Chrysanthemic acid derivatives, structures

But chrysanthemic acid derivatives are by far not the only examples of cyclopropane-containing structures in nature. In fact, the highly strained three-membered carbocycle is virtually ubiquitous. It occurs, for example, in every green plant in the form of 1-aminocyclopropanecarboxylic acid (ACC) 2, a direct precursor to the plant hormone ethylene [3]. In addition, the cyclopropane unit is found in a variety of other natural products, inter alia in terpenes and in various cyclopropanated fatty acids [4]. The biochemical precursors of the latter are unsaturated fatty acids, and in view of the existence of polyunsaturated fatty... 

Punja et al. (1973) prepared several new esters of chrysanthemic acid, combining structural features of the pyrethroids with those of juvenile hormones. Of these, the JH effect of the most potent derivatives, 57,58 and 59, was nearly the same as that of the natural juvenile hormones. 

Several X-vay structure determinations of three-membered-ring compounds have been reported, including a cyclopropenium salt, 7-PO-substituted norcaradienes (6 X = H, Cl, or Br), chrysanthemic acid derivatives, and 1,6 8,13-cyclopro-panylidene[14]annulene (7). The photoelectron spectrum of (7) has also been reported. ... 

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. 

The copper-catalyzed cyclopropanation of alkenes with diazoalkanes is a particularly important synthetic reaction (277). The reaction of styrene and ethyl diazoacetate catalyzed by bis[/V-(7 )- or (5)-a-phenyl-ethylsalicylaldiminato]Cu(II), reported in 1966, gives the cyclopropane adducts in less than 10% ee and was the first example of transition metal-catalyzed enantioselective reaction of prochiral compounds in homogeneous phase (Scheme 90) (272). Later systematic screening of the chiral Schiff base-Cu catalysts resulted in the innovative synthesis of a series of important cyclopropane derivatives such as chrysanthemic acid, which was produced in greater than 90% ee (Scheme 90) (273). The catalyst precursor has a dimeric Cu(II) structure, but the actual catalyst is in the Cu(I) oxidation state (274). (S)-2,2-Dimethylcyclopropanecar-boxylic acid thus formed is now used for commercial synthesis of ci-lastatin, an excellent inhibitor of dehydropeptidase-I that increases the in vivo stability of the caibapenem antibiotic imipenem (Sumitomo Chemical Co. and Merck Sharp Dohme Co.). Attempted enantioselective cyclopropanation using 1,1-diphenylethylene and ethyl diazoacetate has met with limited success (211b). A related Schiff base ligand achieved the best result, 66% optical yield, in the reaction of 1,1-diphenylethylene and ethyl diazoacetate (275). 

The potentials of this and other similar chiral Schiff base complexes of copper were originally explored for the manufacture of synthetic pyre-throids, a class of highly active pesticides. Cyclopropane rings with asymmetric centers are an integral part of the molecular structures of synthetic pyrethroids. Synthetic pyrethroids were made because the natural product chrysanthemic acid, 7.69, and its derivatives have insecticidal properties. 

Miyamoto J, Nishida T, Ueda K (1971) Metabolic fate of resmethrin, 5-benzyl-3-furylmethyl A -trans chrysanthemate in the rat. Pestic Biochem Physiol 1 293-306 Miyamoto J, Suzuki T, Nakae C (1974) Metabolism of phenothrin (3-phenoxybenzyl A-trans-chrysanthemumate) in mammals. Pestic Biochem Physiol 4 438-450 Moss GP, Derden JC, Patel H, Cronin MT (2002) Quantitative structure-permeability relationships (QSPRs) for percutaneous absorption. Toxicol In Vitro 16 299-317 Mugeng J, Soderlund DM (1982) Liquid chromatographic determination and resolution of the enantiomers of the acid moieties of pyrethroid insecticides as their (-)-l-(l-phenyl)ethylamide derivatives. J Chromatogr A 248(1) 143-149... 

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