Synthetic derivatives of 21-butenyl and related spinosyns
View Patent ↗Macrolide compounds produced by synthetic modification of factors produced by NRRL 30141 have insecticidal and acaricidal activity and are useful intermediates for preparing additional insecticidal and acaricidal compounds
1. A compound of the formulae (1A) or (2A)
wherein
R3 is a group having one of the following formulas (3a) through (3v)
R 4 is H, OH, OR 15 , or ═O;
R 5 is H or CH 3 ;
R 6 and R 7 are H or combine to form a double bond or combine to form an epoxide group;
R 8 in formula (1) is trans-1-butenyl, 1,3-butadienyl, n-butyl, 3-hydroxy-1-butenyl, n-propyl, 1-propenyl, 1,2-epoxy-2-butyl, 3-oxo-1-butenyl, CH 3 CH(OCH 3 )CH═CH—, CH 3 CH(OR 15 )CH═CH—, CH 3 CH═CHCH(CH 2 CO 2 Me)—, or CH 3 CH═CHCH(CH 2 CON(Me 2 ))—
R 9 is H or a group having one of the following formulas (9a) through (9p):
R 15 is C2-C6 alkyl, C3-C6 branched alkyl, C3-C7 cycloalkyl, C1-C6 alkoxy-C1-C6 alkyl, C1-C6 alkylthio-C1-C6 alkyl, halo C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, formyl, C1-C6 alkylcarbonyl, or C3-C6 branched alkylcarbonyl, C3-C7-cycloalkylcarbonyl, C1-C6 alkoxy-C1-C6 alkylcarbonyl, halo C1-C6 alkylcarbonyl, C2-C6 alkenylcarbonyl, C2-C6 alkynylcarbonyl;
R 16 in formula (9m) is C1-C6 alkyl, C1-C6 alkenyl, formyl, C1-C6 alkylcarbonyl, or C3-C6 branched alkylcarbonyl;
n in formula (9n) is an integer from 1 to 4;
provided that at least one of the following conditions is satisfied:
a) R 3 is selected from the group consisting of formulas (3g) to (3v);
b) R 4 is —OCH 3 , —OR 15 or ═O;
c) R 6 and R 7 are H or R 6 and R 7 combine to form an epoxide group;
d) R 8 is propyl, 1,2-epoxy-1-butyl, CH 3 C(O)CH═CH—, CH 3 CH(OCH 3 )CH═CH—, CH 3 CH(OR 15 )CH═CH—, CH 3 CH═CHCH(CH 2 CO 2 Me)—, or CH 3 CH═CHCH(CH 2 CON(Me 2 ))—
e) R 9 is selected from the group consisting of formulas (9j) through (9p);
and provided further that the compound 22,23-dihydro-rham-I is excluded.
2. A compound of claim 1 of formula (1) wherein R 8 is trans-1-butenyl, 1,3-butadienyl, n-butyl, 3-hydroxy-1-butenyl, n-propyl, 1-propenyl, 1,2-epoxy-1-butyl, 3-oxo-1-butenyl, or CH 3 COR 15 CH═CH.
3. A compound of claim 1 wherein R 9 is other than H.
4. A compound of claim 1 wherein the formula and groups R3, R4, R5, R6, R7, R8, and R9 are present in one of the following combinations:
formula
R3
R4
R5
R6
R7
R8
R9
(1A)
H
H
Double bond
1-butenyl
(9a)
(1A)
H
H
Double bond
1-butenyl
(9a)
(1A)
H
H
Double bond
1-butenyl
(9a)
(1A)
(3a)
H
H
Double bond
3-ethoxy-1-butenyl
(9a)
(1A)
(3a)
OC 2 H 5
H
Double bond
1-butenyl
(9a)
(1A)
H
H
Double bond
1-butenyl
(9a)
(1A)
H
H
Double bond
1-butenyl
(9a)
(1A)
H
H
Double bond
1-butenyl
(9a)
(1A)
H
H
Double bond
1-butenyl
(9a)
(1A)
H
H
Double bond
1-butenyl
(9a)
(1A)
H
H
Double bond
1-butenyl
(9a)
(1A)
H
H
Double bond
1-butenyl
(9a)
(1A)
H
H
Double bond
1-butenyl
(9a)
(1A)
H
H
H
H
n-Bu
(9a)
(1A)
H
H
H
H
n-Bu
(9a)
(1A)
H
H
H
H
n-Bu
(9a)
(1A)
H
H
H
H
n-Bu
(9a)
(1A)
H
H
H
H
n-Bu
(9a)
(1A)
H
H
Double bond
3-OEt-1-butenyl
(9a)
(1A)
H
H
Double bond
3-O-nPr-1-butenyl
(9a)
(1A)
H
H
Double bond
3-O-nBu-1-butenyl
(9a)
(1A)
H
H
H
H
1-butenyl
(9a)
(1A)
H
H
H
H
1-butenyl
(9a)
(1A)
H
H
H
H
1-butenyl
(9a)
(1A)
(3a)
H
H
H
H
3-OEt-1-butyl
(9a)
(1A)
H
H
H
H
n-Bu
(9a)
(1A)
H
H
H
H
n-Bu
9(a)
(1A)
H
H
H
H
n-Bu
9(a)
(1A)
(3a)
H
H
H
H
n-Bu
9(a)
(1A)
(3a)
H
H
Double bond
n-Bu
(9a)
(1A)
H
H
Double bond
n-Bu
(9a)
(1A)
(3a)
OH
H
H
H
n-Bu
(9a)
(1A)
(3a)
H
H
H
H
1-butenyl
(9a)
(1A)
(3a)
OH
H
H
H
1-butenyl
(9a)
(1A)
(3a)
H
H
Double bond
n-Pr
(9a)
(1A)
(3a)
H
H
H
H
n-Pr
(9a)
(2A)
(3a)
H
H
H
H
Et
(9a)
(1A)
H
H
H
H
1-butenyl
(9a)
(1A)
H
H
H
H
n-Bu
(9a)
(1A)
H
H
H
H
3-(OC 2 H 5 )-1-butyl
(9a)
(1A)
H
H
H
H
3-(O-nC 3 H 7 )-1-butyl
(9a)
(1A)
H
H
Double bond
CH 3 CH═CHCH(CH 2 CO 2 Me)-
(9a)
(1A)
H
H
Double bond
CH 3 CH═CHCH(CH 2 C(O)NMe 2 )-
(9a)
(1A)
H
H
H
H
3-(O-nC 4 H 9 )-1-butyl
(9a)
(1A)
(3a)
H
H
H
H
3-oxo-1-butyl
(9a)
(1A)
(3a)
H
H
H
H
3-hydroxy-1-butyl
(9a)
(1A)
H
H
H
H
n-Bu
(9a)
(1A)
(3a)
H
—O—
1-butenyl
(9a)
(1A)
(3a)
H
-O-(alpha epoxide)
1-butenyl
H
(1A)
(3a)
H
-O-(beta epoxide)
1-butenyl
H
(1A)
(3a)
H
-O-(beta epoxide)
(9a)
(1A)
(3a)
H
-O-(beta epoxide)
(9b)
(1A)
(3a)
H
-O-(beta epoxide)
1-butenyl
(9b)
(1A)
(3a)
H
H
Double bond
1-butenyl
(1A)
(3a)
H
H
Double bond
1-butenyl
(1A)
(3a)
H
H
H
H
n-Bu
(1A)
(3a)
H
H
Double bond
1-butenyl
(1A)
(3a)
H
H
Double bond
1-butenyl
(1A)
(3a)
H
H
Double bond
n-Bu
(9c)
(1A)
H
Double bond
1-butenyl
(9a)
(1A)
H
Double bond
1-butenyl
(9a)
(1A)
H
Double bond
1-butenyl
(9a)
(1A)
H
Double bond
1-butenyl
(9a)
(1A)
H
Double bond
1-butenyl
(9a)
(1A)
H
H
Double bond
1-butenyl
(9a)
(1A)
H
H
Double bond
1-butenyl
(9a)
(1A)
(3a)
═O
H
Double bond
1-butenyl
(9a)
(1A)
(3a)
H
H
Double bond
3-oxo-1-butenyl
(9a)
(1A)
(3a)
H
H
Double bond
1-butenyl
(1A)
H
H
Double bond
1-butenyl
(9a)
(1A)
(3a)
H
H
H
H
3-oxo-1-butyl
(9a).
5. A compound of claim 4 wherein the formula and groups R3, R4, R5, R6, R7, R8, and R9 are present in one of the following combinations:
formula
R3
R4
R5
R6
R7
R8
R9
(1A)
H
H
Double bond
1-butenyl
(9a)
(1A)
H
H
Double bond
1-butenyl
(9a)
(1A)
H
H
Double bond
1-butenyl
(9a)
(1A)
(3a)
H
H
Double bond
3-ethoxy-1-butenyl
(9a)
(1A)
(3a)
OC 2 H 5
H
Double bond
1-butenyl
(9a)
(1A)
H
H
Double bond
1-butenyl
(9a)
(1A)
H
H
Double bond
1-butenyl
(9a)
(1A)
H
H
Double bond
1-butenyl
(9a)
(1A)
H
H
Double bond
1-butenyl
(9a)
(1A)
H
H
Double bond
1-butenyl
(9a)
(1A)
H
H
Double bond
1-butenyl
(9a)
(1A)
H
H
Double bond
1-butenyl
(9a)
(1A)
H
H
Double bond
1-butenyl
(9a)
(1A)
H
H
H
H
n-Bu
9(a)
(1A)
H
H
H
H
n-Bu
9(a)
(1A)
(3a)
H
H
H
H
n-Bu
9(a)
(1A)
(3a)
H
H
Double Bond
n-Bu
(9a)
(1A)
H
H
Double bond
n-Bu
(9a)
(1A)
(3a)
OH
H
H
H
n-Bu
(9a)
(1A)
(3a)
H
H
H
H
1-butenyl
(9a)
(1A)
(3a)
OH
H
H
H
1-butenyl
(9a)
(1A)
(3a)
H
H
Double bond
n-Pr
(9a)
(2A)
(3a)
H
H
H
H
Et
(9a)
(1A)
H
H
H
H
1-butenyl
(9a)
(1A)
H
H
H
H
n-Bu
(9a)
(1A)
(3a)
H
—O—
1-butenyl
(9a)
(1A)
(3a)
H
-O-(alpha epoxide)
1-butenyl
H
(1A)
(3a)
H
-O-(beta epoxide)
1-butenyl
H
(1A)
(3a)
H
-O-(beta epoxide)
(9a)
(1A)
(3a)
H
-O-(beta epoxide)
(9b)
(1A)
(3a)
H
-O-(beta epoxide)
1-butenyl
(9b)
(1A)
(3a)
H
H
Double bond
1-butenyl
(1A)
(3a)
H
H
Double bond
1-butenyl
(1A)
(3a)
H
H
H
H
n-Bu
(1A)
(3a)
H
H
Double bond
1-butenyl
(1A)
(3a)
H
H
Double bond
1-butenyl
(1A)
(3a)
H
H
Double bond
n-Bu
(9c)
(1A)
H
Double bond
1-butenyl
(9a)
(1A)
H
Double bond
1-butenyl
(9a)
(1A)
H
Double bond
1-butenyl
(9a)
(1A)
H
Double bond
1-butenyl
(9a)
(1A)
H
Double bond
1-butenyl
(9a)
(1A)
H
H
Double bond
1-butenyl
(9a)
(1A)
H
H
Double bond
1-butenyl
(9a)
(1A)
(3a)
═O
H
Double bond
1-butenyl
(9a)
(1A)
(3a)
H
H
Double bond
3-oxo-1-butenyl
(9a)
(1A)
(3a)
H
H
Double bond
1-butenyl
(1A)
H
H
Double bond
1-butenyl
(9a)
(1A)
(3a)
H
H
H
H
3-oxo-1-butyl
(9a).
6. A compound of claim 1 having formula 1A wherein R3 is a group of formula (3h), (3j) or (3k).
7. A compound of claim 6 having formula 1A wherein R15 is ethyl, n-propyl, or i-propyl.
8. A compound of claim 6 having formula 1A wherein R6 and R7 are both H.
9. A compound of claim 1 having formula 1A wherein R6 and R7 are both H.
10. A compound of claim 1 having formula 1A wherein R8 is n-butyl.
11. A compound of claim 1 having formula 1A wherein R6 and R7 combine to form an epoxide group.
12. An insecticide or acaricide composition which comprises an insect, mite, or tick inactivating amount of a compound of claim 3 in combination with a phytologically- or physiologically-acceptable carrier.
13. An insecticide or acaricide method which comprises applying to the locus of an insect, mite, or tick inactivating amount of a compound of claim 3 .
14. A method of protecting a locus from infestation by insects, mites, or ticks which comprises applying to the locus an insect, mite, or tick inactivating amount of a compound of claim 3 .
15. A method of controlling a population of parasites that infest a host animal which comprises administering to the host animal a parasiticidal amount of a compound of claim 3 .
16. A method of protecting a plant from infestation by insects, mites or ticks which comprises applying to the soil an insect or mite inactivating amount of a compound of claim 3 .
17. A method of controlling a population of parasites that infest a host animal which comprises administering to the host animal a parasiticidal amount of a compound of claim 3 .
18. A method of controlling a population of insects which comprises applying to a crop seed an insect-inactivating amount of a compound of claim 3 .
19. A method of controlling a population of insects which comprises administering a compound of claim 3 in combination with a second pesticidal material.
20. A formulation for controlling a lice infestation in a human comprising as an active ingredient a compound of claim 3 , or a physiologically acceptable derivative or salt thereof, and a physiologically acceptable carrier.
21. A method for controlling a lice infestation in a human comprising topically administering a compound of claim 3 to the human.