double bonds in the polyunsaturated hydrocarbon to produce an epoxide [49]. 

Several families of moths utilize hydrocarbons or epoxides of hydrocarbons as their sex pheromone. Oenocyte cells produce hydrocarbons that are transported through the hemolymph by lipophorin [71]. In a study using arctiid moths it was shown that sex pheromone hydrocarbons are transported on the same lipophorin particle as the hydrocarbons destined for the cuticular surface [ 17]. Therefore, specific uptake of the sex pheromone hydrocarbon occurred in pheromone glands [17]. Similar findings have been found with other moths [72-74]. The mechanism behind this specific uptake of one hydrocarbon from a potential pool of other hydrocarbons is unknown. 

A study using the gypsy moth, Lymantria dispar, illustrates the overall pathways involved in production of epoxide pheromone components (Fig. 3) [77]. This insect uses disparlure, Me2,epo7-18 H, as a pheromone component. In-... 

One of the sex pheromone components of the housefly, Musca domestica, is Z9-21 H that is found on the cuticular surface of the fly. This compound is formed by the elongation of Z9-18 CoA using malonyl-CoA and NADPH to Z15-24 CoA which is decarboxylated to form Z9-21 Hc (Fig. 3) [78-80]. Other pheromone components include an epoxide and ketone that are produced from Z9-21 Hc by a cytochrome P450 [81,82] and methyl-branched alkanes that are produced by the substitution of methylmalonyl-CoA in place of malonyl-CoA at specific points during chain elongation [83,84]. A novel microsomal fatty acid synthase is involved in production of methyl-branched alkanes in most insects [85-87]. This fatty acid synthase is different from the ubiquitous soluble fatty acid synthase that produces saturated straight chain fatty acids in that it is found in the microsomes and prefers methylmalonyl-CoA. The amino acids valine and isoleucine can provide the carbon skeletons for methylmalonyl-CoA as well as propionate [83]. 

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. 

A total synthesis of (35, 4/ )-(+)-eldanolide (246), a sex attractant pheromone, has been reported (243). Compound 246 was synthesized by two different routes, both involving the butenolide 245 as the key precursor. The higher-yielding sequence is described here. Treatment of the tosylate acetal 242 with methanolic sodium methoxide led, as previously described by Hoffman and Ladner (244), to the epoxide 243. Addition of lithium diiso-butenylcuprate to 243 afforded 244, which after successive hydrolysis of the isopropylidene group, treatment with triethyl orthoformate, and pyrolysis,... 

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