[CONTRIBUTION FROM
THE
BUREAUOF ENTOMOLOGY AND PLANTQUARANTINE, U. S. DEPARTMENT O F AGRICULTURE]
SOME COMPOUNDS RELATED TO SESAMIN: THEIR STRUCTURES AND THEIR SYNERGISTIC EFFECT WITH PYRETHRUM INSECTICIDES H. L. HALLER, F. B. LAFORGE, AND W. N. SULLIVAN Received December 27, 1941
A number of plant materials have been shown to contain members of a class of compounds having a common nucleus composed of two fused dihydrofuran rings with a substituted pyrocatechin group attached symmetrically to each of one of the carbon atoms adjacent to the ether oxygen atoms. The class includes sesamin (1,2),found in sesame seeds and a minor constituent of sesame oil; asarinin (3, 4)1 found in various oriental plants and in the bark of the American prickly ash ( 5 ) ; pinoresinol(6), a constituent of the exudate of spruce and related species; and eudesamin (7), a constituent of the kino gum from eucalyptus. Within the last few years the chemical investigations of various workers have culminated in the determination of the structure of all these compounds and the establishment of their relation to one another.2 They all contain the same structure with respect to the nucleus, but differ according to the configurational relations on their asymmetric carbon atoms and in the nature of the aromatic substituents. The compounds are represented by formula I.
Hz c\
'\
HC--( /d 0
/-
-)R
I R, R' = OzCHz (methylenedioxyl) for sesamin and asarinin; R = OH, R' = OCH3 for pinoresinol; R, R' = OCH, for eudesamin. The symmetrical structure of compounds represented by this general formula permits the theoretical existence of two optically inactive and two configurationally different active forms together with their optical antipodes ( 6 ) . Natural sesamin, which is dextrorotatory, is partly converted by boiling with alcoholic hydrochloric acid into an isomeric compound, isosesamin. This reaction involves the epimerization of the groups on carbons 1 or 4, is reversible, and results in an equilibrium mixture of isosesamin and sesamin, to whichever of the The name xanthoxylin-S was first given to this compound, but asarinin has been more generally accepted. 2 The literature on this subject is so extensive that only the later references are given. For the most p a r t the articles cited contain references t o previous work.
185
186
HALLER, U F O R G E , AND SULLIVAN
two compounds it is applied. Asarinin is levorotatory and is the optical antipode of isosesamin. Treatment with hydrochloric acid results in an equilibrium mixture of it and Lsesamin (3). The correlation of these compounds with eudesamin and pinoresinol has been established by the conversion of asarinin (levo) to eudesamin (levo) by hydrolysis of the methylenedioxyl groups and methylation of the resulting phenolic derivative (8). By the same process, sesamin (dextro) was converted into pinoresinol dimethyl ether (dextro), the antipode of eudesamin. Epimeric forms of eudesamin and pinoresinol dimethyl ether have been obtained (7). HCl Pinoresinol dimethyl ether [a],= $68"
t-- sesamin
4 isosesamin
[a]D= +68'
[ a ] , = +122'
HC1
Eudesamin [a];= -68'
asarinin [a], = -122'
+-
a Z-sesamin [a],= -68"
The nature of the nucleus in formula I was established in the case of sesamin and asarinin by hydrogenation to the l14-glycolof formula I1 (9),
H
H
I
(C7H70z)CHzC
CCHz (C7H70z)
I I CHzOH CHZOH
I1 which was shown to be the antipode of the reduction product of the naturally occurring hydroxy aldehyde, cubebin, of known structure 111. H H H2(C
:OH'7 HC=O
7
HzCOH HZ0 ) C0 H z
I11 The hydrogenation is interpreted as resulting in cleavage between the oxygen of the ether linkage and the carbon atoms to which the aromatic groups are attached, as shown in IV.
H O
I
I
HC
CH I
I
IV
187
COMPOUNDS RELATED TO SESAMIN
The natural compounds described above and their derivatives and products of rearrangement have lately assumed a practical significance as a result of an important observation made by Eagleson (10). I n experiments on the control of houseflies, Eagleson tested pyrethrum solutions in mixture with a number of vegetable oils, and found that sesame oil, to the exclusion of all others tried, markedly increased the effectiveness of the pyrethrins. On the basis of the known fact that sesame oil contains sesamin, Haller and Goodhue isolated sesamin and prepared pyrethrum sprays to which it had been added. Sullivan then tested these solutions against houseflies by the turntable method and compared them with the solutions of the same pyrethrin content but TABLE 1 SYNERQISTIC EFFECTOF SESAMIN AND RELATED COMPOCNDS O N THE INSECTICIDAL ACTION OF PYRETHRINS AGAINST HOUSEFLIES (Turntable method; 3 tests using about 150 flies per test; solvent, refined kerosene with 10% acetone where needed to increase solubility) ~
MATERIAL
~
CONCENTBATION,
%
AVEBAGE % MORTALITY AFTER.
24 HBS.
I
Sesamin and its isomers: Sesamin . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Sesamin plus pyrethrins. . . . . . . . . . . . . . Isosesamin.. . . . . . . . . . . . . . . . . . . . . . . . . . Isosesamin plus pyrethrins. . . . . . . . . . . . . . Asarinin . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Asarinin plus pyrethrins., . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
~
0.2
4
84 5
~
0.2
+ 0.05
Pinoresinol and derivatives : Pinoresinol . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 0.18 Pinoresinol plus pyrethrins, . . . . . . . . . . . . . . . . . . . . . . . . . . . 0.18 0.05 Dimethylpinoresinol . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 0.2 Dimethylpinoresinol plus pyrethrins. . . . . . . . . . . . . . . . . . . 0.2 0.05 Diacetylpinoresinol . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 0.03 Diacetylpinoresinol plus pyrethrins, . . . . . . . . . . . . . . . . . . . 0.03 0.05 Pyrethrins (checks) : Sample compared with sesamin and its isomers.. . . . . . . . 0.05 Sample compared with pinoresinol and derivatives. . . . . 0.05 ~
~
~
+ + +
87 14 88
1 12 1 17 2 11
25 19
without sesamin and with solutions of sesamin alone (11). These tests showed that, while sesamin alone was without effect, the addition of small quantities of it greatly increased the toxicity of the pyrethrins. It then became of interest to test the other accessible related compounds with respect to their synergistic effect on the pyrethrins. Of the compounds available, and which we have so far prepared, isosesamin and asarinin are most closely related to sesamin. All have the same chemical structure, but differ with respect to the configuration on carbon atoms 1, 2, 3, 4 in formula I, asarinin being the optical antipode of isosesamin. Of the other compounds named, pinoresinol dimethyl ether is, like sesamin, dextrorotatory and differs only with respect to the aromatic substituents, which are veratryl in pinoresinol dimethyl ether and piperonyl in sesamin.
188
HALLER, LAFORGE, AND SULLIVAN
When tested in combination with pyrethrum solutions, isosesamin and asarinin were as effective as sesamin, but pinoresinol dimethyl ether was without appreciable synergistic action, as were pinoresinol itself and its diacetyl derivative. The results obtained are given in Table I. It may be concluded from these experiments that the nature of the substituents on the benzene ring is the only determining factor in the synergistic action of this class of compounds. This conclusion could be further tested by a systematic examination of a larger number of related compounds. The glycols obtained by hydrogenation of sesamin, isosesamin, and asarinin, and the various substitution products of pinoresinol fall into the scope of the investigation, as well as compounds of other structure but containing the piperonyl group. Of such common piperonylic compounds as have been tested, piperonal, safrol, and ethyl piperonylate were ineffective. From the results so far obtained, an important practical field has been opened that may lead to the discovery of other synergists, perhaps more active or more readily available than sesamin or asarinin. WASHINGTON, D . C. REFERENCES (I) BOESEKEN AND COHEN, Biochem. Z., 201,454 (1928). (2) BERTRAM, VAN DER STEUR,AND WATERMAN, Biochem Z . , 197, 1 (1928) (3) HUANG-MINLON, Ber., 70, 951 (1937). (4) KAKU,KUTAMI, AND TAKAHASHI, J . Pharm. SOC. Japan, 66,80 (1936). (5) DIETERLE AKD SCHWENGLER, Arch. Pharm., 277, 33 (1939). (6) ERDTMAN, Suensk Kem. Tid.,48, 230,236,250 (1937). (7) ROBINSON AND SMITH, J . Proc. Roy. Soc. N . S . Wales, 48,449 (1914). ( 8 ) KAKUAND RI, J. Pharm. Soc. Japan, 67,1015 (1937). (9) BRUCHHAUSEN AND GERHARD, Ber., 72,830 (1939). (10) EAGLESON, U. S. Patent 2,202,145, May 28,1940. (11) HALLER, MCGOVRAN, GOODHUE, AND SULLIVAN, see preceding paper.
