Pyrethroid, synthesis

The production of the chiral cyanohydrin that is used for pyrethroid synthesis as depicted in Fig. 9 is performed using recombinant (S)-HNL from Hevea brasi-liensis. Under the above-mentioned boundary conditions a space-time yield of 1000 g/L/d (ee = 98.5%) is routinely reached. Fig. 10 shows a selection of products, which are currently on the market. 

Pyrethroids are a very potent class of insechcide naturally occurring in chrysanthemums. The cultivation of this plant in Africa is one of the main sources of this insecticide for biological agriculture. A synthetic analog is produced by the use of plant enzymes produced microbially in Escherichia coli. DSM uses the enzyme hydroxynitrilase to produce an intermediate of pyrethroid synthesis by fermentation (Figure 2.4). 

Pyrethroids — Synthesis. 2. Insecticides — Patents. I. Title. II. Series. SB952.P88N38 1990 668 .651-dc20 89-28247 CIP... 

Fujita M, Hiyama T. Highly regio and stereocontrolled halo-genation of l,l-difluoro-2-halo-l-alken-3-ols as applied to polyfluorinated pyrethroid synthesis. Tetrahedron Lett. 1986 27 3659-3660. 

Some of the newer compounds may contain both saturated and unsaturated rings, heteroatoms such as oxygen, nitrogen, or sulfur, and halogen substituents. Others, such as synthetic pyrethroids, may have one or more chiral centers, often needing stereospecific methods of synthesis or resolution of isomers (42). Table 4 Hsts examples of some more complex compounds. Stmctures are shown ia Eigure 1 (25). 

An example of a specialty olefin from an amyl alcohol is Phillips Petroleum s new process for 3-methyl-1-butene (used in the synthesis of pyrethroids) from the catalytic dehydration of 3-methyl-1-butanol (21,22). The process affords 94% product selectivity and 94% alcohol conversion at 310°C and 276 kPa (40 psig). 

This reaction has received especial attention for the stereocontrolled synthesis of polyfluorinated artrfieial pyrethroids [65, 66] (equation 52). 

The work of LaForge and Barthel (24,25) was the prelude to intensive work on synthesis of pyrethroid materials. Some of the synthetic pyrethroids developed are ... 

Within the synthesis of pyrethroids, which are used as insecticides, (5)-4-hydroxy-3-methyl-2-prop-2-ynyl-cyclopent-2-enone is needed. Starting from a racemic mixture of the esterified... 

Developed by Hirano et al. [30], empenthrin (20), the most volatile among the existing pyrethroids, has been in broad practical use as a moth-proofing agent. It is noted that a hint for empenthrin was taken from a-ethynyl furamethrin and acyclic alcohol ester obtained in the course of studies on the synthesis of furamethrin. 

Inouye Y, Takeshita Y, Ohno M (1955) Studies on synthetic pyrethroids V. Synthesis of geometrical isomers of chrysanthemum dicarboxylic acid. Bull Agric Chem Soc Jpn 19 193-199... 

Hirose Y, Nagahori H, Yamada T et al (2009) Comparison of the effects of the synthetic pyrethroid metofluthrin and phenobarbital on CYP2B form induction and replicative DNA synthesis in cultured rat and human hepatocytes. Toxicology 258 64—69... 

The synthesis of compounds 39, 41, and 43 by the ODPM rearrangement opens a novel photochemical route to chrysanthemic acid and other cyclopropane carboxylic acids present in pyrethrins and pyrethroids [52]. In fact, aldehyde 43 can be transformed to tran -chrysanthemic acid by simple oxidation. This new synthetic route to ecologically benign insecticides competes with the one previously described by us using the 1-ADPM rearrangement of p,y-unsaturated oxime acetates [30,53]. 

Many papers from the patent literature on pyrethroids and juvenile hormones cannot be included in this Report. Papers have reported the synthesis and activity of monoterpenoid juvenoids, including geranyl pyridyl ethers " and geranyl alkyl ethers and amines and their epoxides. Further papers in this section include a report of the potent lung toxicity of perillaketone, the observation that the malodorous water contaminant 2-methylisoborneol has the l-R-exo configuration, and that fenchyl methyl L-aspartylaminomalonate is 2 x 10" times sweeter than sucrose. ... 

The method has been applied successfully to synthesis of artificial pyrethroids bearing the HC=C(C1)CF3 moiety143-144. 

Synthesis of Chiral Phenoxybenzaldehyde Cyanohydrin Intermediate for the Synthesis of Pyrethroid Insecticides... 

Scheme 7.22 Synthesis of pyrethroid insecticides via (S)-phenoxybenzaldehyde cyanohydrin.

In the presence of copper(I) chloride, FC-113a adds to silyl enol ethers affording adducts which can be transformed into the /1-chloro-/i-trifluoromethyl enones in moderate yields [100]. The carbon-carbon bond is formed via a free radical addition reaction (Eq. 28). Free radical addition mediated by iron pentacarbonyl was also described recently during a synthesis of a modified pyrethroid [101]. 

Both compounds included here are experimental and in each case the pyridine is a benzene replacement and is not essential for the activity. The urea (103) (79SAP7802440) is a member of a highly active series that kill insects by disrupting the formation of new insect cuticle, through inhibition of chitin synthesis. The cyclopropane ester (104) (78GEP2810881) is a heterocyclic analogue of the pyrethroid insecticides, an extremely successful new class which are active on a wide range of insects. 

Intramolecular cyclopropanation using diazoesters is a powerful synthetic tool. Diazoesters are readily prepared from the corresponding alcohol via House s methods56-57. Numerous examples using the application of this transformation in synthesis have been reported. These include the potent synthetic pyrethroid NRDC 182 (22)58, (1 R)-( )-cis-chrysanthemic acid (23)59, the highly strained bicyclic system 2460, antheridic acid 2561,62 and cycloheptadiene 26 (equations 33-37). 

When the carbinol substituents (R) were the bulky 5-ler -butyl-2-(n-octyloxy)phenyl group, optimum enantioselectivities were achieved with the catalytic use of the corresponding Cu(II) complex (2) in both enantiomeric forms. Specific applications of the Aratani catalysts have included the synthesis of chrysanthemic acid esters (Eq. 5.6) and a precursor to permethrinic acid, both potent units of pyrethroid insecticides, and for the commercial preparation of ethyl (S)-2,2-dimethylcyclopropanecarboxylate (Eq. 5.2), which is used for constructing cilastatin. Several other uses of these catalysts and their derivatives for cyclopropanation reactions have been reported albeit, in most cases, with only moderate enantioselectivities [26-29],... 

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