Insect pheromones 7-lactone

Both chiral lactones and ketones have been utilized in asymmetric synthesis of bioactive compounds like lipoic acid [175[ and natural products like various insect pheromones [176[. 

Ring-opening95 of tetrahydrofuran with TBDMS-Mn(CO)5, generated in situ from TBDMSOTf and NaMn(CO)5, proved a key step (equation 22) in the synthesis of spiroke-tal lactones, precursors of certain insect pheromones. 

An asymmetric reducing agent (49), prepared from LAH, (-)-)V-methylephedrine (14) and 3,5-di-methylphenol in a 1 1 2 ratio, reduces acetophenone with 83.8% A series of aromatic and alkynyl ketones are reduced by (49) to the corresponding (f )-alcohols (Scheme 1)P Some of the products are useful intermediates for the synthesis of 7-lactone insect pheromones. " ... 

The Baeyer-Villiger reaction is regioselective — the more substituted group migrates—and stereospecific — it does so with retention. Hydroxy ketone (22) was needed for insect pheromone synthesis and is a 1,6-difunctionalised compound. It could be made by nucleophilic displacement by an organo-metallic reagent (R ) on lactone (23), the Baeyer-Villiger product from (24) which can be made from aromatic (26). 

In connection with his work on insect pheromones, Silverstein wanted a general synthesis of optically active lactones (8). For a general synthesis, disconnection of R is best and as this also leaves a fragment > having the skeleton of available glutamic add (10), this route wm chosen, A series of trivial disconnections is needed, but this is a price worth paying for a readily available, optically active, starting material. 

Spiroketals.- The discovery that this class of compounds includes insect pheromones has stimulated extensive synthetic effort. A variety of 1,6-dioxaspiro[4.4]nonanesand 1, 6-dioxaspiro[4.5]dec-anes have been prepared by reaction of lithium salts of protected alkynols with equimolar amounts of lactones followed by hydrogena tion and acid-catalysed deprotection and cyclisation (Scheme 16). 

The corresponding homogeneous complexes (104-108) were tested in various processes, including (i) ROMP of COE (ii) CM of 5-decene with 5-hexenyl acetate to produce the insect pheromone 5-decenyl acetate [92] and (iii) the macrocychc RCM of 5-hexen-l-yl-lO-undecenoate to generate the 16-membered ring lactone [86]. The pyridine-alkoxide-modified catalysts were foimd to react more slowly than the commercial catalysts for the ROMP of COE, but displayed good activities for the CM and macrocychc RCM reactions. 

Midland and his co-workers have continued their work on the reduction of acetylenic keto-esters, e.g. (97), with chiral boranes to include a highly efficient synthesis of the insect pheromone (98). Catalytic hydrogenation of the lactone tetra-acetate (99) in the presence of triethylamine gives the triacetate (100) by... 

The synthetic utility of P-lactones is clearly demonstrated by the following two examples (i) enolates of p-lactones react with aldehydes in a three-centre diastereoselective (> 95 %) aldol condensation (Scheme 83) (ii) the copper(i)-catalysed Grignard opening of 3-methylpropiolactone is used in a synthesis of insect pheromones. ... 

The insect pheromone (140) has been prepared in an optically pure form by the chiral reduction of the keto-ester (139), followed by lactonization and partial reduction of the acetylene group (Scheme 85). 

In another example, Oda et al. have utilized an acid-catalyzed lactonization of a 8-hydroxy amide derivative in the synthesis of insect pheromone 12 [43] (Scheme 7). The condensation of the diacid dichloride derived from keto diacid 39, with (/ )-(-p)-[l,l -binaphthyl]-2,2 -diamine, afforded the coupled product 41,... 

Females of the Japanese beetle, Popilla japonica, synthesize one of the few lactonic sex pheromones that have been identified in insects (52). Tumlinson et aK (52) have recently identified the powerful sex pheromone of this insect as (R.ZJ-5-(1-decenyl)dihydro-2(3H)-furanone (X). In addition to the Z-isomer, the -isomer is also present as well as the saturated... 

The scarab beetle Osmodenna eremita and its larval predator, the click beetle Elaterferrugineus, are known as indicators of the species richness of insect fauna of hollow deciduous trees in Northern Europe. (R)-4-Decanolide 13 (Figure 4) is the male-produced sex pheromone of 0. eremita 2 Lactone 13 is also employed by E. ferrugineus as a kairomone for the detection of tree hollows containing the larvae of 0. eremita u... 

Many arthropod pheromones are of putative polyketide origin, which are discussed in greater detail in Chapter 4.04. One noteworthy example is the novel 2,3-disubstituted /3-lactone, vittatalactone (73), recently characterized as a suspected male-produced aggregation pheromone for the striped cucumber beetle, Acalymma vittatum Vittatalactone is the first /3-lactone to be isolated from a beetle, and is only the third such structure to be characterized from an insect (Figure 24). 

Anyone who has owned a female cat or dog knows that sex pheromones are not limited to insects. Female cats or dogs widely advertise, by odor, their sexual availability when they are "in heat." This type of pheromone is not uncommon to mammals. Some persons even believe that hiunan pheromones are responsible for attracting certain sensitive males and females to one another. This idea is, of course, responsible for many of the perfumes now widely available. Whether or not the idea is correct cannot yet be established, but there are proven sexual differences in the ability of humans to smell certain substances. For instance, Exaltolide, a synthetic lactone of 14-hydroxytetradecanoic acid, can be perceived only by females or males after they have been injected with an estrogen. Exaltolide is very similar in overall structure to civetone (civet cat) and muskone (musk deer), which are two naturally occurring compounds believed to be mammalian sex pheromones. 

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