Journal of Chemical Ecology, Vol. 17, No. 5, 1991

SYNTHESIS A N D FIELD SCREENING OF CHIRAL M O N O U N S A T U R A T E D EPOXIDES AS L E P I D O P T E R A N SEX A T T R A C T A N T S A N D SEX P H E R O M O N E COMPONENTS 1

J.G.

MILLAR,*

M.

GIBLIN, 2 D. BARTON, 2 and E.W.

UNDERHILL

2

Department of Entomology University of California Riverside California 92521 (Received November 16, 1990, accepted January 23, 1991)

Abstract--Enantiomerically enriched forms of (Z)-6-cis-9,10-epoxymonoenes and (Z)-9-cis-6,7-epoxymonoenes of chain lengths C~7_2~ were synthesized by Sharpless asymmetric epoxidation of allylic alcohol intermediates, followed by tosylation or halogenation and chain extension. The resulting monounsaturated epoxides were field tested as sex attractants for lepidopteran species. Euchlaena madusaria Walker males were attracted to blends of the enantiomers of (Z)-6-cis-9,10-epoxynonadecene {6Z-cis-9,10-epoxy-19 : H; IUPAC name [2a,3~(Z)]-2-pentyl-3-(2-dodecenyl)oxirane} in combination with 6Z,9Z-19 : H. The response was antagonized by 9Z-cis-6,7-epoxy-19 :H. 6Z,9Z-19 : H was tentatively identified in pheromone gland extracts. Xanthotype sospeta Dmry male moths were attracted to lures containing 6Z-9S, 10Repoxy- 19:H; the response was antagonized by the opposite enantiomer. Palthis angulalis Hfibner males were attracted to 9Z-6S,7R-epoxy-19:H; the opposite enantiomer was antagonistic. 6Z,9Z-19:H and 9Z-cis-6,7-epoxy19:H and 9Z-cis-6,7-epoxy-19:H were tentatively identified in pheromone gland extracts from Anacamptodes humaria Guenre females. In field trails, 9Z-6R,7S-epoxy-19:H proved to be the attractive enantiomer, and the response was potentiated by 6Z,9Z-19:H. Mechanisms by which unique chemical communication channels are maintained by each species are discussed. Key Words--Sex attractant, pheromone, enantiomer, Lepidoptera, Noctuidae, Geometridae, Euchlaena madusaria, Xanthotype sospeta, Palthis angu*To whom correspondence should be addressed.

Issued as NRCC #32455. 2present address: Plant Biotechnology Institute, National Research Council, 110 Gymnasium Road, Saskatoon, Saskatchewan S7N OW9 Canada. 911 0098-0331/91/0500-09!1506.50/0 9 1991 PlenumPublishingCorporation

912

MILLAR ET AL

lalis, Anacamptodes humaria, (Z,Z)-6,9-nonadecadiene, (Z)-6-cis-9,10(Z)-9-cis-6,7-epoxynonadecene.

epoxynonadecene,

INTRODUCTION

There have been a number of reports of (Z,Z,Z)-3,6,9-trienes and the related cis-3,4-,6,7-, or 9,10-monoepoxydienes as lepidopteran sex attractants and sex pheromone components (compilation to 1986, Arn et al., 1986; Millar et al., 1990a-d, and references therein). There also have been several reports of (Z,Z)6,9-diunsaturated hydrocarbons as sex attractants and pheromones. For example, (Z,Z)-6,9-nonadecadiene (6Z,9Z-19 :H; subsequent abbreviations will follow the same pattern) has been reported as a sex attractant for the geometrid species Bupalus piniaria L. (Bestmann and Vostrowsky, 1982), Boarmia repandata L. (Bogenschiitz et al., 1985), and Alsophila quadripunctata Esp. (Sz6cs et al., 1984), and as a sex pheromone component for Sabulodes caberata Gn. (McDonough et al., 1986). 6Z,9Z-21 :H has been identified in extracts of the pheromone glands of the arctiid moths Utetheisa ornatrix L. (Jain et al., 1983) and Phragmatobia fuliginosa L. (Descoins and Fr6rot, 1984), and the noctuid Mocis latipes Gn. (Descoins et al., 1986). To our knowledge, however, there has been only a single report of a monoepoxide analog of these dienes as a sex attractant or pheromone component; Descoins and Fr6rot (1984) reported 6Z-9S, 10R-epoxy-21 :H as a component of the sex pheromone of the ruby tiger moth, Phragmatobiafuliginosa L. (Lepidoptera: Arctiidae). As an extension of our field screening of (Z,Z,Z)-3,6,9-trienes and the related monoepoxydienes, we have synthesized and field screened racemic and enantiomerically enriched forms of (Z)-6-cis-9,10- and (Z)-9-cis-6,7-epoxymonoenes with carbon chain lengths C17-Czl. We report here: (1) the identification and optimization of sex attractants containing chiral or racemic monoene monoepoxides for four species of noctuid and geometrid moths; (2) the tentative identification by coupled gas chromatography-mass spectrometry with selected ion monitoring of 6Z,9Z-19:H and cis-monoepoxynonadecenes from insect pheromone gland extracts; and (3) the identification of behavioral antagonists which suppress attraction to otherwise attractive lures.

METHODS AND MATERIALS

Insects and Electroantennography Female moths were field collected with sweep nets or in black-light traps. Male moths were collected as described above or in sticky wing traps (Pherotech Inc., Vancouver, British Columbia) containing attractant lures. Field tests

LEPITOPTERAN ATTRACTANTS AND PHEROMONES

913

were carried out in a mixed forest area approx. 100 km north of Saskatoon, Saskatchewan. Sticky wing traps, similar in design to Pherocon 1CP traps (Scentry Inc., Buckeye, Arizona) were used throughout. Traps were hung at heights of approx. 1.5 m, in randomized block design, with traps spaced at least 10 m apart. Survey traps were replicated twice, while specific experiments for a given insect were replicated three or four times. Trap lures consisted of red robber septa (#1780J07, Thomas Scientific, Philadelphia, Pennsylvania) loaded with hexane solutions of test compounds, followed by a few drops of a 10% acetone solution of the antioxidant butylated hydroxytoluene. Lure dosages are listed with the appropriate tables. Summed trap captures were transformed [(X + 1/2) ~/2] and subjected to analysis of variance. Treatments with zero trap captures overall were not included in the ANOVA, as the lack of variance within the treatment captures would violate an assumption of the ANOVA. The variances of the transformed data were tested for homogeneity with Bartlett's test (Sokal and Rohlf, 1981). Significantly different means were separated by Duncan's (1955) multiple range test. Extracts of sex pheromone glands were made by immersion of excised female ovipositor tips in methylene chloride for 20 min. The resulting extracts were concentrated under a stream of N2, and internal standards (heptadecane and tetracosane) were added. The extracts then were analyzed by coupled gas chromatography-electroantennogram detection (GC-EAD) as previously described (Millar et al., 1987) using a DB-1701 capillary column (30 m x 0.32 mm ID, J&W Scientific, Folsom California; temperature program: initial temperature 40~ heat ballistically to 90~ then 4~ to 240~ He carrier gas) or gas chromatography-mass spectrometry. GC-MS analyses were carried out with a Finnigan 4000-E instrument interfaced to an Incos 2300 data system, in electron impact (70 eV) or chemical ionization (isobutane) modes. An Ultra2 capillary column (50 m x 0.32 mm ID, Hewlett-Packard, Avondale, Pennsylvania) was used with helium carrier gas, programming from 40 to 150~ ballistically, then 4~ to 275~ in on-column injection mode.

Synthetic Chemicals The syntheses of the (Z,Z)-6,9-dienes (Underhill et al., 1983) and the geometric isomers of 6Z,9Z-19:H (Miller et al., 1990d) have been described previously. Samples of 3Z,9Z-19:H and 3Z,6Z-19:H were prepared by partial hydroboration of 3Z,6Z,9Z-19 : H with 9-borabicyclononane (9-BBN) in refluxing THF, followed by protonolysis with propionic acid in diglyme at 160~ for 3 hr (Brown, 1975). The resulting mixture was separated cleanly into fractions containing monoenes, dienes, and unreacted triene by flash chromatography on 15 % AgNO3 on silica gel, eluting with 10% ether in hexane.

914

MILLAR ET AL

Glassware was oven-dried at 120~ and cooled under N 2. All reactions were run under a positive pressure of N2. THF was distilled from sodium benzophenone ketyl, methylene chloride was distilled from Call 2, and hexamethylphosphoric triamide (HMPA) was distilled from BaO under reduced pressure. Flash chromatography was performed with 230-400 mesh silica gel (Terochem Laboratories, Edmonton, Alberta). Proton NMR spectra were obtained with a Bruker WM-360 wide-bore instrument, operating at 360 MHz. Infrared spectra were recorded with a Perkin-Elmer 237-B instrument, using neat films on NaC1 plates. Mass spectra (EI, 70 eV) were obtained as described above and are reported as m/z (relative intensity). Optical rotations were measured with a Perkin-Elmer 141 polarimeter, in a l-d, 1 ml cell.

Synthesis of (Z)-6-cis-9 ,10-Monoene Epoxides 2,5-Undecadiyn-l-ol (3). To a solution of 2-octyn-l-ol 1 (6.3 g, 50 mmol) and tosyl chloride (10.1 g, 53 mmol) in dry ether (150 ml) at - 10~ was added in portions over 15 min powdered KOH (250 mmol) (Brandsma, 1971). The resulting slurry was stirred 30 min at 0~ then poured into ice-water (200 ml). The layers were separated, and the aqueous layer was extracted with ether (2 • 50 ml). The combined ether layers were washed with brine, dried (Na2SO4), concentrated, and pumped under vacuum (0.1 torr) to remove traces of solvent. The crude tosylate 2 (13.2 g, 94%) was used without further purification. Ethylmagnesium bromide (approx. 300 mmol) was prepared from Mg turnings (7.3 g, 300 mmol) and ethyl bromide (34 g, 312 mmol) in THF (250 ml). 2-Propyn-l-ol (8.4 g, 150 mmol) was added dropwise over 1 hr, maintaining the temperature < 30~ The resulting slurry was stirred at 20~ for 2.5 hr, then cooled to 0~ and CuI (380 mg, 2 mmol) was added. Tosylate 2 (13.2 g, 47 mmol) in THF (20 ml) was added dropwise, and the mixture was allowed to warm to 20~ then heated at 60~ for 24 hr. The mixture was cooled and poured into 10% aqueous NHaC1 (300 ml), and extracted with ether (1 • 200 ml, 2 • 100 ml). The combined ether layers were washed with brine, dried (Na2SO4), concentrated, and distilled, giving diynol 3 (6.53 g, 84%), bp 96-101~ (0.16 torr), lit, bp 100~ (0.09 torr) (Eiter et al., 1978), as a colorless oil, which yellowed on contact with air. Spectral data matched those previously reported (Eiter et at., 1978). (Z,Z)-2,5-Undecadien-l-ol (4). A solution of P-2 nickel catalyst (Brown and Ahuja, 1973) was prepared by addition of 7.2 ml of a 1 M solution of NaBH4 in EtOH to a solution of Ni(OAc)2 9 4H20 (1.79 g, 7.2 mmol) in 95% EtOH (100 ml), while flushing the reaction flask with N 2. When the effervescence subsided, the flash was flushed with H2, and ethylene diamine (0.96 ml,

LEPITOPTERAN ATTRACTANTS AND PHEROMONES

915

14.4 mmol) was added. The mixture was stirred 10 min, then diynol 3 (5.93 g, 36 mmol) was added, and the flask was maintained under a slight positive pressure of H 2 until the reduction was complete (---6 hr.) The mixture then was filtered through a 1-cm pad of activated charcoal, rinsing the charcoal well with ethanol, and the filtrate was concentrated. The concentrate was taken up in ether (100 ml), washed with 1 M HC1 (50 ml) and brine, dried (Na~SO4) , and concentrated again. The crude dienol was flash chromatographed on silica, eluting with 20% EtOAc in hexane, giving the pure dienol 4 (4.5 g, 74%). The dienol has been previously described only in communications (Gleason et al., 1980; Mills and North, 1983) with no spectral details reported. [~H]NMR (CDC13): 6 5.60 (dtt, 1H, J = 1 0 . 8 , 6.6,1.5 Hz, H-2), 5.51 (dtt, 1H, J = 10.8, 7.2, 1.3 Hz, H-3), 5.40 (dtt, 1H, J ----= 10.7, 7.2, 1.5 Hz, H-5), 5.30 (dtt, 1H, J = 10.7, 7.2, 1.5 Hz, H-6), 4.21 (br. dd, 2H, J = 5, 5 Hz, H-l), 2.81 (m, 2tt, H-4), 2.03 (m, 2H, H-7), 1.4-1.2 (m, 6H, H-8 to H-10), 0.87 (t, 3H, J = 6.8 Hz, H-11). IR (neat) Xmax: 3600-3100 (br. s), 3020 (m), 2965 (s), 2940 (s), 2865 (s), 1020 (br. s) cm -l. MS: 168 (M +, trace), 150 (9.8), 121 (2.2), 107 (4.1), 95 (9.9), 93 (28.6), 91 (16.4), 83 (17.5), 81 (24.3), 80 (83.6), 79 (100), 77 (26.2), 70 (46.4), 67 (55.9), 57 (28.7), 55 (71.8), 54 (35.3), 43 (31.9). (Z)-cis-2,3-Epoxy-undec-5-en-l-oIs (5). To 30 ml of CH2C12 (dried over CaH2) at - 25~ was added sequentially at 20-min intervals with vigorous stirring titanium isopropoxide (3.0 ml, 10 retool), (-)-diisopropyl tartrate (2.6 ml, 12 mmol), dienol 4 (1.73 g, 10.3 mmol), and t-butyl hydroperoxide (4.16 M solution in CH2C12; 5 ml, 20.8 mmol). The solution was sealed and stirred at - 2 5 ~ for one week. The mixture then was worked up by addition of 10% aqueous tartaric acid (25 ml) dropwise over 2 hr, maintaining the temperature at - 2 3 ~ in a CC14/Dry Ice slush bath. The mixture was wanned to 20~ and stirred until the aqueous layer was clear. The layers were separated, and the aqueous layer was extracted with CH2C12 (2 x 20 ml). The combined CH2C12 layers were cooled to 0~ 10% aqueous Na2SO 3 (25 ml) was added dropwise, and the mixture was warmed to 20~ and stirred overnight, to decompose excess t-butyl hydroperoxide. The layers were separated, the aqueous phase was extracted again with CHzC12 (2 • 20 ml), and the combined organic extracts were concentrated. The concentrate was taken up in ether (100 ml), cooled to 0~ 2 N NaOH (150 ml) was added, and the mixture was stirred until all the diisopropyl tartrate had been hydrolyzed ( = 1 hr). The layers were separated, the aqueous phase was extracted with ether (2 x 25 ml), and the combined ethereal extracts were washed with brine, dried (Na2SO4), concentrated, and flash chromatographed on silica (4 cm ID x 20 cm), eluting with 30% EtOAc in hexane. (2R,3S)-Epoxy alcohol 5 was obtained as a clear oil (1.71 g, 90%), [c~]24 = +10.6 ~ (c = 6.32, CH2C12), lit. [c~]2~ = +11 ~ (c = 2.60, CC14)

916

MILLAR ET AL

(Rollin and Pougny, 1986). Spectral data were entirely analogous to those previously reported (Rollin and Pougny, 1986). (2S,2R)-5 was obtained in 76% yield by the same procedure, except that (+)-diisopropyl tartrate was used in the formation of the chiral catalyst; [c~]~ = - 10.9 ~ (c = 9.72, CH2C12), lit. [ot]2n5 = - 10.2 ~ (c 1.5, CHC13) (Mills and North, 1983). The enantiomeric excesses of the two enantiomers of 5 were checked by formation of diastereomeric derivatives (Slessor et al., 1985). Thus, (S)-2-acetoxypropionyl chloride (20/zl) was added to a solution of epoxy alcohol 5 (10 #1) and pyridine (50/~1) in ether (1 ml), and the mixture was stirred 1 hr. The supernatant was pipetted off, washed with water, and dried (Na2SO4). The resulting derivatives were gas chromatographed isothermally on a DB-210 capillary column (30 m x 0.25 mm) at 180~ Baseline separation of the diastereomers was obtained. (2R,3S)-5: ee = 85.7%; (2S,3R)-5: ee = 88.1%. (Z)-l-Iodo-2,3-epoxy-undec-5-enes (6). Iodine (2.16 g, 8.5 mmol) was added to a ice-bath-cooled solution of triphenylphosphine (2.23 g, 8.5 mmol) and imidazole (0.58 g, 8.5 mmol) in ether-CH3CN, 3 : 1 (30 ml), and the resulting slurry was stirred briskly until it was a uniform bright yellow color. (2R,3S)epoxy alcohol 5 (1.53 g, 8.3 mmol) was added in one portion, and the mixture was stirred 1 hr, allowing the mixture to warm to 20~ Pentane (125 ml) then was added, and the mixture was stirred a further 10 min. The top layer was decanted off, and the gummy bottom layer was triturated with pentane (2 x 25 ml). The combined pentane extracts were washed with 1 M Na2S203, dried (Na2SO4) , concentrated, and flash chromatographed on silica (4 cm ID x 20 cm), eluting with 6% ether in pentane. The (2S,3S) iodide 6 (2.43 g, 83 %) was obtained as a pale yellow oil, [ee]~ = - 3 2 . 9 ~ (c = 15.35, CH2C12). [~H]NMR (CDC13): ~i 5.54 (dtt, 1H, J = 10.7, 7.2, 1.4 Hz, H-6), 5.44 (dtt, 1H, J = 10.7, 7.2, 1.4 Hz, H-5), 3.32 (m, 2H, H-I), 3.05 (m, 2H, H-2 and H-3), 2.29 (m, 2H, H-4), 2.04 (dt, 2H, J = 7.2, 7.0 Hz, H-7), 1.5-1.2 (m, 6H, H-8 to H-10), 0.88 (t, 3H, J = 6.8 Hz, H-11). IR (neat): ~kmax 3020 (m), 2965 (s), 2935 (s), 2865, (s), 1450 (s), 1265 (m), 1160 (m) cm -j. MS (CI, isobutane): m/z 295 (M + 1). MS (EI): 223 (M-71, 0.6), 183 (4.5), 155 (5.4), 127 (2.3), 123 (3.7), 111 (9.7), 99 (7.6), 95 (8.2), 93 (7.2), 83 (15.7), 81 (35.4), 79 (16.0), 69 (47.1), 67 (62.5), 57 (55.2), 55 (100), 43 (32.2). (2R,3R)-6 was obtained in 80% yield by the same procedure, [~]22 = +31.9 ~ (c = 4.45, CH2C12), from 2S;3R-5.

(Z)-cis-9,10-Epoxyalk-6-enes (7) {IUPAC Names, [2c~(Z),3c~]-2-(2Octenyl)-3-alkyloxiranes}. The following procedure describes the synthesis of (9S, 10R)-7a from (2S,3S)-6. The syntheses of (9S, 10R)-7b-e were performed under identical conditions, using the appropriate dialkyl lithium cuprate reagents. The syntheses of the (9R, 10S)-Ta-e series were carried out in similar fashion, using (2R,3R)-6. A solution of hexylmagnesium bromide ( = 1.5 mmol), prepared from hexyl

LEPITOPTERAN ATTRACTANTS AND PHEROMONES

917

bromide (248 mg, 1.5 mmol) and Mg turnings (49 mg, 2 mmol) in THF (2.5 ml), was added dropwise by syringe to a mixture of (2S,3S)-6 (200 mg, 0.68 mmol) and CuI (20 mg, 0.11 mmol) in T H F - H M P A (3 : 1, 2.4 ml) maintained at - 2 3 ~ in a CCI4-Dry Ice slush bath. The reaction was stirred 20 min, then quenched by addition of sat. aq. NH4CI (1 ml). The mixture was poured into water (10 ml) and extracted with ether (3 • 5 ml). The combined ether extracts were backwashed with water and brine, dried (Na2SO4), concentrated, and flash chromatographed on silica gel impregnated with AgNO3 (7.5%; 1 cm ID • 20 cm), eluting with 3% ether in pentane. Final purification was achieved by Kugelrohr distillation (0.1 torr, oven temp. - 150~ to remove traces of solvent and chromatographic packing material, yielding (9S, 10R)-7a as a clear oil (96 mg, 56%), [or]2~ = + 3 . 2 ~ (c = 2.29, CH2C12). The [IH]NMR spectrum of (9S, 10R)-Ta was entirely comparable to those of the previously reported analogs, (6Z,9S, lOR)-epoxyheneicosene and (6Z,9S, lOR)-epoxypentadecene (Rollin and Pougny, 1986). The IR spectrum also matched those reported for the analogs; in addition to the previously reported IR absorbtions, we also noted a sharp, medium intensity band at 3020 cm - j (olefinic C-H stretch). MS: 252 ( M + , trace), 243 (0.1), 223 (0.1), 209 (0.3), 195 (0.6), 181 (1.9), 167 (1.3), 153 (2.10, 141 (2.0), 139 (1.8), 127 (3.6), 124 (5.0), 113 (9.2), 110 (14.5), 97 (17.6), 96 (13.9), 95 (27.0), 83 (39.8), 82 (33.8), 81 (57.0), 69 (83.0), 68 (62.0), 67 (76.5), 57 (75.30, 55 (100), 54 (88.1), 43 (62.2). The mass spectra of the higher homologs 7 b - e were characterized by very low intensity molecular ions, a weak M-18 ion, and a series of ions of m/z M29, M-43 . . . . . M-99. The mass spectra in the mass range m/z 43-130 were virtually identical to that of 7a. There were diagnostic fragments at m/z 110 (C4I-I9CH=CH--CH~--CH2) + and 124 ( C s H l l C H = C H - - C H = C H 2 ) + from cleavage and rearrangement of the epoxide, and at m/z 153, from simple cleavage ~ to the epoxide. Optical rotations of (9S, 10R) series: 7b [c~]2o1 = +2.7 ~ (c = 1.97, CH2C12); 7e [ce]21 = + 2 . 6 ~ (c = 0.86, CH2C12); 7d, [c~]2ol = +2.6 ~ (c = 2.22, CH2C12); 7e [~]21 = +2.5 ~ (c = 1.32, CH2C12). (9R,10S) series: 7a, [ot]~I = - 1 . 1 ~ (c = 0.44, CH2C12); 7b, [c~]21 = - 2 . 7 ~ (c = 2.08, CH2C12); 7c, [o~]21 = - 2 . 7 ~ (c = 2.52, CH2C12); 7d, [~]21 = _ 2 . 2 ~ (c = 2.35, CH2C12); 7e, [or 21 = - 2 . 3 ~ (c = 2.15, CH2C12).

Synthesis of (Z)-cis-6, 7-mon-9-ene epoxides (14) {1UPACNames, [2ot,3offZ)]-2-pentyl-3-(2-alkenyl)oxiranes} (Z)-2-octen-l-ol (8). 2-Octyn-l-ol 2 was reduced with 2.5 mmol of P-2 nickel catalyst, prepared as described above in the synthesis of 4. The crude product was distilled, giving (Z)-2-octen-l-ol 8 (5.02 g, 78 %), bp 89-91~ (12 torr); lit bp 98-102~ (10-15 torr) (Osbond, 1961).

918

MILLAR ET AL

cis-2,3-Epoxy-octan-l-ols (9). The recently reported modification of the Sharpless asymmetric epoxidation method, 1 using molecular sieves, was attempted. Thus powdered 4 ,~ molecular sieves (5 g, freshly activated) were added to CH2C12 (40 ml) at - 2 3 ~ (CC14-Dry Ice slush bath). To this mixture was added sequentially at 20-min intervals titanium isopropoxide (0.6 ml, 2.0 mmol), (+)-diisopropyl tartrate (0.54 ml, 2.5 mmol), alcohol 8 (2.45 g, 19.4 mmol), and t-butyl hydroperoxide (4.75 M in CH2C12; 8.5 ml, 40 mmol). The mixture was stirred at - 2 5 ~ for 40 hr. The reaction was worked up by addition of aq. tartaric acid (10%, 10 ml) over 1 hr, while stirring vigorously and maintaining the temperature at - 2 3 ~ Stirring at this temperature was continued for 1 hr, then the mixture was allowed to warm to 20~ and stirred another 2 hr. The mixture then was filtered with suction through a bed of Celite (4 cm). The layers were separated and the aqueous phase was reextracted with CH2C12 (2 • 10 ml). The combined CH2C12 extracts were cooled to 0~ and aq. Na2SO 3 (1.3 g in 10 ml H20) was added dropwise over 30 min. The resulting mixture was warmed to 20~ and stirred overnight. The layers were separated, and the aq. phase was extracted again with CH2C12 (2 • 10 ml). The combined organic extracts were washed with brine, dried (Na2SO4), concentrated, and flash chromatographed on silica gel (4 cm ID • 20 cm), eluting with 30% EtOAc in hexane, yielding (2S,3R)-9 (1.73 g, 62%), [c~]21 = - 5 . 4 2 ~ (c = 9.08, CH2C12). [IH]NMR (CDC13): 6 3.83 (ddd, 1H, J = 12.0, 7.3, 4.1 Hz, H-I), 3.66 (ddd, 1H, J = 12.0, 6.8, 4.8 Hz, H-I'), 3.13 (dt, 1H, J = 6.8, 4.2 Hz, H-3), 3.01 (m, 1H, H-20, 1.67 (dd, 1H, J = 7.3~ 4.8 Hz, OH), 1.671.25 (m, 8H, H-4 to H-7), 0.88 (br. t, 3H, J = 7 Hz, H-8). IR (neat): 36003100 (br. s), 2965 (s), 2940 (s), 2965 (s), 1460 (m), 1380 (w), 1040 (s) cm -j. MS: 113 (0.2, M-31), 95 (0.8), 84 (2.5), 83 (37.7), 71 (3.6), 69 (5.2), 67 (3.1), 61 (4.2), 57 (28.2), 56 (18.0), 55 (100), 45 (17.2), 43 (73.8). The enantiomeric excess was determined by formation of diastereomeric derivatives of the alcohol with (S)-2-acetoxypropionyl chloride (Stessor et al., 1985), as described above for compounds 6. Baseline separation of the derivatives was obtained on a DB-210 capillary column (30 m x 0.25 mm) operated isothermally at 150~ Ee of (2S,3R)-9: 74.6%. The (2R,3S) enantiomer was prepared concurrently in similar fashion in 75% yield, using (-)-diisopropyl tartrate in the asymmetric epoxidation step; [c~]21 = +5.61 ~ (c = 9.65, CH2C12), ee 76.1%. Mass, NMR, and IR spectra were satisfactory. The (2R,3S) enantiomer has been previously reported in a communication (Nicolau and Webber, 1985). 1-Iodo-cis-2,3-epoxy-octanes 10. The iodides 10 were prepared exactly as described above for the iodides 6. The purified products were also vacuum i Referredto in an AldrichChemicalCo. advertisementon the back coverof./. Org. Chem. 50(25), 1985; R.M. Hanson, S.Y. Ko, J.M. Chang, and K.B. Sharpless, unpublished results.

LEPITOPTERAN ATTRACTANTS AND PHEROMONES

919

distilled, Kugelrohr over temperature 75~ (0.1 torr), yielding, for example (2R,3R)-10 (2.38 g, 88%), [a]~~ = +35.3 ~ (c = 9.41, CH2C12). [1H]NMR(CDC13): 6 3.29 (m, 2H, H-I), 3.05 (m, 1H, H-3), 2.98 (m, 1H, H2) 1.6-1.4 (m, 4H, H-4 and H-5), 1.38-1.27 (m, 4H, H-6 and H-7), 0.89 (t, 3H, J = 7.0 Hz, H-8). IR (neat): 2965 cm (s), 2935 (s), 2870(s), 1460 (s), 1380 (m), 1265 (m), 1165 (s) cm -~. MS: 254 (0.2), 183 (1.0), 171 (t.5), 155 (4.3), 141 (2.4), 127 (56.7), 83 (73.3), 57 (100), 55 (96.5), 43 (75.2). Isobutane CI-MS: m/z 255 (M + 1). The (2S,3S) enantiomer was prepared in identical fashion in 92% yield, [c~]~I = -36.5 (c = 6.26, CH2C12). Mass, NMR, and IR spectra were satisfactory. (Z)-cis-6, 7-epoxyalk-9-enes 14. The alkenyl bromides 12a-e were prepared from 1-alkynes 11, exactly as previously described (Millar and Underhill, 1986). The following procedure describes the synthesis of (6R,7S)-14a from (2R,3R)-epoxyiodide 10. The syntheses of (6R,7S)-14b-e were performed under identical conditions, using the appropriate alkenyl Grignard reagents 13b-e. The syntheses of the (6S,7R)-14a-e series were carried out in similar fashion, using (2S,3S)-10. Grignard reagent 13a was prepared by slow addition of (Z)-l-bromonon1-ene 12a (620 mg, 3.0 mmol) to Mg turnings (120 mg, 5 mmol) in THF (6 ml) at 20~ and stirring for 2 hr. The Grignard solution was added dropwise over 10 min to a stirred solution of (2S,3S)-10 (381 mg, 1.5 retool), CuI (29 mg, O. 15 mmol), and HMPA (1.4 ml, 6 mmol) in THF (2 ml) at - 2 3 ~ (CC1aDry Ice slush bath). The resulting mixture was stirred for 30 rain at - 2 3 ~ then poured into 10% aq. NH4C1 (25 ml), and extracted with hexane (1 x 25, 2 x 10 ml). The combined hexane extracts were washed with water and brine, dried (Na2SO4), and filtered with suction through a plug of silica gel (4 cm), rising the silica well with ether. The filtrate was concentrated and flash chromatographed on AgNO3-impregnated silica gel (7.5%; 2 cm ID • 20 cm), eluting with 2.5% ether in hexane. The purified compound was then freed from traces of column packing by vacuum distillation, Kugelrohr oven temperature 140~ (0.05 Torr), yielding (6R,7S)-14a (228 mg, 60%), [~]~4 = +2.86 ~ (c = 1.99, CH2C12). [IH]NMR(CDC13): 6 5.51 (dtt, 1H, J = 10.8, 7.8, 1.2 Hz, H-10), 5.40 (dtt, 1H, J = 10.8, 7,2, 1.2 Hz, H-9), 2.91 (m, 2H, H-6 and H7), 2.45 (m, 1H, H-8), 2.36 (m, 1H, H-8'), 2.02 (br. dt, 2H, J = 6.8, 6.8 Hz, H-11), 1.5-1.2 (m, 10H, H-12 to H-16), 0.88 (m, 6H, H-1 and H-17). IR (neat): 3920 (m), 2970 (s), 2935 (s), 2865 (m), 1460 (m), 1380 (m) cm -1. MS: 252 (0.2, M+), 234 (0.4), 209 (0.4), 196 (0.3), 195 (0.2), 181 (1.4), 167 (1.3), 153 (2.1), 141 (2.9), 138 (3.2), 123 (2.4), 113 (6.50, 110 (8.0), 99 (15.40, 97 (14.6), 96 (15.10, 95 (16.10, 83 (32.6), 81 (33.1), 71 (19.60, 69 (38.7), 68 (36.8), 67 (52.2), 57 (40.50, 55 (92.2), 54 (50.9), 43 (100).

920

MILLARET AL

The mass spectra of 14b-e were characterized by small but distinct ions at M § M-18, M-43, M-56, M-111, M-142, and m/z 113. The mass spectra were otherwise very similar to that of 14a. NMR and IR spectra were all satisfactory. Optical rotations of 6R,7S series. 14b, [o~]24 = +2.51 ~ (c = 1.95, CH2C12); 14c [Ot]2D4 = +2.34 ~ (c = 1.97, CH2C12); 14d, [o~]24 = +2.32 ~ (c = 1.99, CH2C12); 14e, [o~]2o 4 = + 1.78 ~ (c = 2.08, CH2C12). (6S,7R) series: 14a, [ot]2o4 = - 2 . 8 3 ~ (c = 0.92, CH2C12); 14b, [c~]2o4 = +2.45 ~ (c = 1.68, CH2C12); 14c, [cz]24 = +2.35 ~ (c = 2.04, CH2C12); 14d, [c~]~ = +1.92 ~ (c = 1.98, CH2C12); 14e [ot]~4 = +2.12 ~ (c = 2.03, CH2C12).

RESULTS

Euchlaena madusaria Walker. Male E. madusaria moths were first caught in 1985. Traps baited with 6Z-cis-9,10-epoxy-19 : H (replicated three times, 500 #g dosage) caught 89 specimens, while the corresponding traps baited with 9Zcis-6,7-epoxy-19:H, the combined monoepoxide mixture from nonspecific monoepoxidation of 6Z,9Z-19 : H or 6Z, 9Z-19 : H caught no moths. This experiment conclusively demonstrated that 6Z-cis-9,10-epoxy-19:H was an attractant for this species, and that the 9Z-cis-6,7 regioisomer was antagonistic, as the mixture of monoepoxides caught no moths. Pheromone gland extracts (one, two, and three female equivalents) from field-collected female moths were analyzed by coupled gas chromatographyelectroantennogram detection (GC-EAD) using a DB-1701 column. Male antennae consistently responded to a compound at the retention time of 6Z-cis9,10-epoxy-19: H with a weaker response to a compound at the retention time of 6Z,9Z-19:H. On this column, 6Z-cis-9,10-epoxy-19:H was separated cleanly from the 9Z-cis-6,7-epoxy-19 :H regioisomer, and a standard sample composed of 3Z,6Z-19 : H, 3Z,9Z-19 : H, and 6Z,9Z-19 : H gave three clearly resolved peaks (relative retention times versus heptadecane: 6Z,9Z-19:H, 1.226; other two isomers, 1.236 and 1.251) providing additional proof of the position of the double bond. It had been demonstrated previously that all the geometric isomers of 6,9-nonadecadiene also were resolved cleanly under the standard GC-EAD conditions (Millar et al., 1990d). A pheromone gland extract from two females was analyzed by coupled gas chromatography-mass spectrometry (GC-MS) using an Ultra-2 capillary column, in selected ion mode, with isobutane chemical ionization (CI). A perfect retention time match, and a good ion ratios fit with three ions was obtained for 6Z,9Z-19 : H vs. a 400 pg standard [standard, m/z (rel. abundance): 264 (100 M+), 263 (87, M-I), 155 (11); unknown from insect extract: m/z 264 (100), 263 (96), 155 (13)]. The corresponding monoepoxide was not detected.

LEPITOPTERAN ATTRACTANTS AND PHEROMONES

921

A field test in 1986 (replicated three times) indicated that E. madusaria males were not attracted to either enantiomer of 6Z-cis-9,10-epoxy-19:H (one moth caught in traps with 9R,10S enantiomer; 0 moths with 9S,10R enantiomer), while the racemate was highly attractive (136 moths caught). Further field tests demonstrated that E. madusaria males were optimally attracted to mixtures of the enantiomers of 6Z-cis-9,10-epoxy-19 : H (Table 1), with the most attractive lures containing a 1:1 or 4:1 blend of the (9S,10R) and (9R, 10S) enantiomers, respectively. Finally, in an experiment run late in the flight season of this moth, traps (replicated three times) baited with a 4 : 1 blend of 6Z-cis-9,10-epoxy-19 : H 6Z,9Z-19:H caught significantly more moths (23 specimens) than traps baited with 6Z-cis-9,10-epoxy-19:H alone (five specimens), suggesting that 6Z,9Z19 : H may potentiate the response to the epoxide. Xanthotype sospeta Drury. This species is sympatric with and has approximately the same flight season as E. madusaria. A preliminary field test indicated that the X. sospeta males were selectively attracted by 6Z-9S, 10R-epoxy19:H, as traps (replicated three times) containing this compound caught 17 specimens, while the corresponding traps containing the opposite enantiomer or the racemate caught none. This selectivity was confirmed in further field tests (Table 1), wherein only traps containing a high proportion of the 9S, 10R enantiomer caught moths. Thus, the data suggest that 6Z-9S, lOR-epoxy-19:H is a powerful attractant for this species, and that the (9R, 10S) enantiomer antagonizes the attractive response. Palthis angulalis Habner. Males of this species were first captured in 1984

TABLE 1. CAPTURES OF Euchlaena madusaria AND Xanthotype sospeta IN TRAPS BAITED WITH BLENDS OF ENANTIOMERSa OF (Z)-cis-9,10-EPOXVNONADEC-6-ENE

Lure blend 6Z-9R, 10Sepoxy-19 : H (#g)

6Z-9S, 10Repoxy-19 : H (t~g)

500 475 400 250 100 25 0

0 25 100 250 400 475 500

Males captured (X + SE) ~'

E. madusaria

2.0 15.3 52.7 47.7 18.3

0 __+0.6c ___ 5.8bc _+ 10.7a + 11.9a + 0.% 0

X. sospeta 0 0 0 0 0 3.7 ___ 1.2a 19.0 + 7.8a

Enantiomeric excess of 6Z-9R, 10S-epoxy-19 : H, 88.1%, 6Z-9S, 10R-epoxy-19 : H, ee 85.7 %. bTraps replicated three times. Traps were set out from June 26 to July 16, 1986. Trap captures followed by the same letter are not significantly different (P > 0.05).

922

MILLAR ET AL

in several traps containing the combined monoepoxides mixture from nonspecific oxidation of 6Z,9Z-19 : H as the major component (up to 22 moths caught/ lure). A 1985 field experiment (replicated three times) indicated that the 9Z-cis6,7-regioisomer was the attractive component, as traps containing this compound (250 tzg) caught 16 specimens, while traps containing the 6Z-cis-9,10regioisomer (250/zg) caught none. In addition, traps containing the combined monoepoxides mixture (500/zg) caught 16 specimens, indicating that the 9Zcis-6,7-19:H regioisomer was not antagonistic. An experiment in 1986 demonstrated that 9Z-6S,TR-epoxy-19:H was the more attractive enantiomer, as traps (N = 3) containing this compound (250 tzg) caught 39 specimens, while the corresponding traps containing 9Z-6Z,7Sepoxy-19 : H (250/xg) caught one specimen. Anacamptodes humaria GuenOe. A number of specimens of A. humaria (37) were caught in 1986 field survey traps (replicated twice) containing a 1 : 1 blend of 9Z-6R,TS-epoxy-19:H (250 #g) with 6Z,9Z-19 : H (250/zg). The corresponding traps containing the opposite enantiomer (6S,7R) in combination with 6Z,9Z-19: H caught no moths. When present as a single component, 9Z6R,7S-epoxy-19:H caught 10 specimens, while the corresponding traps containing either 9Z-6S,7R-epoxy-19 :H, 6Z,9Z-19 : H, or 9Z-cis-6,7-epoxy-19 :H as single components caught no moths. 6Z,9Z-19:H and 9Z-cis-6,7-epoxy-19:H were tentatively identified by selected ion monitoring (SIM) GC-MS analysis of the pheromone gland extract from three field-collected female moths on an Ultra-2-capillary column. Perfect retention time and good ion ratios matches were made for 6Z,9Z-19 : H [400 pg standard, m/z 264 (89, M+), 263 (100, M-I), 155 (14); unknown from insect extract: 264 (100), 263 (95), 155 (14)] and 9Z-cis-6,7-epoxy-19:H [standard, m/z 281 (100, M + 1), 279 (4, M-I), 263 (22, M + 1-18), 155 (1); unknown from insect extract: 281 (100), 279 (4), 263 (22), 155 (0)]. The lack of a sizable ion at m/z 155 was significant, as the 6Z-cis-9,10-epoxy-19:H regioisomer, which has a retention time very similar to that of 9Z-cis-6,7-epoxy-19:H, has a strong diagnostic ion at m/z 155 (40% of the m/z 281 base peak). Thus, the field data and the analyses of pheromone gland extracts both implicate 9Z-6R,7Sepoxy-19 : H and 6Z,9Z-19 :H as sex pheromone components of this species. Synthesis. The (Z)-cis-9,10-epoxymono-6-enes were prepared by the route outlined in Scheme 1. This route was similar to those which had been used to synthesize the enantiomerically enriched forms of the analogous (Z,Z)-3-6-cis9,10-epoxydienes (Mori and Ebata, 1981, 1986; Wong et al., 1985). The stoichiometric version of the Sharpless asymmetric epoxidation was used (Katsuki and Sharpless, 1980), resulting in enantiomeric excesses of approximately 88 %. The enantiomeric excesses of the resulting epoxy alcohols 5 were determined by esterification of the alcohols with (2S)-2-acetoxypropionyl chloride (Slessor et al., 1985), and separation of the resulting diastereomeric derivatives by cap-

923

LEPITOPTERAN ATTRACTANTS AND PHEROMONES

illary GC on a DB-210 column. The epoxyalcohols 5 were converted to iodides 6 (Garegg and Samuelsson, 1980; Corey et al., 1983), and the syntheses were completed by the dropwise addition of a THF solution of the appropriate alkylmagnesium bromide (2 equiv) to a cooled ( - 2 3 ~ slurry of iodide (1 equiv), CuI (0.1 equiv), and HMPA (4 equiv) (Millar and Underhill, 1986; Nicolaou et al., 1984). The epoxides 7 were obtained in approx. 25 % overall yield from 2-octyn-1-ol 1. The reaction was sensitive to conditions (Nicolaou et al., 1984), as attempted alkylation of the iodides in ether by addition of dialkyllithium cuprates, as had been reported for 1-tosyloxy-2,3-epoxyalkenes (Mori and Ebata, 1981, 1986; Wong et al., 1985) gave almost exclusively the rearrangement product (Z)-l,5-undecadien-3-ol. The synthetic route to the enantiomerically enriched forms of the (Z)-cis6,7-epoxymono-9-enes was similar to that which we had used in the synthesis of the analogous (Z,Z)-3,9-cis-6.7-epoxydienes (Millar and Underhill, 1986), as shown in Scheme 2. However, the catalytic modification of the key Sharpless asymmetric epoxidation step using powdered molecular sieve (Hanson and ox 2: X = Tosyl

m

1 ~

OH

4

L 5: X = O H 6: X = I

1 7a: R = C6H13 b: R = C?Hls ~: R = C8H17 d: R = C9H19 ~: R = CloH21 SCHEME 1

924

MILLAR ET AL

Sharpless, 1986), the details of which were at the time unpublished (see footnote 1, p. 917) was tried, resulting in a much faster reaction but with a somewhat lower enantiomeric excess (approx. 75 % ee). The epoxy alcohols were subsequently converted to the (Z)-cis-6,7-epoxymono-9-enes according to the previously reported methods used in synthesizing the epoxydiene analogs (Millar and Underhill, 1986). Overall yields were approximately 25 %.

DISCUSSION In parallel with the increasing number of identifications of pheromones and sex attractants that are derived from epoxidation of (Z,Z,Z)-3,6,9-trienes, it was reasonable to expect that there may be analogous sets of monounsaturated monoepoxides with sex attractant activity. The work reported here confirms this expectation. The identification of 9Z-6S,7R-epoxy-19 : H as a sex attractant for the noctuid species P. angulalis is the first report of a (Z)-cis-6,7-epoxymono-9-ene as an insect sex attractant. It was to be expected that compounds such as these would be identified eventually as sex attractants and pheromones, as the cor-

9--

/OH

1

1 ~

.

~

*

~

~

-

0 H

~..

~--

o ~ . ~ , . ~ l

~_: l =OH 10:

X =1

Y ~

R

R

11

12:

Y =Br

13:

Y =

MgBr

I 14a:

R = C7H15

IZ.: R = Cell17

o

c:

R = C9H19

~t:

R = C10H21

it: R = C l l H 2 3 SCHEME 2

LEPITOPTERAN ATTRACTANTS AND PHEROMONES

925

responding (Z,Z)-6,9-dienes and analogous diene monoepoxides had been reported from a number of lepidopteran species (references in Introduction). To our knowledge, this is the second report of (Z)-cis-9,10-epoxymono6-enes as sex attractants and possible sex pheromone components for geometrid moth species; 6Z-cis-9,10-epoxy-21 :H has been reported as an attractant for the geometrid Caustoloma flavicaria L. (Kovalev and Nikolaeva, 1986). The same compound has been identified as a sex pheromone component for the arctiid moth Phragmatobiafuliginosa L. (Descoins and Frrrot, 1984), and the chirality of the epoxide was presumed to be 9S,10R based on electroantennographic responses to the analogous 3Z,6Z-9S, lOR-epoxy-21 :H (Rollin and Pougny, 1986). The biologically active compounds described here were discovered by field screening of potential attractants and optimized using information from GCEAD analyses of standard mixtures and of pheromone gland extracts. There are several clear indications of the intricate balance of attraction and behavioral antagonism, with the chirality of the epoxide components playing a crucial role, as was found with the diene monoepoxide analogs (Millar et al., 1990a-d, 1991a). The results are summarized in Table 2. Distinct communication channels may be maintained by a combination of synergism between components, blend ratio, and antagonism in the cases of blends sharing common components. For example, E. madusaria males were attracted only by blends of the enantiomers of 6Z-cis-9,10-epoxy-19 : H. This represents one of several known examples of enantiomeric synergism in the lepidoptera (Wong et al., 1985; Millar et al., 1991a).

TABLE 2. BIOLOGICAL ACTIVITIES OF COMPOUNDS TESTED AGAINST FOUR LEPIDOPTERAN SPECIES

Compounds"

Species E. X. P. A.

madusaria sospeta angulalis humaria

6Z,9Z- 19 : H P

P

6Z9R, 10Sepoxy19 : H

6Z9S, 10Repoxy19 : H

A I

A A

9Z-6R,7Sepoxy-19 : H

9Z-6S,7Repoxy-19 : H

I

I

I(?) P

A

up = component tentatively identified from pheromone gland extracts; A = sex attractant; I = compound inhibiting attraction.

926

MILLAR ET AL

The sympatric species, X. sospeta, was attracted to only one of the enantiomers, with the opposite enantiomer being a strong antagonist (Table 2). Thus, these two species were not attracted to the same lures. In similar fashion, P. angulalis was attracted to lures containing the single component 9Z-6S,7R-epoxy-19:H, while A. humaria was attracted by blends of the opposite enantiomer in combination with 6Z,9Z-19 :H (Table 2). There is considerable but not conclusive evidence to support the tentative identification of 6Z,9Z-19 :H and 6Z-cis-9,10-epoxy-19:H as sex pheromone components for E. madusaria. For 6Z,9Z-19 : H, this evidence consists of exact retention time matches on two capillary GC columns versus a synthetic standard, a good SIM ion ratios match versus a standard, and biological activity in terms of electroantennographic responses and attractant activity in the field. Furthermore, it has been shown that the other geometric isomers of this compound have retention times different from that of 6 Z , 9 Z - 1 9 : H under the GC conditions used (Millar et al., 1990d), and we have shown here that the 3Z,6Z19 :H and 3Z,9Z-19 : H positional isomers, which might also be potential pheromone candidates, also have retention times different from 6Z,9Z-19: H under the GC-EAD conditions used. In addition 6Z,9Z-19 : H is a logical biosynthetic precursor to the attractive 6Z-cis-9,10-epoxy-19 :H. However, on the basis of the available data, we cannot absolutely rule out the slim possibility that the insect-produced compound is actually a positional isomer of 6Z,9Z-19 : H. The evidence for 6Z-cis-9,10-epoxy-19 :H is more tenuous. A compound in the female pheromone gland extract that gave strong electroantennogram activity exactly matched the retention time of a synthetic standard. The biological activity in the field, coupled with the demonstrated behavioral antagonism of the 9Z-cis-6,7-epoxy-19:H regioisomer, also provided circumstantial evidence for this compound being a pheromone component for E. madusaria. There was reasonably conclusive evidence that 6Z,9Z-19:H and 9Z-6S,7Repoxy-19 : H are female-produced pheromone components of the species Anacamptodes humaria. Both compounds were identified in pheromone gland extracts by a combination of GC retention time matches, and by matches of SIM chemical ionization mass spectra with those of standards. In light of the retention time match with a standard, the possibility of the diene insect-produced compound being an isomer other than 6Z,9Z-19 : H is small, as described above for E. madusaria.

Synthesis Three syntheses of a component of the sex pheromone blend of the ruby tiger moth, 6Z-cis-9,10-epoxy-21 :H, or its enantiomers have been reported. In the first, Rollin and Pougny (1986) synthesized the 9S,10R enantiomer in 10

L E P I T O P T E R A N A T T R A C T A N T S AND P H E R O M O N E S

927

steps from D-xylose, providing material of high chiral purity. However, the last step delivered a 9 : 1 mixture of the 6Z: 6E geometric isomers. In addition, the synthesis was only amenable to the production of the 9S, 10R enantiorner or series of homologous enantiomers. Ebata and Mori (1989) described a synthesis of both of the enantiomers of 6Z-cis-9,10-epoxy-21 :H, using Sharpless asymmetric epoxidation of the achiral intermediate (Z)-tetradecen-2-ol as a key step. Repeated recrystallization of crystalline derivatives of the intermediate epoxy alcohols was used to increase the chiral purities to high levels. However, this synthetic route could only be used to produce the Clt compounds, that is, it could not be used to efficiently and convergently synthesize homologs. It also must be mentioned that the optical rotations reported for the tiger moth pheromone component 6Z-9S, 10R-epoxy-21 :H by both Rollin and Pougny (1986) ([a]~~ = +5.5 ~ and Ebata and Mori (1989) ([c~]23 = +9.4 ~ are considerably different from each other, and from our result ([a] 2~ = +2.5 o). Rollin and Pougny indicated that their product was contaminated with 10 % of the 6E isomer, and this or other impurities may have contributed to a possibly erroneous optical rotation. Possible impurities in the pheromone prepared by Ebata and Mori (1989) may have had a similar effect. Bell and Ciaccio (1988) published a short synthesis of racemic 6Z-cis-9,1 Oepoxy-21 :H based on an ingenious alkylative rearrangement of an epoxytosylate intermediate. With several minor modifications, this synthesis could be adapted to the production of either enantiomer of this compound or to the production of homologs. Our synthetic strategies were designed to satisfy two criteria. First, we wanted facile access to both enantiomers of each monoene epoxide. This was expeditiously accomplished by use of the Sharpless asymmetric epoxidation sequence on appropriate readily available allylic alcohol precursors. Although this procedure gives enantiomeric excesses of approximately 90% at best (i.e., a 19:1 ratio of enantiomers) for 1,2-disubstituted allylic alcohol subtrates (Katsuki and Sharpless, 1980), our previous experiences with the analogous diene monoepoxides had demonstrated that compounds of this enantiomeric purity were in many cases sufficient to demonstrate that biological activity, either as an attractant or a behavioral antagonist, could be attributed to one of the two enantiomers. Our second requirement was for a synthetic route that would be amenable to the efficient production of homologous series of compounds, that is, for syntheses that used a common intermediate to which a chain of variable length could be attached in the penultimate step. The chiral epoxy alcohols obtained by the Sharpless epoxidations, when converted to epoxy iodides, fulfilled this requirement.

928

MILLAR ET AL REFERENCES

ARN, H., TOTH, M., and PRIESNER, E. 1986. List of sex pheromones of Lepidoptera and related attractants. OILB-SROP/IOBC-WPRS, Secr6tariat General, 149 Rue de Bercy, F-75595 Paris cedex 12; ISBN 92-9067-002-9. BELL, T.W., and CIACCIO, J.A. 1988. Alkylative epoxide rearrangement. Application to stereoselective synthesis of chiral pheromone epoxides. Tetrahedron Lett. 29:865-868. BESTMANN, H.J. and VOSTROWSKY, O. 1982. Struktur und Vorkommen-Isoliernng und Stmkturaufkl/irung-Synthese-Biologische Aktivit/it und Verhaltensausl6sung--Anwendung im Pflanzenschutz. Naturwissenschaften 69:457-471. BOGENSCHUTZ,n . , KNAUF,W., TRI3GER, E.J., BESTMANN,H.J., and VOSTROWSKY,O. 1985. Pheromone 49: Freilandf~inge yon Geometriden-M/innchen mit C~9-Polyenen in Kiefernbest/inden. Z. Angew. Entomol. 100:349-354. BRANDSMA,L. 1971. Preparative Acetylenic Chemistry, 1st ed. Elsevier, New York. 207 pp. BROWN, C.A., and AHUJA,V.K. 1973. "P-2 nickel" catalyst with ethylenediamine, a novel system for highly stereospecific reduction of alkynes to cis-olefins. J. Chem. Soc. Chem. Commun. 1973:553-554. BROWN, H.C. 1975. Organic Synthesis via Boranes. John Wiley & Sons, New York. pp. 105-107. COREY, E.J., PYNE, S.G., and Su, W.-G. 1983. Total synthesis of leukotriene Bs. Tetrahedron Lett. 24:4883-4886. DESCOINS, C. and FRI~ROT, B. 1984. XVIIth International Symposium of Entomology, Hamburg, August 20-26, 1984. DESCOINS, C., LALANNE-CAssou,B., MALOSSE,C., and MILAT, M.-L. 1986. Analyse de la ph6romone sexuelle 6mis6 par la femelle vierge de mocis latipes (Guende) (Noctuidae, Catocalinae de Guadeloupe, Antilles Francaises). C.R. Acad. Sci. Paris 302(Serie III, 13):509-512. DUNCAN, D.B. 1955. Multiple range and multiple F tests. Biometrics 11:1-41. EBATA, T., and MORI, K. 1989. Synthesis of both the enantiomers of (Z)-cis-9,10-epoxy-6-heneicosene. Agric. Biol. Chem. 53:801-804. LITER, K., LIEB, F., DISSELNK(3TTER,H., and OEDIGER,H. 1978. Synthese hochunges/ittigter Fetts/iuren und einiger Derivative; neue C-C-Verkniipfungsmethode zum Aufgbau yon Vorstufen der biologischen Prostaglandin-Synthese. Justus Liebigs Ann. Chem. 00:658-674. GAREGG, P.J., and SAMUELSSON,B. 1980. Novel reagent system for converting a hydroxy group into an iodo group in carbonhydrates with inversion of configuration. Part 2. J. Chem. Soc. Perkin I 1980:2866-2869. GLEASON, J.G., BRYAN, D.B., and KINZIG, C.M. 1980. Convergent synthesis of leukotriene A methyl ester. Tetrahedron Lett. 21 : 1129-1132. HANSON, R.M., and SHARPLESS, K.B. 1986. Procedure for the catalytic asymmetric epoxidation of allylic alcohols in the presence of molecular sieves. J. Org. Chem. 51:1922-1925. JAIN, S.C., DUSSOURD, D.E., CONNOR, W.E., EISNER, T., GUERRERO, A., and MEINWALD, J. 1983. Polyene pheromone components from an arctiid moth (Utethesa ornatrix): Characterization and synthesis. J. Org. Chem. 48:2266-2270. KATSUKI, T., and SHARPLESS, K.B. 1980. The first practical method for asymmetric epoxidation. J. Am. Chem. Soc. 102:5974-5976. KOVALEV,B.G., and NIKOLAEVA,L.A. 1986. Attractiveness of some epoxy compounds for males of a tiger moth, Phragmatodiafuliginosa (Arctiidae), and of a geometrid moth, Caustoloma (Therapis) flavicaria (Geometridae). Zool. Zh. 65:802-804. MCDONOUGH, L.M., BAILEY,J.B., HOFFMAN,M.P., LEONHARDT,B.A., BROWN,D.F., SMITHHISLER, C.L., and OLSEN, K. 1986. Sabulodes caberata Guen6e (Lepidoptera: Geometridae). Components of its sex pheromone gland. J. Chem. Ecol. 12:2107-2116.

LEPITOPTERAN ATTRACTANTS AND PHEROMONES

929

MILLAR, J.G., and UNDERHILL,E.W. 1986. Synthesis of chiral bishomoallylic epoxides, a new class of lepidopteran sex attractants. J. Org. Chem. 51:4726-4728. MILLAR, J.G., UNDERHILL,E.W., GIBLIN,M., and BARTON, D. 1987. Sex pheromone components of three species of Semiothisa (Geometridae), (Z,Z,Z)-3-6,9-heptadecatriene and two monoepoxydiene analogs. J. Chem. Ecol. 13:1371-1383. MILLAR, J.G., GmLIN, M., BARTON, D., and UNDERHILL, E.W. 1990a. 3Z,6Z,9Z-nonadecatriene and enantiomers of 3Z,9Z-cis-6,7-epoxy-nonadecadiene as sex attractants of two geometrid and one noctuid moth species. J. Chem. Ecol. 16:215i-2166. MILLAR, J.G., GIBLIN, M., BARTON, D., and UNOERHILL, E.W. 1990b. 3Z,6Z,9Z-Trienes and unsaturated epoxides as sex attractants for geometrid moths. J. Chem. Ecol. 16:2307-2316. MILLAR, J.G., GIBLIN, M., BARTON, D., MORRISON,A., and UNDERHILLE.W. 1990c. Synthesis and field testing of enantiomers of 6Z,9Z-cis-3,4-epoxydienes as sex attractants for geometrid moths. Interactions of enantiomers and regioisomers. J. Chem. Ecol. 16:2317-2339. MILLAR, J.G., GIBLIN, M., BARTON, D., REYNARD, D.A., NEILL, G.B., and UNDERHILL, E.W. 1990d. Identification and field testing of female-produced sex pheromone components of the spring cankerworm, Paleacrita vernata Peck (Lepidoptera: Geometridae). J. Chem. Ecol. 1~6:3393-3409. MILLAR, J.G., GmLIN, M., BARTON, D., and UNDERmLL, E.W. 1991a. Chiral lepidopteran sex attractants: Blends of optically active C20 and C2~ diene epoxides as sex attractants for geometrid and noctuid moths. Environ. Entomol. In press. MILLS, L.S., and NORTH, P.C. 1983. A short syhnthesis of a leukotriene B4 synthon. Tetrahedron Lett. 24:409-410. MORI, K., and EBATA,T. 1981. Synthesis of optically active pheromones with an epoxy ring. (+)disparlure and the saltmarsh caterpillar moth pheromone, [(Z,Z)-3,6-cis-9,10-epoxyheneicosadiene]. Tetrahedron Lett. 22:4281-4282. MORI, K., and EBATA,T. 1986. Synthesis of optically active pheromones with an epoxy ring, (+)disparlure and both the enantiomers of (3Z,6Z)-cis-9,10-epoxy-3,6-heneicosadiene. Tetrahedron 42;3471-3478. NICOLAOtl, K.C., and WEBBER, S.E. 1985. A general strategy for the synthesis of the presumed lipoxin structures. J. Chem. Soc. Chem. Commun. 1985:297-298. NICOLAOU, K.C., DUGGAN,M.E., and LADDUWAHErTY,T. 1984. Reactions of 2,3-epoxyhalides. Synthesis of optically active allylic alcohols and homoallylic epoxides. Tetrahedron Lett. 25:2069-2072. OSBOND, J.M. 1961. Essential fatty acids. Part II. Synthesis of (+)-vemolic, linoleic, and ~,linolenic acid. J. Chem. Soc. 1961:5270-5275. ROLLtN, P., and POUGNY,J.-R. 1986. Synthesis of 6Z-cis-9S, 10R-epoxyheneicosene, a component of the ruby tiger moth pheromone. Tetrahedron 42:3479-3490. SOKAL, R.R., and ROnLF, F.J. 1981. Biometry, 2nd ed. W.H. Freeman, New York. SzOcs, G., TOTH, M, BESTMANN,H.J., and VOSTROWSKY,O. 1984. A two-component sex attractant for males of the geometrid moth Alsophilia quadripunctata. Entomol. Exp. Appl. 36:287291. SLESSOR,K.N., KING, G.G.S., MmLER,D.R., WINSTON,M.L., and CUTFORTH,T.L. t985. Determination of chirality of alcohol or latent alcohol semiochemicals in individual insects. J. Chem. Ecol. 11:1659-1667. UNDERHILL, E.W., PALANISWAMY,P., ABRAMS,S.R., BAILEY,B.K., STECK,W.F., and CHISHOLM, M.D. 1983. Triunsaturated hydrocarbons, sex pheromone components of Caenurgina erechtea. J. Chem. Ecol. 9:1413-1423. WONG, J.W., UNDERHILL,E.W., MACKENZIE,S.L., and CHISHOLM, M.D. 1985. Field trapping and electroantennographic responses to triene hydrocarbons and monoepoxydiene derivatives. J. Chem. Ecol. I 1:727-756.