Insect Control: Biological and Synthetic Agents - Index of

6 1: Pyrethroids
Table 1 Insecticidal and mammalian toxicity of pyrethrin I and
selected pyrethroids
Pyrethroid
Representative median lethal dose
(mg kg 1 )
Housefly, Musca domestica Rat, oral
Pyrethrin I (1) 30 420
Bioresmethrin (3) 6 800
Permethrin (4) 0.7 2000
Deltamethrin (6) 0.02 100
Table 2 Isomer mixtures of pyrethroids
Pyrethroid Product
Number of
isomers Stereochemistry
Cypermethrin 8 (1R )-cis, aS;
(1S )-cis, aR
(1R )-cis, aR;
(1S )-cis, aS
(1R )-trans, aS;
(1S )-trans, aR
(1R )-trans, aR;
(1S )-trans, aS
Alpha 2 (1R )-cis, aS;
(1S )-cis, aR
Beta 4 (1R )-cis, aS;
(1S )-cis, aR
(1R )-trans, aS;
(1S )-trans, aR
Theta 2 (1R )-trans, aS;
(1S )-trans, aR
Zeta 4 (1R )-cis, aS;
(1S )-cis, aS
(1R )-trans, aS;
(1S )-trans, aS
Cyhalothrin 4 (1R )-cis, aS;
(1S )-cis, aR
(1R )-trans, aS;
(1S )-trans, aR
Lambda 2 (1R )-cis, aS;
(1S )-cis, aR
Gamma 1 (1R )-cis, aS
Fluvalinate 4 (2R), aR; (2R), aS
(2S ), aS; (2S ), aS
Tau 2 (2R ), aR; (2R ), aS
eight isomers but is sold as a mixture of two active
cis/trans isomers, each with the 1R center at C1
and aS in the alcohol moiety.
1.3. Structure–Activity Relationships in
Pyrethroids
As described above, pyrethroids form a diverse class
of insecticides highly effective against a broad spectrum
of insect and acarine pests. The level of activity
is determined by penetration, metabolism within the
insect, and the requirements at the target site. As an
illustration (see Figure 2 for structures), pyrethrin I
has good activity against houseflies but poor activity
against mites, whereas an experimental compound
(29) has very high miticidal but poor insecticidal
activity. Despite this diversity, it is possible to make
some generalizations regarding structural requirements
for high activity in pyrethroids. The sevensegment
model (Figure 3) based on pyrethrin I, the
lead structure originally adopted by Elliott (Elliott
and Janes, 1978), serves as a good model to illustrate
these general requirements and exceptions to them.
Segment A: Unsaturation generally leads to high
activity. However, exceptions are known; for example
fenpropathrin (41), containing the tetramethylcyclopropane
acyl moiety (lacking in unsaturation), has
high insecticidal and acaricidal activity. In general,
large variations (steric and electronic) can be tolerated
in this region. For example, (30) has an extended sidechain
compared with cypermethrin and yet their
activity is similar; flumethrin (8), possessing a bulky
aromatic substituent, is highly active towards ticks.
Segment A þ B: In ester pyrethroids, the gemdimethyl
group or its steric equivalent must be
beta to the ester group. The required geometrical
stereochemistry (cis/trans) across the cyclopropane
ring (segment B) is influenced by the nature of the
alcohol moiety, substituent at C3 and test species.
In general, IR-trans-chrysanthemates (as in bioresmethrin)
are more active then the corresponding
cis isomers. The vinyl dihalo substituents are generally
more effective than the chrysanthemates; however,
the relative activity of the cis and trans isomers
varies considerably. For alcohols containing two
rings (e.g., 3-phenoxybenzyl alcohol as in deltamethrin),
the 1R-cis isomers are generally more active
than the trans isomers, but with alcohol moieties
that contain a single ring (e.g., pentafluorobenzyl
as in fenfluthrin (31) and cyclopentenone as in allethrin)
the converse is true, with the trans isomers
being more active.
In pyrethrin II, the vinyl carbomethoxy group
in the acid moiety has the E configuration. Its corresponding
analogs, cis and trans esters of a-cyano-
3-phenoxybenzyl alcohol, are equally active; the Z
isomer of the nor homolog (e.g., (32)) of the cis
(but not the trans) isomer was unexpectedly much
more active. Acrinathrin incorporates these two features
and, although only half as active as deltamethrin
against houseflies, it is more active towards
some species of mites, ticks, lepidopteran insects,
and sucking pests. Furthermore, stereochemistry
also influences species selectivity of pyrethroids, a
process primarily determined by selective metabolism.
For example, contrary to the above generalization
for pyrethroids containing 3-phenoxybenzyl