Insect Control: Biological and Synthetic Agents - Index of

210 6: The Spinosyns: Chemistry, Biochemistry, Mode of Action, and Resistance
Table 1 Continued
Number Compound Strain A1 a
62 2 0 ,3 0 ,4 0 -tri-O-ethyl A OEt OEt OEt
63 4 00 -N-ethyl B C Et H
64 4 00 -N-ethyl A B Et
65 4 00 -N-n-propyl A B Prop
66 4 00 -N-n-butyl A B Butyl
67 4 00 -N,N-diethyl C Et Et
68 4 00 -OH A na na
69 5,6,13,14(a)-TH A SB SB
70 5,6,13,14(b)-TH A SB SB
71 13,14-a-DH A SB
72 13,14-b-DH A SB
73 7,11-Dehydro A Me
74 5,6-a-epoxy A a-epoxy
75 5,6-b-epoxy A b-epoxy
76 5,6-DH A SB
77 5,6-DH, 3 0 -O-ethyl A OEt SB
78 5,6-DH, 3 0 -O-n-propyl A OnProp SB
79 A C17-O-acetate A na na
80 A C17-O-DMAA A na na
81 A C17-O-DMAP A na na
82 A C17-O-DMAB A na na
83 A C17-O-NMPipz A na na
84 A C17-O-DMPipd A na na
85 A C9-O-L-lyxose d A
86 A C9-O-L-mannose d A
aPosition on the spinosyn structure (see Figure 1).
bDash indicates no change from substitution pattern for spinosyn A.
c 00 The stereochemistry of 5 -methyl on the forosamine is axial.
d L-Lyxose is missing the 6-methyl of rhamnose; L-mannose is 6-hydroxy-rhamnose.
na, not applicable.; DB, double bond; DMAA, dimethylaminoacetate; DMAB, dimethylaminobutyrate; DMAP, dimethylaminoproprionate; DMPipd,
dimethyl-N-piperidinyl acetate; NMPipz, N-methylpiperazinyl acetate; PSA, pseudoaglycone; SB, single bond; WT, wild type.
containing this naturally occurring mixture is known
as spinosad, the active ingredient in a number of
products (Tracer Õ , Success Õ , SpinTor Õ , Conserve Õ )
marketed by Dow AgroSciences for insect control.
Spinosad received registration from the US Environmental
Protection Agency (EPA) for use in cotton
insect control in February 1997. As discussed
below (see Section 6.5.1.1.1), spinosyn A is the
most active of the naturally occurring spinosyns
from S. spinosa, followed closely by spinosyn D
(Table 2). Thus, the most insecticidally active naturally
occurring spinosyns produced by S. spinosa
are also those that the microorganism naturally
produces in the largest quantity.
Further research around the spinosyns required
the availability of significant quantities of material.
Because the wild-type parent strain only produced
very small quantities of spinosyns, a strain improvement
program was instituted to increase the titers of
the spinosyns produced. During the process of strain
improvement, a number of mutant strains were
identified that had nonfunctional 2 0 - and/or 3 0 -
and/or 4 0 -O-methyltransferases. Since these mutants
were unable to methylate the hydroxyl groups on
A2 R21 R16 R6 R2 0 R3 0 R4 0 5,6 13,14
the 2 0 -, 3 0 -, or 4 0 -positions of the tri-O-methylrhamnose,
a variety of new spinosyns were produced in
addition to a few spinosyns seen only as minor
factors in the wild-type strain (Sparks et al., 1996,
1999).
The mutant strain possessing a nonfunctional 2 0 -
O-methyltransferase produced the already existing
spinosyn H (2 0 -O-demethyl analog of spinosyns A)
as well as several new spinosyns: Q (2 0 -O-demethyl
analog of spinosyn D), R (2 0 -O-demethyl analog of
spinosyn B), S (2 0 -O-demethyl analog of spinosyn E),
and T (2 0 -O-demethyl analog of spinosyn J). Likewise,
a mutant with a nonfunctional 3 0 -O-methyltransferase
produced spinosyn J (3 0 -O-demethyl analog of
spinosyn A), a minor factor in the wild-type strain,
along with the new spinosyns: M (3 0 -O-demethyl
analog of spinosyn B), L (3 0 -O-demethyl analog of
spinosyn D), and N (the 4 0 -N-demethyl analog
of spinosyn L). The mutant possessing a nonfunctional
4 0 -O-methyltransferase produced three new
spinosyns: K (4 0 -O-demethyl analog of spinosyn A),
O (the 4 0 -O-demethyl analog of spinosyn D), and
Y (the 4 0 -O-demethyl analog of spinosyn E) (Sparks
et al., 1996, 1999).