Synthetic derivatives of 21-butenyl and related spinosyns
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.