Chrysanthemic acids

Comments The diene A is symmetrical so it doesn t matter which double bond is attacked by the carbene. On the other hand, it may be difficult to stop carbene addition to the second double bond. The only control over the stereochemistry will be that the trans compound we want is more stable. Japanese chemists have recently synthesised optically active trans chrysanthemic acid by this route (Tetrahedron Letters. 1977, 2599). 

In all, only six steps are involved, making this a most economical synthesis. Chrysanthemic acid is important enough to have been made in many other ways too (e.g. Tetralredron Letters, 1976, 2441 Bull. Soc. Chim. France, 1966, 3499). 

Chrysanthemic acid (obtained from chrysanthemum flowers)... 

Hydrolysis of cinenn I gives an optically active carboxylic acid (+) chrysanthemic acid Ozonolysis of (+) chrysanthemic acid followed by oxidation gives acetone and an optically active dicarboxyhc acid (—) caronic acid (C7H10O4) What is the struc ture of (—) caronic acid" Are the two carboxyl groups cis or trans to each other What does this information tell you about the structure of (+) chrysanthemic acid" ... 

Pyrethroids from Chiysanthemic Acid. The unsaturated side chains of the aHethrolone alcohol moieties of the natural pyrethrins are readily epoxidized by microsomal oxidases and converted to diols, thus detoxifying the insecticides. Esterification of chrysanthemic acid (9), R = CH3, with substituted ben2yl alcohols produces usehil insecticides barthrin [70-43-9J, 2-chloro-3,4-methylenedioxyben2yl (+)-i7j ,/n7 j -chrysanthemate, and dimethrin [70-38-2] 2,4-dimethylben2yl (+)-i7j ,/n7 j -chrysanthemate. These have alimited spectmm of insecticidal activity but are of very low mammalian toxicity, ie, rat oralLD s >20,000 mg/kg. 

Pyrethroids with Modified Chrysanthemate Esters. Newer pyrethroids incorporate optimized chrysanthemic acid components to retard detoxication by microsomal oxidases and these are esterified with a variety of optimized alcohol moieties therefore increasing persistence. 

Chrysanthemic acid, structure of, 107 Chymotrypsin, peptide cleavage with, 1033... 

The columns labeled PI reflect the total of pyrethrin I and cinerin I just as in the AO AC procedure. The gas chromatographic results are in terms of the total amount of the mixture but were analyzed as the methyl ester of chrysanthemic acid. The present state of the determination of PII (pyrethrin II plus cinerin II) is not complete because of the erratic extractability of the dicarboxylic acids from the hydrolysis mixture. The gas chromatographic pattern is distinct and straightforward. As the extraction procedure for PII is improved, the gas chromatographic method will be more applicable. The present recovery of PII is in the range of 80 to 90%. The average of the values shown in Table II for PI is 98.0%. 

Both cis- and trans-chrysanthemic nitriles and amides were resolved into highly enantiopure amides and acids by Rhodococcus sp. whole cells [85]. The overall enantioselectivity of reactions of nitriles originated from the combined effects of a higher (lJ )-selective amidase and a (IJ )-selective nitrile hydratase (Figure 6.29). Chrysanthemic acids are related to constituents of pyrethrum flowers and insecticides. 

Bicyclic ketone (33) was needed for a chrysanthemic acid synthesis. tarbene disconnection next to the ketone group (Chapter T30) reveals y. (5-unsaturated acid (35) as an intermediate, available by a Claisen-Cope rearrangement. 

For the synthesis of permethric acid esters 16 from l,l-dichloro-4-methyl-l,3-pentadiene and of chrysanthemic acid esters from 2,5-dimethyl-2,4-hexadienes, it seems that the yields are less sensitive to the choice of the catalyst 72 77). It is evident, however, that Rh2(OOCCF3)4 is again less efficient than other rhodium acetates. The influence of the alkyl group of the diazoacetate on the yields is only marginal for the chrysanthemic acid esters, but the yield of permethric acid esters 16 varies in a catalyst-dependent non-predictable way when methyl, ethyl, n-butyl or f-butyl diazoacetate are used77). 

Some care must be taken in drawing conclusions from the E/Z or syn/anti selectivity of a given catalyst/alkene combination. The intrinsic stereoselectivity may be altered in some cases by subsequent isomerizations initiated by the catalyst. For example, epimerization of disubstituted vinylcyclopropanes is effectively catalyzed by palladium compounds the cis - trans rearrangement of ethyl chrysanthemate or of chrysanthemic acid occurs already at room temperature in the presence of PdCl2 L2 (L = MeCN, EtCN, PhCN)96 Oxycyclopropane carboxylic esters undergo metal-... 

The grem-dibromocyclopropanes 152 bearing a hydroxyalkyl group, prepared by the addition of dibromocarbene to allylic or homoallylic alcohols, undergo an intramolecular reductive carbonylation to the bicyclic lactones 153. bicyclic lactone derived from prenyl alcohol is an important precursor for the synthesis of ris-chrysanthemic acid. (Scheme 54)... 

Armesto, Horspool and coworkers have extensively studied the related rearrangement of /hy-LinsaUiraled imine derivatives, the so-called aza-di-7r-methane rearrangement37. A particularly interesting example is seen by the rearrangement of 75 to 76 (Scheme 19). Adduct 76 furnished chrysanthemic acid following a simple series of steps. It has been... 

For the absolute configuration of the acid moieties, that of chrysanthemic acid was elucidated by Crombie et al. [13] in 1954 and that of chrysanthemum acid was determined by Inoue et al. [14] in 1955, respectively. The absolute configuration of the alcohol moiety was found by Katsuda et al. [15] in 1958. The complete elucidation of the absolute configuration of natural pyrethrins (Fig. 6) has led to the development of new useful synthetic products based on this model. 

Figure 7 shows the course of development of various synthetic pyrethroids developed by retaining chrysanthemic acid as the acid moiety and modifying the alcohol moiety. Numerous useful compounds with favorable characteristics have been derived from the structural modification of natural cinerin I (7). These underlined compounds have been put into practical use as active ingredients, mainly for household insecticides. 

In 1958, Barthel et al. [25] reported dimethrin (15), which was the first substituted benzyl alcohol ester of chrysanthemic acid. This compound was not put into practical use due to its low insecticidal activities. Phenothrin (16), one of the m-phenoxybenzyl alcohol esters developed by Fujimoto et al. [26], was found to have superior chemical stability as well as safety, and has been the sole pyrethroid used as a lice control agent for humans. Further improvement was made by Matsuo et al. [27] who introduced a cyano function at the a position of the benzyl part of phenothrin, leading to a-cyano-m-phenoxybenzyl alcohol esters (17). Thereafter, this alcohol moiety has been used as a component for a number of photostable pyrethroids for agricultural purposes however, the development of cross-resistance can be seen in some pests. 

Transfluthrin (30) [39] is a compound obtained by esterification of dichlorovinyl chrysanthemic acid with 2,3,5,6-tetrafluolobenzylalcohol. With very high insecticidal potency against mosquitoes and flies, it is used as a household insecticide however, as the promotion activity of the compound is known, its use should be restricted to preparations in which the issues of safety for humans and pets have been resolved. 

Allethrin, the first synthetic pyrethroid, is a compound which is the closest in structure to cinerin I. Pyrethroids developed subsequently are mostly esters of chrysanthemic acid, and cinerin II analogs, i.e., esters of chrysanthemum acid have not been industrialized. 

Table 4 Chrysanthemic acid ester (allethrin) and modified chrysanthemum acid ester (allethrin...

Crombie L, Harper SH (1954) The chrysanthemum carboxylic acids. VI. The configurations of the chrysanthemic acids. J Chem Soc 470... 

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