Spiroacetal pheromones

This process has found occasional use in the synthesis of heterocycles. The major product resulting from the reaction of MeLi on the dibromocarbene adduct (51) is the tetrahydrofuran (52), as shown in equation (105).189 In a novel approach to the synthesis of spiroacetal pheromones, caibene insertion into an acetal C—H bond was studied (equation 106).252 Unfortunately, the reaction proceeds in low yield and the approach is further hampered by the lack of stereocontrol in the ring opening of the cyclopropane. Carbene insertions into N—H and C—H bonds adjacent to nitrogen have been shown to give azabicyclo systems, as shown in equations (107) and (108).188... 

Insertion of a carbenoid into a C-H bond has also been performed under synthetic conditions. A recent novel approach to spiroacetal pheromone (equation 123) is unfortunately hampered by the absence of regioselectivity in the ultimate cyclopropane hydrogenation step (see Section III.A). 

Figure 4.35 Synthesis of the spiroacetal pheromone of Andrena wilkella (I). Modified by permission of Shokabo Publishing Co., Ltd...

Out of numerous endo-type multiple ring closure cascades, only the double cyclization of (98) is mentioned here. This leads to the bis(spiroacetal) entity (99 Scheme 48), which is present in polyether antibiotics, insect pheromones and other important natural products. ... 

Bicyclic acetals and spiroacetals based on cryptic ketodiols of polyacetate or, less frequently, polypropanoid origin are widespread in nature. They play important roles as pheromones in intraspecific and interspecific communication in many insect species, and thus their chemistry is discussed in greater detail in Chapter 4.04. 

The authors reported that these spiroacetals had been found in insect pheromones. 

The synthesis of (2 5, 6R, 8 S)-2,8-dimethyl-l,7-dioxaspiro[5,5]undecane (868), one of the spiroacetal components of the pheromone isolated from the olive fruit fly, hinges on a dialkylation of tolylmethyl isocyanide with bromide 866. The bromide is obtained from 845b by sequential reduction of the olefin and ester followed by conversion of the resulting alcohol to bromide. Acidic hydrolysis of dialkylated product 867 provides the pheromone 868 directly... 

Ethyl-2-methyl-l,6-dioxaspiro[4.5]decane is a constituent of the antiaggregative pheromone produced by several varieties of bees. All of the four thermodynamically stable stereoisomers of this spiroacetal have been synthesized using (5)-malic acid and (5)-lactic acid as the sources of chirality [15]. 

Other spiroacetal natural products have been prepared using malic acid-derived epoxides as the chiral source (Scheme 54). Chalcogran (407, R=CH3, = 1) is the principal component of the aggregation pheromone of the beetle Pityogenes chalcographus (L.), a pest of Norway spruce. Spiroacetal 407 (R—H, = 2) is a minor volatile component found in the common wasp, Paravespula vulgaris. 

C,H, 02, Mr 156.22, bp. 73 °C (4.0 kPa) (25,5R)-iso-mer [a] -100° (hexane) (2S,5S)-isomer [a] r%° (hexane). Aggregation pheromone of bark beetles of the genus Pityogenes. Males of P. chalcographm excrete this spiroacetal as a mixture of the (25,55)- and (25,5/()-isomers to attract males and females of the same species to colonize a host tree. Only the (25,5/ )-isomer has an attracting action which is dramatically increased by simultaneously excreted, extremely small amounts of methyl (2E,4Z)-2,4-decadienoate (C, H,g02, Mr 182.26). Isomers of C. are the pheromones conophthorin and olean, the sexual attractant of the olive fruit fly Dacus oleae. C. is currently the economically most important pheromone with a market value in 1995 of ca. 20 Mio. DM for its use against forest pests. 

C9H,g02, Mr 156.22, liquid with a flower-like odor, bp. 77 °C (6.53 kPa). Isolated from the sting apparatus of wasps (Paravespula and Dolichovespula) identified as a spiroacetal. C. is also produced by bark beetles of the genera Conophthoms, Cryphalus, and Leperisinus and used by them as pheromone to deter members of the same species (Alarm pheromone) in order to prevent local overpopulations. In Conophthoms species C. has the (55,7S)-configuration, [a] -78.3° (pentane). C. has also been detected in the bark of pine trees, cork oak, and the odor of orchids see also chtdcograne, oleane. 

Interestingly, even natural products that contain a spiroacetal as the only stereogenic element are known [52]. The parent 6,6-spiroacetal is also a natural product, olean, the major female-produced sex pheromone of the olive fruit fly (Scheme 18) [53]. Although it has been isolated from natural sources as a racemic mixture, it was found that its two mirror enantiomers display a remarkable sex-specific property. The (/ )-enantiomer is active on males and the (S)-enantiomer on females of the olive fruit fly [54]. 

Asymmetric hydrolysis of acetate ( )-46 with a spiroacetal ring system was achieved with pig liver esterase (PLE) to give alcohol (4S,6S)-47 and the xmreacted acetate 4R,6R)-46 (Figure 24.24) [28]. The alcohol (4S,6S)-47 is a component of the sex pheromone of the olive fruit fly. 

Francke et al (632) identiried spiroacetal (627) as an aggregation pheromone in the bark beetle Pityogenes chalcographus. 

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