Natural and unnatural terpenoid precursors of insect juvenile hormone

Article abstract of DOI:10.1021/jo962008q

The biosynthesis of insect juvenile hormone (JH) is due, in part, to the precise head-to-tail coupling of allylic and homoallylic diphosphate substrates, as catalyzed by one or more prenyltransferases. To better understand this enzyme's role in JH production, homodimethylallyl diphosphate and both the natural and unnatural homologs of geranyl diphosphate have been prepared as potential substrates for insect prenyltransferase. These latter materials were constructed in a convergent manner by olefination of the corresponding trisnoraldehydes obtained from either terminal oxidative cleavage of geraniol or higher-order cuprate conjugate addition to acrolein. To aid in characterizing the nature of the terpenoid skeletons formed from our in vitro studies, homologous derivatives of farnesol were also prepared by anion coupling of the geranyl derivatives to either C₅ or C₆ allylic bromides. The preparation of these materials and the results of incubations with larval corpora allata homogenates of the lepidopteran Manduca sexta are described.

Full text of DOI:10.1021/jo962008q

J . Org. Chem. 1997, 62, 3529-3536
3529
Na tu r a l a n d Un n a tu r a l Ter p en oid P r ecu r sor s of In sect J u ven ile
Hor m on e
Stephanie E. Sen* and Gregory J . Ewing
Department of Chemistry, Indiana UniversitysPurdue University at Indianapolis (IUPUI),
402 North Blackford Street, Indianapolis Indiana 46202
Received October 28, 1996X
The biosynthesis of insect juvenile hormone (J H) is due, in part, to the precise head-to-tail coupling
of allylic and homoallylic diphosphate substrates, as catalyzed by one or more prenyltransferases.
To better understand this enzyme’s role in J H production, homodimethylallyl diphosphate and
both the natural and unnatural homologs of geranyl diphosphate have been prepared as potential
substrates for insect prenyltransferase. These latter materials were constructed in a convergent
manner by olefination of the corresponding trisnoraldehydes obtained from either terminal oxidative
cleavage of geraniol or higher-order cuprate conjugate addition to acrolein. To aid in characterizing
the nature of the terpenoid skeletons formed from our in vitro studies, homologous derivatives of
farnesol were also prepared by anion coupling of the geranyl derivatives to either C5 or C6 allylic
bromides. The preparation of these materials and the results of incubations with larval corpora
allata homogenates of the lepidopteran Manduca sexta are described.
In tr od u ction
We are currently studying the activity of insect pre-
nyltransferase, a key enzyme in the biosynthesis of insect
juvenile hormone (J H).1 J H III, the most commonly-
occurring J H structure, is derived from farnesyl diphos-
phate which is obtained from the coupling of two mol-
ecules of isopentenyl diphosphate (IPP) with dimethylallyl
diphosphate (DMAPP).2 Interestingly, lepidopteran in-
sects produce a complex mixture of J H structures; for
F igu r e 1. Lepidopteran juvenile hormone (J H) structures.
example, in the tobacco hornworm, Manduca sexta, J H
has been identified as five different epoxy-farnesoate
homologs (J H 0-J H III, and methyl J H I, Figure 1).3
Despite considerable research in the area of J H biosyn-
thesis,4 the factors which control J H homolog formation
have yet to be fully elucidated. Because of the potential
utility of agents which disrupt J H biosynthesis as
insecticides and because of the pivotal role that prenyl-
transferase plays in the construction of the J H carbon
skeletons, we felt that a systematic study of the substrate
specificity of lepidopteran prenyltransferase would be
useful in determining whether this enzyme could serve
as a new target for anti-juvenoid development.5 To
perform these experiments, we required homodimethy-
lallyl diphosphate (HDMAPP, 1b) and all possible ho-
mologs of the intermediate geranyl diphosphate (GPP,
compounds 2a -d , Figure 2). Herein, we report on the
preparation of these compounds, as well as the synthesis
F igu r e 2. Allylic diphosphate precursors to natural and
unnatural insect J H and corresponding farnesol derivatives.
X Abstract published in Advance ACS Abstracts, April 15, 1997.
(1) (a) Sen, S. E.; Ewing, G. J .; Childress, M. J . Agric. Food Chem.
1996, 44, 472. (b) Sen, S. E.; Ewing, G. J .; Thursten, N. Arch. Insect
Biochem. Physiol. 1996, 32, 315.
(2) Poulter, C. D.; Rilling, H. C. In Biosynthesis of Isoprenoid
Compounds; Porter, J . W., Spurgeon, S. L., Eds.; Wiley: New York,
1983; Vol. 1, p 161.
(3) (a) Baker, F. C. In Morphogenic Hormones of Arthropods; Gupta,
A. P., Ed.; Rutgers University Press: New Brunswick, 1990; Vol. 1, p
389. (b) Schooley, D. A.; Baker, F. C.; Tsai, L. W.; Miller, C. A.
J amieson, G. C. In Biosynthesis Metabolism and Mode of Action of
Invertebrate Hormones; Hoffmann, J ., Porchet, M., Eds.; Springer-
Verlag: Berlin; 1984; p 373.
(4) (a) Law, J . H. In Biosynthesis of Isoprenoid Compounds; Porter,
J . W., Spurgeon, S. L., Eds.; Wiley: New York, 1983; Vol. 2, p 507. (b)
Schooley, D. A.; Baker, F. C. In Comprehensive Insect Physiology,
Biochemistry, and Pharmacology; Kerkut, G. A., Gilbert, L. I., Eds.,
Pergamon Press: Oxford, 1985; Vol. 7, p 363.
of the corresponding farnesol homologs which serve as
authentic analytical samples for our in vitro assays (3a -
h , Figure 2). Although many natural and unnatural J H
carbon skeletons have been constructed by others,6 we
were interested in developing a shorter, higher-yielding,
convergent synthetic scheme which would allow the
preparation of a variety of homologous terpenoid struc-
tures for future structure-activity relationship and
inhibitor studies.
Resu lts a n d Discu ssion
Syn th esis of GP P Hom ologs a n d HDMAP P .
A
(5) Henrick, C. A. In Proc. Conf. Insect Chem. Ecol.; Hrdy´, I., Ed.;
SPB Academic Publishing: The Hague, 1991; p 429.
retrosynthetic analysis of the geraniol homologs sug-
S0022-3263(96)02008-7 CCC: $14.00 © 1997 American Chemical Society

3530 J . Org. Chem., Vol. 62, No. 11, 1997
Sen and Ewing
Sch em e 1. Syn th esis of Un n a tu r a l Ger a n iol
Hom olog 9ca
Sch em e 2. Attem p ted Syn th etic Rou te for th e
Con str u ction of Ger a n iol Hom ologs 9a ,ba
a
(a) (Bu3Sn)2CuLi, THF, -78 °C (80%); (b) DIBALH, THF, -40
to 0 °C (82%); (c) t-BuPh2SiCl, DMAP, Et3N, CH2Cl2 (91%); (d) (1)
n-BuLi, THF, -40 °C; (2) 2-ThCu(CN)Li, -25 °C; (3) acrolein,
TMSCl, -78 °C (63%); (e) i-PrPPh3Br, n-BuLi, THF, 0 °C (92%);
(f) TBAF, THF, 0 °C (quant).
gested that the ∆-6,7 olefin could be constructed from the
corresponding trisnoraldehyde derivatives by either Wit-
tig or Horner-Emmons-Wadsworth olefination. The
homologous 4-ethyl aldehyde precursor (7b, Scheme 1)
could be formed from conjugate addition to acrolein of
the corresponding higher-order vinyl cuprate, generated
by vinylstannane transmetalation,7 while the truncated
derivative of geraniol (7a , Scheme 2) would be prepared
by known methodology involving the selective oxidative
cleavage of TBDPS-protected geraniol.8
Following the procedure developed by Piers and co-
workers,9 regioselective conjugate addition of bis(tri-n-
butylstannyl)lithium cuprate to ethyl 2-pentynoate pro-
duced trans-stannene 4 as the sole product (Scheme 1).
DIBALH reduction of the R, -unsaturated ester of 4
yielded the corresponding alcohol (5) which was protected
as the TBDPS ether. Vinylstannane 6 was converted into
the higher-order mixed cuprate by transmetalation (n-
BuLi, then reaction with lithium 2-thienylcyanocuprate)10
a
(a) MeCH(CO2Et)P(O)(OEt)2, KHMDS, 18-C-6, THF, -78 °C,
(80%); (b) DIBALH, THF, -40 to 0 °C (95%); (c) NCS, DMS,
CH2Cl2, -40 to 0 °C (95%); (d) MnO2, hexane, 0 °C (80%); (e)
CH2dPPh3, THF, 0 °C (95%); (f) Me(2-Th)Cu(CN)Li2, THF, -78
°C; (g) Ph3RhCl, H2, PhH, 1 atm or Cp2Zr(H)Cl, THF, 0 °C to rt.
and reacted with acrolein in the presence of TMSCl.11
Wittig olefination of the conjugate addition product,
aldehyde 7b, using isopropyltriphenylphosphorane and
subsequent alcohol deprotection with TBAF proceeded as
expected to provide 9c (six steps, 32% overall yield).
Attempts to prepare the C-7 ethyl and C-3,7 diethyl
geraniol homologs (9a and 9b, respectively) from alde-
hydes 7a and 7b by Horner-Emmons olefination are
summarized in Schemes 2 and 3. The (2Z)-R, -unsat-
urated ester 10a was first prepared by condensa-
tion of 7a with the potassium anion of triethyl 2-phospho-
nopropionate in the presence of 18-crown-6;12 however,
subsequent approaches to convert the ester functionality
into the required ethyl group were not successful (Scheme
2). Attempts to displace the halide of 12a with several
methyl cuprates led to both SN2 and SN2′ products; the
best results were achieved with Me(2-Th)Cu(CN)Li2
which yielded an 85/15 ratio of C-8 to C-6 addition
products.13 An alternative method involving methylide-
nation of aldehyde 13a to produce triene 14a , followed
by selective reduction of the terminal olefin, was also
attempted. However, both homogenous hydrogenation
(6) (a) J ewell, C. F., J r.; Brinkman, J .; Petter, R. C.; Wareing, J . R.
Tetrahedron 1994, 50, 3849. (b) Still, W. C.; McDonald, J . H., III;
Collum, D. B.; Mitra, A. Tetrahedron Lett. 1979, 20, 593. (c) Ortiz de
Montellano, P. R.; Wei, J . S.; Castillo, R.; Hsu, C. K.; Boparai, A. J .
Med. Chem. 1977, 20, 243. (d) Chuit, C.; Cahiez, G.; Normant, J .;
Villieras, J . Tetrahedron 1976, 32, 1675. (e) Stotter, P. L.; Hornish, R.
E. J . Am. Chem. Soc. 1973, 95, 4444. (f) Henrick, C. A.; Schaub, F.;
Siddall, J . B. J . Am. Chem. Soc. 1972, 94, 5374. (g) Cochrane, J . S.;
Hanson, J . R. J . Chem. Soc., Perkins Trans. 1 1972, 361. (h) Corey, E.
J .; Yamamoto, H. J . Am. Chem. Soc. 1970, 92, 6636. (i) Corey, E. J .;
Yamamoto, H. J . Am. Chem. Soc. 1970, 92, 6637. (j) Anderson, R. J .;
Henrick, C. A.; Siddall, J . B. J . Am. Chem. Soc. 1970, 92, 735. (k)
Siddall, J . B.; Biskup, M.; Fried, J . H. J . Am. Chem. Soc. 1969, 91,
1853. (l) Mori, K.; Stalla-Bourdillon, B.; Ohki, M.; Matsui, M;
Bowers, W. S. Tetrahedron 1969, 25, 1667. (m) J ohnson, W. S.; Li,
T.-t.; Faulkner, D. J .; Campbell, S. F. J . Am. Chem. Soc. 1968, 90,
6625. (n) Corey, E. J .; Katzenellenbogen, J . A.; Gilman, N. W.; Roman,
S. A.; Erickson, B.W. J . Am. Chem. Soc. 1968, 90, 5618. (o) Dahm, K.
H.; Trost, B. M.; Ro¨ller, H. J . Am. Chem. Soc. 1967, 89, 5292.
(7) Dodd, D. S.; Pierce, H. D., J r.; Oehlschlager, A. C. J . Org. Chem.
1992, 57, 5250.
(8) Davisson, V. J .; Neal, T. R.; Poulter, C. D. J . Am. Chem. Soc.
1993, 115, 1235.
(9) Piers, E.; Chong, J . M.; Morton, H. E. Tetrahedron 1989, 45, 363.
(10) (a) Behling, J . R.; Babiak, K. A.; Ng, J . S.; Campbell, A. L.;
Moretti, R.; Koerner, M.; Lipshutz, B. H. J . Am. Chem. Soc. 1988,
110, 2641. (b) Lipshutz, B. H. Synthesis 1987, 325.
(11) Matsuzawa, S.; Horiguchi, Y.; Nakamura, E.; Kuwajima, I.
Tetrahedron 1989, 45, 349.
(12) Still, W. C.; Gennari, C. Tetrahedron Lett. 1983, 24, 4405.
(13) Lipshutz, B. H.; Sengupta, S. Org. React. 1992, 41, 135.

Terpenoid Precursors of Insect J uvenile Hormone
J . Org. Chem., Vol. 62, No. 11, 1997 3531
Sch em e 3. Syn th esis of Ger a n iol Hom ologs 9a
a n d 9ba
Sch em e 4. Syn th esis of 20a ,ba
a
(a) t-BuPh2SiCl, DMAP, Et3N, CH2Cl2 (82%); (b) catalytic
a
(a) Et(CO2Me)CdPPh3, THF, rt; (b) DIBALH, THF, -40 °C
SeO2, t-BuOOH, salicylic acid, CH2Cl2 (58%); (c) (1) MsCl, Et3N,
CH2Cl2, -40 °C; (2) LiBr, THF, 0 °C (86%); (d) (1) n-BuLi, THF,
-40 °C; (2) CH3OC(O)Cl, -78 °C (74%); (e) DIBALH, THF, -40
to 0 °C.
to 0 °C; (c) (1) MsCl, Et3N, CH2Cl2, -40 °C; (2) LiCl, THF, 0 °C;
(d) LiEt3BH, THF, 0 °C; (e) TBAF, THF, 0 °C.
(Wilkinson’s catalyst) and reduction with Cp2Zr(H)Cl
yielded approximately 15% of the corresponding ∆-7,8
rearranged olefin in addition to the desired product.14,15
Because of the unsatisfactory results obtained from
transformations involving the ∆-6,7 cis olefin, a modified
synthesis was developed (Scheme 3). Wittig olefination
of either 7a or 7b with (1-carbomethoxypropylidene)-
triphenylphosphorane generated the ∆-2,3 trans olefin
as the predominant product (80% yield, 97% isomeric
purity).16 Esters 15a and 15b were then reduced with
DIBALH and converted into the allylic chlorides 17 by
in situ displacement of the corresponding mesylates with
LiCl.17 Reduction with Super-Hydride18 provided 8a and
8b in 72 and 87% yields, respectively. In contrast to the
trisubstituted cis-allylic chloride 12a , reduction of both
17a and 17b occurred regioselectively to provide alcohols
9a and 9b after silyl deprotection.
The alcohol of HDMAPP was synthesized by known
methodology.6k,19 Initially, methylation of the anion of
vinylstannene 6 was attempted; however, this approach
led to a significant amount of protonated byproduct which
could not be easily separated from the desired material.9
Once prepared, geraniol homologs 9a -9c and homodim-
ethylallyl alcohol were converted into diphosphates by
displacement of the corresponding allylic chlorides with
tris(tetra-n-butylammonium) diphosphate.20
or 20b, Scheme 4). Bromide 20a was synthesized from
TBDPS-protected dimethylallyl alcohol by SeO2 allylic
oxidation and subsequent bromination of the resulting
hydroxyl moiety.21 Compound 20b was synthesized by
the reaction of the vinyl anion of 6 with methyl chloro-
formate, followed by DIBALH reduction and allylic
bromination.22
Using the procedure first developed by Yamamoto and
co-workers,22,23 the coupling of the geranyl derivatives
23a -d (obtained from alcohols 9a -d , by conversion to
the mesylate followed by in situ treatment with LiCl) to
allylic bromides 20a and 20b was performed (Scheme 5).
Unfortunately, the reaction suffered from significant
Wurtz and -addition coupling. To minimize the amount
of dimerization, the allylic anion was generated at a low
concentration (20 mM) by dropwise (>10 min) addition
of an allylic chloride solution to a rapidly stirring Rieke
barium metal suspension at -78 °C. Similar alterations
have been successfully applied to the generation of
Grignard reagents24 and, in the case of allylic barium
anion formation, reduced the amount of Wurtz coupling
to less than 10%. Despite these modifications, the
reaction produced a mixture of heterocoupling products,
including the desired one (i.e., 24a -h , 70-75% by GC)
and the -addition isomer (25a -h , 20-25%).
Syn th esis of F a r n esyl Hom ologs. A retrosynthetic
analysis of farnesol homologs 3b-h suggested that these
materials could be obtained from the corresponding
geraniol homologs by coupling of the homogeranylbarium
anions to either C5 or C6 allylic bromide derivatives (20a
Because of the inconvenience in obtaining isomerically
pure farnesol homologs by the above synthetic method,
attempts were made to find a different approach to the
barium coupling reaction. Since allylic transposition with
barium anions is greatly diminished when aldehydes are
used as the electrophile,23a we attempted to utilize
aldehyde 26 in place of allylic bromides 20a ,b (Scheme
6). As expected, the desired R-coupling occurred in >95%;
however, subsequent removal of the secondary allylic
alcohol functionality from 27 proved difficult. Several
(14) Candlin, J . P.; Oldham, A. R. Discuss. Faraday Soc. 1968, 46,
60.
(15) Schwartz, J .; Labinger, J . A. Angew. Chem., Int. Ed. Engl. 1976,
15, 333.
(16) (a) Marshall, J . A.; DeHoff, B. S.; Cleary, D. G. J . Org. Chem.
1986, 51, 1735. ( b) Bestmann, H. J . Angew. Chem., Int. Ed. Engl. 1965,
4, 645.
(17) (a) McMurry, J . E.; Erion, M. D. J . Am. Chem. Soc. 1985, 107,
2712. (b) Collington, E. W.; Meyers, A. I. J . Org. Chem. 1971, 36, 3044.
(18) (a) Coates, R. M.; Denissen, J . F.; Croteau, R. B.; Wheeler, C.
J . J . Am. Chem. Soc. 1987, 109, 4399. (b) Krishnamurthy, S.; Brown,
H. C. J . Org. Chem. 1983, 48, 3085.
(19) Corey, E. J .; Katzenellenbogen, J . A. J . Am. Chem. Soc. 1969,
91, 1851.
(20) (a) Davisson, V. J .; Woodside, A. B.; Neal, T. R.; Stremler, K.
E.; Muehlbacher, M.; Poulter, C. D. J . Org. Chem. 1986, 51, 4768. (b)
Davisson, V. J .; Woodside, A. B.; Poulter, C. D. Methods Enzymol. 1985,
110, 130.
(21) (a) Stephenson, L. M.; Speth, D. R. J . Org. Chem. 1979, 44,
4683. (b) Umbreit, M. A.; Sharpless, K. B. J . Am. Chem. Soc. 1977,
99, 5526. (c) Bhalerao, U. T.; Rapoport, H. J . Am. Chem. Soc. 1971,
93, 4835.
(22) Zheng, Y. F.; Oehlschlager, A. C.; Georgopapadakou, N. H.;
Hartman, P. G.; Scheliga, P. J . Am. Chem. Soc. 1995, 117, 670.
(23) (a) Yanagisawa, A.; Habaue, S.; Yamamoto, H. J . Am. Chem.
Soc. 1991, 113, 8955. (b) Corey, E. J .; Shieh, W.-C. Tetrahedron Lett.
1992, 33, 6435.
(24) Oppolzer, W.; Ku¨ndig, E. P.; Bishop, P. M.; Perret, C. Tetra-
hedron Lett. 1982, 23, 3901.

3532 J . Org. Chem., Vol. 62, No. 11, 1997
Sen and Ewing
Ta ble 1. Cou p lin g Efficien cy of Hom ologou s Allylic Dip h osp h a te P r ecu r sor s for P r en yltr a n sfer a se of La r va l
Lep id op ter a n In sect, M. sexta
prenyltransferase activity
larval M. sexta corpora allataa
relative prenyltransferase activity
% GPP
or homologue
formed
% FPP
or homologue
formed
prenyltransferase
larval M. sexta
corpora allata
FPP
FPP
FPP
allylic
substrate
synthase
synthase I
synthase II
pig liverb
Bombyx morib
B. morib
1a (DMAPP)
5
9
1.5
3
1
1
1
1
1b
2
0.4
0.5
0.76
ndc
1
0.04
0.38
0.38
nd
0.07
0.53
0.57
nd
2a
14.9
11.4
4.2
1.28
0.98
0.36
1
2b
2c
2d (GPP)
11.6
1
1
a
b
Results from this study; see text for experimental details. From ref 27b. c Not determined.
Sch em e 5. Allyl Ba r iu m Cou p lin g of Allylic
Sch em e 6. Attem p ted Syn th esis of 3a -h Usin g
Ch lor id es 23a -d w ith Br om id es 20a a n d 20ba
Ca r bon yl Electr op h iles
a
(a) 1) Ba, THF, -78 °C; (2) 20a or 20b, -78 °C; (b) (1) TBAF,
THF, 0 °C; (2) HPLC purification.
purified FPP synthase from vertebrate or whole body
insect sources,27 the larval enzyme obtained from M. sexta
corpora allata (the site of hormone production) shows a
high tolerance for the homologous substrates, in accord
with the insect’s ability to prepare J H homolog struc-
tures. HDMAPP was a better substrate than DMAPP,
and geranyl homologs 2a and 2b were converted into the
corresponding farnesyl homolog skeletons with compa-
rable efficiency to GPP. Interestingly, the unnatural
geranyl homolog 2c was a poorer substrate of the larval
prenyltransferase, suggesting that this enzyme is at least
in part the source of J H skeleton specificity in the
lepidopteran insects. A more comprehensive study of the
substrate selectivity of prenyltransferase in both lepi-
dopteran and non-lepidopteran insects is currently under
investigation in our laboratory.
methods (PBr3, Ph3P/CBr4, MsCl/LiBr, and NBS/DMS)
utilized to convert 27 into the C-4 halide 28 were
unsuccessful, producing an inseparable mixture of C-2-
and C-4-halogenated products (30-40% undesired iso-
mer).25 Attempts to reduce the corresponding C-4 me-
sylate in situ with both Super-Hydride and N-Selectride
were also problematic as both hydride reagents gave SN2
and SN2′ addition products.26 This latter result was
surprising since it would seem that the TBDPS ether
should provide enough steric hindrance to preclude
attack at the C-2 position by the bulky hydride reagents.
An umpolung approach to the barium coupling method
(i.e., coupling of 30 with 31, Scheme 6) was also at-
tempted; however, this too failed because of competing
elimination of the silyl ether of 30. Thus, farnesol
homologs 3b-h were best prepared by the original allylic
barium coupling method, and the desired isomer was
purified by reversed phase HPLC separation of the
deprotected terpenols to give typical isolated yields of 30-
40%.
Exp er im en ta l Section
Gen er a l P r oced u r es. Syn th etic Meth od s. Unless oth-
erwise stated, chemicals obtained from commercial sources
In Vitr o Stu d ies. Using each of the prepared allylic
diphosphates and the farnesol homolog standards, an
examination of substrate specificity for larval prenyl-
transferase of M. sexta was performed (Table 1). Unlike
(27) (a) Koyama, T.; Matsubara, M.; Ogura, K. J . Biochem. 1985,
98, 449. (b) Koyama, T.; Matsubara, M.; Ogura, K. J . Biochem. 1985,
98, 457. (c) Koyama, T.; Ogura, K.; Seto, S. J . Chem. Soc. J pn. 1981,
5, 689. (d) Koyama, T.; Saito, A.; Ogura, K.; Seto, S. J . Am. Chem.
Soc. 1980, 102, 3614. (e) Shinka, T.; Ogura, K.; Seto, S. J . Biochem.
1975, 78, 1177. (f) Nishino, T.; Ogura, K.; Seto, S. Biochim. Biophys.
Acta 1973, 302, 33. (g) Nishino, T.; Ogura, K.; Seto, S. J . Am. Chem.
Soc. 1972, 94, 6849. (h) Ogura, K.; Koyama, T.; Seto, S. J . Chem. Soc.,
Chem. Commun. 1972, 881. (i) Ogura, K.; Nishino, T.; Koyama, T.;
Seto, S. J . Am. Chem. Soc. 1970, 92, 6036. (j) Popja´k, G.; Rabinowitz,
J . L.; Baron, J . M. Biochem. J . 1969, 113, 861.
(25) Magid, R. M. Tetrahedron 1980, 36, 1901.
(26) (a) Krishnamurthy, S.; Brown, H. C. J . Org. Chem. 1976, 41,
3064. (b) Parry, R. J .; Kunitani, M. G. J . Am. Chem. Soc. 1976, 98,
4024. (c) Bhalerao, U. T.; Plattner, J . J .; Rapoport, H. J . Am. Chem.
Soc. 1970, 92, 3429.

Terpenoid Precursors of Insect J uvenile Hormone
J . Org. Chem., Vol. 62, No. 11, 1997 3533
3
were used without further purification. THF was distilled
from sodium benzophenone ketyl, C6H6, CH2Cl2, CH3CN, and
methyl chloroformate were distilled from CaH2, and Et3N was
distilled from KOH. Acrolein was freshly distilled before use.
NCS and Wittig salts were recrystallized (from H2O and CH2-
Cl2/hexane, respectively) and dried in vacuo at 60 °C. Stan-
dard workup refers to a brine wash of the combined organic
extracts, followed by drying over MgSO4 and rotary evapora-
tion. Unless otherwise indicated, chromatography refers to
flash chromatography using silica gel 60 (EM Science). Ion-
exchange chromatography was performed on Dowex 50WX8-
9.5 Hz), 5.69 (t, 1H, J ) 6.2 Hz, J Sn-H ) 68.3 Hz); 13C NMR
9.7, 13.7, 15.1, 26.5, 27.4, 29.1, 58.8, 138.5, 149.9.
(E)-3-(Tr ibu tylstan n yl)-1-((ter t-bu tyldiph en ylsilyl)oxy)-
2-p en ten e (6). To a solution of 5 (3.4 g, 9 mmol) in CH2Cl2
(75 mL) were added Et3N (1.45 mL, 10.4 mmol), tert-butyl-
chlorodiphenylsilane (2.6 g, 9.5 mmol), and a catalytic amount
of DMAP (50 mg, 0.4 mmol). After the solution was stirred
for 2 h at rt, H2O (50 mL) was added, and the reaction mixture
was extracted with Et2O (3 × 50 mL). The combined organics
were subjected to the standard workup and chromatographed
using EtOAc/hexane (5/95) as eluent to provide 6 (5.0 g, 8.2
mmol, 91%): GC 30.3 min; IR (neat) cm-1 3072, 3051, 2958,
+
200 (NH4 or H+ form) which was prepared by treating the
resin with a 3-4 N solution of the desired ion (HCl for H+
1
2929, 2871, 2857, 1584, 1112, 823; H NMR 0.82-0.95 (m,
+
and NH4OH for NH4 forms) for 1 h at a flow rate of 1 mL/
18H), 1.08 (s, 9H), 1.35 (sextet, 6H, J ) 6.5 Hz), 1.47-1.56
3
min. Cellulose chromatography was performed using What-
man CF11 fibrous cellulose powder which was prepared by
consecutive washings with 1 N HCl and 1 N NaOH for 30 min,
followed by extensive rinsing with H2O. For monitoring
diphosphate formation, TLC was performed with MN CEL 300
fibrous cellulose TLC plates (prewashed as described for the
cellulose powder) using Hanes stain for visualization.28 Gas-
liquid chromatography (GC) was performed using a DB-5HT
30 m column with elution conditions as follows: flow rate 1.5
mL/min, initial temperature 50 °C for 1 min, increasing at 10
°C/min to a final temperature of 325 °C. 1H and 13C NMR
spectra were recorded at 300 and 75 MHz, respectively, using
CDCl3 as solvent, except for diphosphates 1b and 2a -d which
were dissolved in D2O with MeOH added as an internal
standard. 31P NMR spectra were obtained at 81 MHz, using
D2O as solvent and 30% H3PO4 as an external standard.
Preparative HPLC was performed on an 10 × 250 mm
Ultrasphere-ODS column, monitoring at 210 nm. Biologica l
Assa ys. [4-14C]Isopentenyl diphosphate was purchased from
DuPont New England Nuclear. Corpora cardiaca-corpora
allata complexes of day zero, 5th stadium larvae (V/0) were
obtained using previously established microsurgical methods.29
Eth yl (E)-3-(Tr ibu tylsta n n yl)-2-p en ten -1-oa te (4). To
a cold (-20 °C) solution of hexabutylditin (16 g, 27.6 mmol) in
THF (250 mL) was added n-BuLi (1.6 M in hexanes, 17.3 mL,
27.7 mmol). After being stirred for 20 min at -20 °C, a yellow
solution was obtained. The reaction vessel was cooled to -50
°C, and CuBr‚DMS (2.8 g, 13.6 mmol) was added in one portion.
The reaction gradually became a dark brown suspension as it
stirred at -50 °C for 30 min. Ethyl 2-pentynoate (1.9 g, 15
mmol) was then added at -78 °C, and the mixture was stirred
for 4 h. The reaction was quenched by the addition of
saturated NH4Cl/NH4OH (9/1, 100 mL) and Et2O (50 mL).
After being stirred for 30 min at rt, the solution was rinsed
with NH4Cl/NH4OH (3 × 100 mL) and extracted with Et2O (3
× 50 mL), and the combined organics were subjected to the
standard workup. Chromatography using EtOAc/hexane (0/
100 to 10/90 gradient) as the eluent provided 4 as a clear oil
(4.6 g, 11 mmol, 80%): GC 20.8 min; IR (neat) cm-1 2958, 2873,
1720, 1595, 1171, 863; 1H NMR 0.87-0.98 (m, 15H), 1.04 (t,
3H, J ) 7.5 Hz), 1.25-1.39 (m, 9H), 1.42-1.58 (m, 6H), 2.86
(m, 6H), 2.09 (q, 2H, J ) 7.4 Hz, J Sn-H ) 57.9 Hz), 4.36 (d,
3
2H, J ) 5.5 Hz, J Sn-H ) 16.5 Hz), 5.73 (t, 1H, J ) 5.5 Hz,
3J Sn-H ) 70.8 Hz), 7.41 (m, 6H), 7.71 (m, 4H); 13C NMR 9.7,
13.8, 14.9, 19.2, 26.6, 26.9, 27.5, 29.2, 60.7, 127.6, 129.6, 134.1,
135.7, 139.4, 147.1.
(E)-6-((ter t-Bu t yld ip h en ylsilyl)oxy)-4-et h yl-4-h exen -
1-a l (7b). To a solution of 6 (5.0 g, 8.2 mmol) in THF (200
mL) at -40 °C was added n-BuLi (1.6 M in hexanes, 6.1 mL,
9.8 mmol) over 5 min. After the solution was stirred for 1 h
at -40 °C, lithium 2-thienylcyanocuprate (0.25 M in THF, 40
mL, 10 mmol) was added dropwise, and the reaction was
warmed to -25 °C over 45 min to yield a clear honey-colored
solution of the higher-order mixed cuprate. The reaction was
cooled to -78 °C, and a solution of acrolein (1.7 mL, 25 mmol)
and TMSCl (6.2 mL, 49 mmol) in THF (12 mL) was added over
20 min in the dark. The mixture was stirred at -78 °C for 3
h and then quenched by the addition of 1 N HCl (200 mL).
The solution was extracted with Et2O (3 × 75 mL) and
subjected to the standard workup. Chromatography of the
resulting oil using EtOAc/hexane (5/95) as the eluent yielded
7b (2.0 g, 5.2 mmol, 63%): GC 26.0 min; IR (neat) cm-1 3071,
1
2962, 2719, 1726, 1680, 1602, 1112; H NMR 0.89 (t, 3H, J
) 7.5 Hz), 1.09 (s, 9H), 1.90 (q, 2H, J ) 7.5 Hz), 2.35 (t, 2H, J
) 7.4 Hz), 2.53 (t, 2H, J ) 7.3 Hz), 4.29 (d, 2H, J ) 6.1 Hz),
5.38 (t, 1H, J ) 6.1 Hz), 7.40-7.45 (m, 6H), 7.72-7.75 (m, 4H),
9.78 (br s, 1H); 13C NMR 13.2, 19.2, 23.8, 26.9, 28.3, 42.0,
60.6, 124.5, 127.7, 129.7, 133.9, 135.7, 140.9, 202.2.
(2E)-1-((ter t-Bu tyld ip h en ylsilyl)oxy)-3-eth yl-7-m eth yl-
2,6-octa d ien e (8c). n-BuLi (1.6 M in hexanes, 1.85 mL, 3.0
mmol) was added dropwise to a suspension of isopropyltriph-
enylphosphonium iodide (1.3 g, 3.0 mmol) in THF (70 mL) at
-78 °C. After 5 min the reaction was warmed to 0 °C and
stirred for 1 h. A solution of 7b (450 mg, 1.2 mmol) in THF (5
mL) was added dropwise to the resulting red ylide. After the
solution was stirred at 4 °C for 2 h, the reaction was quenched
with H2O (50 mL) and subjected to the standard workup.
Chromatography using EtOAc/hexane (5/95) as eluent yielded
8c (440 mg, 1.1 mmol, 92%): GC 26.4 min; IR (neat) cm-1 3071,
1
2931, 1665, 1586, 1112; H NMR 0.86 (t, 3H, J ) 7.6 Hz),
1.06 (s, 9H), 1.63 (s, 3H), 1.71 (s, 3H), 1.88 (q, 2H, J ) 7.5
Hz), 2.02-2.09 (br m, 4H), 4.26 (d, 2H, J ) 6.1 Hz), 5.14 (t,
1H, J ) 6.3 Hz), 5.37 (t, 1H, J ) 6.1 Hz), 7.35-7.45 (m, 6H),
7.70-7.73 (m, 4H); 13C NMR 13.2, 17.7, 19.2, 23.5, 25.7, 26.6,
26.8, 36.2, 60.8, 123.6, 124.3, 127.6, 129.5, 131.4, 134.1, 135.6,
142.9.
3
(q, 2H, J ) 7.6 Hz, J Sn-H ) 56.6 Hz), 4.15 (q, 2H, J ) 7.1 Hz),
3
5.90 (s, 1H, J Sn-H ) 65.8 Hz); 13C NMR 10.0, 13.6, 14.1,
14.3, 27.3, 28.5, 29.0, 59.6, 127.3, 164.2, 175.5.
(E)-3-(Tr ibu tylsta n n yl)-2-p en ten -1-ol (5). To a solution
of 4 (4.6 g, 11 mmol) in THF (300 mL) at -40 °C was added
DIBALH (1.0 M in hexane, 26 mL, 26 mmol) over 15 min. The
reaction was warmed to 0 °C over 2 h and was then quenched
by pouring the mixture into 2:1 H2O/Et2O (300 mL). The
aluminum oxides were dissipated by the slow addition of 1 N
HCl to pH 4 (lower pH led to tin cleavage).30 The aqueous
layer was extracted with Et2O (3 × 50 mL) and subjected to
the standard workup. Chromatography using EtOAc/hexane
(20/80) as eluent yielded 5 (3.4 g, 9 mmol, 82%): GC 19.4 min;
IR (neat) cm-1 3320, 2958, 2922, 2872, 2855, 1658, 875; 1H
NMR 0.85-0.91 (m, 15H), 0.94 (t, 3H, J ) 7.6 Hz), 1.30
(sextet, 6H, J ) 7.2 Hz), 1.42-1.52 (m, 6H), 2.27 (q, 2H, J )
(2E)-3-Eth yl-7-m eth yl-2,6-octa d ien -1-ol (9c). To 8c (440
mg, 1.1 mmol) in THF (40 mL) at 0 °C was added TBAF (1.0
M in THF, 2.5 mL, 2.5 mmol). After 1 h at 0 °C, the solution
was warmed to rt and stirred for 3 h. The reaction was
quenched by the addition 0.5 N HCl (30 mL) and extracted
with Et2O (3 × 40 mL). Following the standard workup,
chromatography using EtOAc/hexane (20/80) as eluent yielded
9c (190 mg, 1.1 mmol, quant): GC 12.3 min; IR (neat) cm-1
1
3335, 2985, 1657, 1112; H NMR 0.87 (t, 3H, J ) 6.6 Hz),
1.59 (s, 3H), 1.67 (s, 3H), 2.04-2.11 (br m, 6H), 4.14 (d, 2H, J
) 7.0 Hz), 5.10 (t, 1H, J ) 6.5 Hz), 5.36 (t, 1H, J ) 6.9 Hz);
13C NMR 13.7, 17.7, 23.5, 25.7, 26.6, 36.4, 59.1, 122.9, 124.0,
131.7, 145.6.
3
3
8.0 Hz, J Sn-H ) 57.1 Hz), 4.22 (d, 2H, J ) 6.2 Hz, J Sn-H
)
Meth yl (2E,6E)-8-((ter t-Bu tyldiph en ylsilyl)oxy)-2-eth yl-
6-m eth yl-2,6-octa d ien -1-oa te (15a ). To a suspension of
n-propyltriphenylphosphonium bromide (6.6 g, 17.1 mmol) in
benzene (25 mL) at 4 °C was added KHMDS (0.5 M in toluene,
(28) Hanes, C. S.; Isherwood, F. A. Nature 1949, 164, 1107.
(29) Bhaskaran, G.; J ones, G. J . Insect Physiol. 1980, 26, 431-440.
(30) Evans, D. A.; Black, W. C. J . Am. Chem. Soc. 1993, 115, 4497.

3534 J . Org. Chem., Vol. 62, No. 11, 1997
Sen and Ewing
34 mL, 17 mmol). The solution was stirred for 30 min and
then warmed to rt over 30 min at which time methyl chloro-
formate (650 L, 8.4 mmol) was added. The resulting yellow
suspension was filtered and the eluent concentrated to yield
the crude ylide (4.0 g, yellow oil). The oil was dissolved in
THF (25 mL), and aldehyde 7a (1.3 g, 3.5 mmol, prepared as
previously described)8 in THF (5 mL) was added dropwise. The
reaction was stirred at rt for 7 days and then quenched by
the addition of saturated aqueous NH4Cl (50 mL). The
solution was extracted with Et2O (3 × 50 mL), and the
combined organic extracts were subjected to the standard
workup. Chromatography using EtOAc/hexane (5/95) as elu-
ent yielded 15a (1.3 g, 2.9 mmol, 83%, >98% isomeric purity):
GC 28.9 min, (2Z,6E) isomer 28.5 min; IR (neat) cm-1 3071,
2932, 2857, 1712, 1585, 1111; 1H NMR 0.98-1.04 (m, 12H),
1.45 (s, 3H,), 2.08 (t, 2H, J ) 7.6 Hz), 2.23-2.35 (m, 4H), 3.72
(s, 3H), 4.22 (d, 2H, J ) 6.2 Hz), 5.40 (t, 1H, J ) 5.9 Hz), 6.69
7.69-7.72 (m, 4H); 13C NMR 12.9, 13.2, 19.2, 21.1, 23.5, 26.2,
26.9, 35.7, 50.1, 60.7, 124.1, 127.6, 129.6, 130.5, 134.1, 135.6,
137.6, 142.2.
(2E,6Z)-1-((ter t-Bu tyld ip h en ylsilyl)oxy)-3,7-d im eth yl-
2,6-n on a d ien e (8a ). To 17a (1.1 g, 2.5 mmol) in THF (75
mL) at -78 °C was added LiEt3BH (1.0 M in THF, 4 mL, 4.0
mmol) dropwise over 10 min. After the solution was warmed
to 0 °C, the reaction was stirred for 2 h and then quenched
with H2O (40 mL), followed by saturated aqueous NH4Cl (10
mL). The mixture was extracted with Et2O (2 × 20 mL), and
the combined organic extracts were subjected to the standard
workup. Chromatography using EtOAc/hexane (2/98) as elu-
ent yielded 8a (740 mg, 1.8 mmol, 72%): GC 26.5 min; IR
1
(neat) cm-1 3071, 2930, 1729, 1663, 1112; H NMR 0.98 (t,
3H, J ) 7.6 Hz), 1.06 (s, 9H), 1.45 (s, 3H), 1.69 (s, 3H), 1.97-
2.12 (br m, 6H), 4.24 (d, 2H, J ) 6.2 Hz), 5.09 (t, 1H, J ) 6.5
Hz), 5.40 (t, 1H, J ) 5.9 Hz), 7.37-7.46 (m, 6H), 7.70-7.72
(m, 4H); 13C NMR 12.6, 16.2, 19.1, 22.6, 24.7, 26.0, 26.8, 39.7,
61.1, 123.7, 124.2, 127.4, 129.3, 134.3, 135.6, 137.0, 137.1.
(2E,6Z)-1-((ter t-Bu tyldiph en ylsilyl)oxy)-3-eth yl-7-m eth -
yl-2,6-n on a d ien e (8b). Chloride 17b (1.35 g, 3.0 mmol) was
reacted with LiEt3BH using the procedure described for the
preparation of 8a . Compound 8b was obtained (1.1 g, 2.6
(t, 1H, J ) 7.3 Hz), 7.34-7.45 (m, 6H), 7.67-7.70 (m, 4H); 13
C
NMR 13.9, 16.3, 19.1, 20.1, 26.6, 26.8, 38.3, 51.5, 61.0, 124.8,
127.5, 129.5, 131.3, 133.9, 135.6, 135.9, 141.5, 171.2.
Meth yl (2E,6E)-8-((ter t-Bu tyld ip h en ylsilyl)oxy)-2,6-d i-
eth yl-2,6-octa d ien -1-oa te (15b). Aldehyde 7b (1.8 g, 4.7
mmol) was olefinated using the procedure described for the
preparation of 15a . Ester 15b was obtained (1.7 g, 3.6 mmol,
77%, >98% isomeric purity): GC 29.1 min, (2Z,6E) isomer 28.7
min; IR (neat) cm-1 3037, 2953, 2852, 1705, 1652, 1105; 1H
NMR 0.86 (t, 3H, J ) 7.5 Hz), 1.00-1.05 (m, 12H), 1.86 (q,
2H, J ) 7.6 Hz), 2.11 (t, 2H, J ) 7.6 Hz), 2.24-2.37 (m, 4H),
3.73 (s, 3H), 4.25 (d, 2H, J ) 6.2 Hz), 5.37 (t, 1H, J ) 6.1 Hz),
6.72 (t, 1H, J ) 7.2 Hz), 7.35-7.43 (m, 6H), 7.69-7.71 (m, 4H);
13C NMR 13.1, 13.9, 19.1, 20.1, 23.5, 26.8, 35.1, 51.5, 60.6,
124.3, 127.6, 129.5, 133.9, 134.0, 135.6, 141.6, 141.7, 168.2.
(2E,6E)-8-((ter t-Bu tyldiph en ylsilyl)oxy)-2-eth yl-6-m eth -
yl-2,6-octa d ien -1-ol (16a ). Ester 15a (1.3 g, 2.9 mmol) was
reacted with DIBALH using the procedure described for the
preparation of 5. Alcohol 16a was obtained (1.15 g, 2.7 mmol,
94%): GC 28.7 min; IR (neat) cm-1 3384, 2999, 2932, 1669,
1589, 1059; 1H NMR 1.02 (t, 3H, J ) 7.65 Hz), 1.06 (s, 9H),
1.46 (s, 3H), 2.00-2.19 (m, 6H), 4.05 (s, 2H), 4.24 (d, 2H, J )
6.1 Hz), 5.35-5.42 (m, 2H), 7.36-7.46 (m, 6H), 7.69-7.73 (m,
4H); 13C NMR 13.3, 16.3, 19.2, 21.1, 25.6, 26.9, 39.4, 61.1,
66.8, 124.3, 125.7, 127.6, 129.5, 134.0, 135.6, 136.6, 140.9.
(2E,6E)-8-((ter t-Bu tyld ip h en ylsilyl)oxy)-2,6-d ieth yl-2,6-
octa d ien -1-ol (16b). Ester 15b (1.65 g, 3.6 mmol) was reacted
with DIBALH using the procedure described for the prepara-
tion of 5. Alcohol 16b was obtained (1.35 g, 3.1 mmol, 87%):
GC 29.0 min; IR (neat) cm-1 3328, 3071, 2931, 1658, 1587,
1112; 1H NMR 0.85 (t, 3H, J ) 7.6 Hz), 0.96-1.05 (m, 12H),
1.87 (q, 2H, J ) 7.6 Hz), 2.02-2.16 (m, 6H), 4.04 (br s, 2H),
4.24 (d, 2H, J ) 6.2 Hz), 5.33-5.40 (m, 2H), 7.26-7.45 (m,
6H), 7.69-7.71 (m, 4H); 13C NMR 13.2, 13.3, 19.1, 21.1, 23.5,
25.8, 26.8, 36.1, 60.7, 66.8, 123.8, 125.9, 127.5, 129.5, 134.0,
135.6, 140.8, 142.5.
(2E,6E)-1-((ter t-Bu t yld ip h en ylsilyl)oxy)-7-(ch lor om e-
th yl)-3-m eth yl-2,6-n on a d ien e (17a ). To a solution of 16a
(1.15 g, 2.7 mmol) in CH2Cl2 (30 mL) at -40 °C were added
Et3N (520 L, 3.7 mmol) and MsCl (240 L, 3.1 mmol). After
the solution had stirred at -40 °C for 1 h, THF (20 mL) and
LiCl (290 mg, 6.8 mmol) were added and the reaction mixture
was stirred at 0 °C for 2 h. The reaction was poured into
pentane (60 mL), washed with H2O (8 × 15 mL), and subjected
to the standard workup. Chloride 17a was obtained (1.1 g,
2.5 mmol, 92%): 1H NMR 1.00-1.05 (m, 12H), 1.45 (s, 3H),
2.00-2.25 (m, 6H), 4.05 (s, 2H), 4.23 (d, 2H, J ) 6.2 Hz), 5.39
(t, 1H, J ) 6.0 Hz), 5.48 (t, 1H, J ) 7.0 Hz), 7.26-7.46 (m,
6H), 7.69-7.72 (m, 4H); 13C NMR 12.9, 16.3, 19.2, 21.0, 26.0,
26.9, 39.0, 50.1, 61.1, 124.6, 127.6, 129.6, 130.4, 134.0, 135.6,
136.3, 137.6.
mmol, 87%): GC 26.7 min; IR (neat) cm-1
3070, 2964, 1676;
1H NMR 0.85 (t, 3H, J ) 7.4 Hz), 0.98 (t, 3H, J ) 7.4 Hz),
1.06 (s, 9H), 1.69 (s, 3H), 1.87 (q, 2H, J ) 7.4 Hz), 1.98-2.08
(m, 6H), 4.25 (d, 2H, J ) 5.9 Hz), 5.10 (t, 1H, J ) 5.9 Hz),
5.36 (t, 1H, J ) 5.9 Hz), 7.35-7.43 (m, 6H), 7.69-7.72 (m, 4H);
13C NMR 12.9, 13.1, 19.2, 22.8, 23.6, 24.8, 26.1, 26.9, 36.6,
60.8, 123.6, 123.9, 127.7, 129.5, 134.5, 135.7, 137.3, 142.9.
(2E,6Z)-3,7-Dim eth yl-2,6-n on a d ien -1-ol (9a ). Ether 8a
(700 mg, 1.7 mmol) was deprotected with TBAF using the
procedure described for the preparation of 9c. Alcohol 9a was
obtained (240 mg, 1.4 mmol, 82%): GC 12.5 min; IR (neat)
1
cm-1 3332, 2961, 1665; H NMR 0.95 (t, 3H), 1.66 (s, 6H),
1.99-2.10 (m, 6H), 4.13 (d, 2H, J ) 6.9 Hz), 5.05 (t, 1H, J )
6.5 Hz), 5.40 (t, 1H, J ) 6.9 Hz); 13C NMR 12.7, 16.2, 22.8,
24.7, 26.0, 39.8, 59.3, 123.3, 123.4, 137.5, 139.6.
(2E,6Z)-3-Eth yl-7-m eth yl-2,6-n on a d ien -1-ol (9b). Ether
8b (1.1 g, 2.6 mmol) was deprotected with TBAF using the
procedure described for the preparation of 9c. Alcohol 9b was
obtained (430 mg, 2.4 mmol, 92%): GC 13.1 min; IR (neat)
cm-1 3316, 2966, 1658; 1H NMR 0.97 (2 overlapping t, 6H, J
) 6.9 Hz), 1.67 (s, 3H), 1.98-2.12 (m, 8H), 4.16 (d, 2H, J )
7.3 Hz), 5.08 (t, 1H, J ) 5.9 Hz), 5.37 (t, 1H, J ) 7.0 Hz); 13C
NMR 14.4, 15.2, 24.4, 25.1, 26.4, 27.8, 38.3, 60.7, 124.5, 125.2,
139.1, 147.3.
Eth yl (Z)-3-Meth yl-2-p en ten -1-oa te. To a suspension of
CuBr‚DMS (900 mg, 4.4 mmol) in THF (25 mL) at -40 °C was
added MeLi (1.4 M in Et2O, 6.2 mL, 8.7 mmol). After being
stirred for 40 min at -40 °C, the clear yellow solution was
cooled to -78 °C, and ethyl 2-pentyn-1-oate (500 mg, 4.0 mmol)
was added over 15 min. The reaction was stirred for 90 min
at -78 °C and then quenched by the slow addition of MeOH
(1.5 mL), followed by NH4
Cl/NH4OH (9/1, 5 mL). The solution
was warmed to rt and the organic layer separated and rinsed
with NH4
Cl/NH4OH (2 × 5 mL). Standard workup yielded
ethyl (Z)-3-methyl-2-penten-1-oate (550 mg, 3.9 mmol 98%):
GC 8.8 min; IR (neat) cm-1
2961, 2925, 2856, 1717, 1652, 1212,
1149; 1H NMR 1.04 (t, 3H, J ) 7.5 Hz), 1.23 (t, 3H, J ) 7.3
Hz), 1.85 (s, 3H), 2.59 (q, 2H, J ) 7.5 Hz), 4.10 (q, 2H, J ) 7.1
Hz), 5.59 (s, 1H); 13
C NMR 12.49, 14.27, 24.57, 26.48, 59.36,
115.46, 161.96, 166.30.
(Z)-3-Meth yl-2-p en ten -1-ol. Ethyl (Z)-3-methyl-2-penten-
1-oate (550 mg, 3.9 mmol) was reacted with DIBALH using
the procedure described for the preparation of 5. Alcohol was
obtained (230 mg, 2.3 mmol, 59%): GC 5.9 min; IR (neat) cm-1
3333, 2936, 1678; 1H NMR 0.97 (t, 3H, J ) 7.6 Hz), 1.72 (s,
3H), 2.66 (q, 2H, J ) 7.6 Hz), 4.11 (d, 2H, J ) 7.0 Hz), 5.35 (t,
1H, J ) 6.9 Hz); 13C NMR 13.17, 22.93, 24.93, 58.92, 123.23,
142.04.
1-((ter t-Bu tyldiph en ylsilyl)oxy)-3-m eth yl-2-bu ten e (18).
3-Methyl-2-buten-1-ol (1.5 g, 17.4 mmol) was protected as the
TBDPS ether using the procedure described for the prepara-
tion of 6. Ether 18 was obtained (4.6 g, 14.2 mmol, 82%): GC
22.2 min; IR (neat) cm-1 3071, 2931, 2857, 1590, 1112; 1H NMR
(2E,6E)-1-((ter t-Bu t yld ip h en ylsilyl)oxy)-7-(ch lor om e-
th yl)-3-eth yl-2,6-n on a d ien e (17b). Alcohol 16b (1.35 g, 3.1
mmol) was converted to the allylic chloride using the procedure
described for the preparation of 17a . Chloride 17b was
obtained (1.35 g, 3.0 mmol, 97%): 1H NMR 0.86 (t, 3H, J )
7.6 Hz), 0.93-1.06 (m, 12H), 1.87 (q, 2H, J ) 7.5 Hz), 2.03-
2.26 (m, 6H), 4.07 (br s, 2H), 4.25 (d, 2H, J ) 6.2 Hz), 5.36 (t,
1H, J ) 6.1 Hz), 5.51 (t, 1H, J ) 6.8 Hz), 7.37-7.46 (m, 6H),

Terpenoid Precursors of Insect J uvenile Hormone
J . Org. Chem., Vol. 62, No. 11, 1997 3535
1.07 (s, 9H), 1.48 (s, 3H), 1.72 (s, 3H), 4.22 (d, 2H, J ) 6.3
Hz), 5.41 (t, 1H, J ) 6.1 Hz), 7.38-7.47 (m, 6H), 7.71-7.74
(m, 4H); 13C NMR 17.9, 19.2, 25.7, 26.8, 61.1, 124.2, 127.6,
129.5, 133.8, 134.1, 135.6.
(t, 1H, J ) 6.2 Hz), 5.49 (t, 1H, J ) 8.1 Hz); 13C NMR 14.4,
17.7, 24.4, 26.4, 27.4, 41.4, 42.8, 121.9, 124.8, 139.3, 144.4.
(2E,6Z)-1-Ch lor o-3-eth yl-7-m eth yl-2,6-n on a d ien e (23b).
From 9b (82 mg, 0.45 mmol), 23b was obtained (75 mg, 0.37
mmol, 82%): 1H NMR 0.96 (t, 3H, J ) 7.4 Hz), 1.02 (t, 3H,
J ) 7.4 Hz), 1.68 (s, 3H), 1.98-2.17 (m, 8H), 4.11 (d, 2H, J )
8.1 Hz), 5.07 (t, 1H, J ) 6.6 Hz), 5.41 (t, 1H, J ) 8.1 Hz); 13C
NMR 12.8, 13.3, 22.8, 23.3, 24.8, 26.0, 37.1, 41.2, 120.2, 123.7,
138.1, 148.8.
(E)-4-((ter t-Bu tyld ip h en ylsilyl)oxy)-2-m eth yl-2-bu ten -
1-ol (19). To a mixture of SeO2 (480 mg, 4.3 mmol), salicylic
acid (400 mg, 2.9 mmol), H2O (1.9 mL, 11 mmol), and t-BuOOH
(5.0-6.0 M in nonane, 8.5 mL, approximately 42 mmol) in CH2-
Cl2 (90 mL) which had stirred in the dark at rt for 30 min was
added 18 (4.6 g, 14.2 mmol) in CH2Cl2 (5 mL). The reaction
was stirred for 20 h at rt and poured into saturated aqueous
NaHCO3 (30 mL). The organic layer was then treated to the
standard workup, and the resulting oil was chromatographed
using EtOAc/hexane (10/90) as eluent to yield 19 (1.8 g, 5.3
mmol, 37%), 0.7 g of the corresponding aldehyde, and 0.5 g of
recovered 18: GC 24.8 min; IR (neat) cm-1 3365, 3072, 2931,
2858, 1694, 1651, 1428, 1112; 1H NMR 1.06 (s, 9H), 1.49 (s,
3H), 3.97 (s, 2H), 4.29 (d, 2H, J ) 6.1 Hz), 5.63 (t, 1H, J ) 5.6
Hz), 7.37-7.47 (m, 6H), 7.69-7.72 (m, 4H); 13C NMR 13.8,
19.2, 26.9, 60.8, 68.3, 124.9, 127.7, 129.6, 133.9, 135.6, 136.2.
(E)-1-((ter t-Bu tyld ip h en ylsilyl)oxy)-4-br om o-3-m eth yl-
2-bu ten e (20a ). Alcohol 19 (1.0 g, 2.9 mmol) was brominated
using the procedure described for the preparation of 17a ,
where LiBr was used in place of LiCl. Bromide 20a was
obtained (1.0 g, 2.5 mmol, 86%): 1H NMR 1.06 (s, 9H), 1.59
(s, 3H), 4.00 (s, 2H), 4.25 (d, 2H, J ) 6.0 Hz), 5.81 (t, 1H, J )
6.1 Hz), 7.36-7.48 (m, 6H), 7.66-7.71 (m, 4H); 13C NMR
16.6, 20.8, 28.4, 42.3, 62.7, 129.3, 131.3, 131.9, 134.5, 135.2,
137.2.
(2E)-1-Ch lor o-3-et h yl-7-m et h yl-2,6-oct a d ien e
(23c).
From 9c (54 mg, 0.32 mmol), 23c was obtained (50 mg, 0.27
mmol, 84%): 1H NMR 1.03 (t, 3H, J ) 7.7 Hz), 1.61 (s, 3H),
1.69 (s, 3H), 2.08-2.17 (m, 6H), 4.11 (d, 2H, J ) 8.1 Hz), 5.10
(t, 1H, J ) 6.6 Hz), 5.40 (t, 1H, J ) 8.1 Hz); 13C NMR 13.2,
17.6, 23.2, 25.6, 26.3, 36.3, 40.7, 119.7, 123.6, 131.8, 148.3.
(Z)-1-Ch lor o-3-m eth yl-2-p en ten e. From (Z)-3-methyl-2-
penten-1-ol (40 mg, 0.40 mmol), (Z)-1-chloro-3-methyl-2-pen-
tene was obtained (38 mg, 0.32 mmol, 80%): 1H NMR 1.03
(t, 3H, J ) 7.6 Hz), 1.77 (s, 3H), 2.13 (q, 2H, J ) 7.6 Hz), 4.09
(d, 2H, J ) 8.1 Hz), 5.41 (t, 1H, J ) 8.0 Hz).
Gen er a l P r oced u r e for th e P r ep a r a tion of Allylic
Dip h osp h a tes 2a -d a n d 1b: (2E)-3,7-Dim eth yl-2,6-octa -
d ien -1-yl Dip h osp h a te (Ger a n yl Dip h osp h a te, 2d ). To a
solution of geranyl chloride (80 mg, 0.46 mmol) in CH3CN (5
mL) was added tris(tetra-n-butyl)ammonium hydrogen diphos-
phate (830 mg, 0.9 mmol). After the solution was stirred at
rt for 3 h, the solvent was stripped at rt by rotary evaporation
at high vacuum to give approximately 900 mg of a white taffy
solid. This material was dissolved in 25 mM NH4HCO3/2-
propanol (49:1, 2 mL) and applied to a 20 × 1.5 cm Dowex
Meth yl (E)-4-((ter t-Bu tyld ip h en ylsilyl)oxy)-2-eth yl-2-
bu ten -1-oa te (21). To a solution of 6 (3.0 g, 4.9 mmol) in THF
(70 mL) at -40 °C was added n-BuLi (1.6 M in hexanes, 3.5
mL, 5.6 mmol) over 5 min, and after being stirred for 1 h at
-40 °C, a clear yellow solution was obtained. The reaction
was cooled to -78 °C and transferred by cannula over 10 min
into a solution of methyl chloroformate (2 mL, 25.9 mmol) in
THF (10 mL) at -78 °C. After the solution was stirred for 1
h at -78 °C, the reaction was quenched by the addition of H2O
(40 mL) and the solution was extracted with Et2O (3 × 20 mL).
The combined organic extracts were then subjected to the
standard workup. Chromatography using EtOAc/hexane (2/
98) as eluent yielded 21 (1.4 g, 3.6 mmol, 74%): GC 24.2 min;
+
50WX8-200 (NH4 form) column. Cation exchange was con-
ducted at a flow rate of 1 mL/min, and the eluent was collected
in 2.5 mL fractions with the product eluting between 10 and
20 mL. The diphosphate-containing fractions were diluted
with 2-propanol (4 mL), concentrated in vacuo, and the
resulting solid was purified by cellulose chromatography using
5:2.5:2.5 (v/v/v) 2-propanol/CH3CN/0.1 M NH4HCO3 as eluent
1
to give pure GPP as a white solid (80 mg, 0.22 mmol, 48%, H
and 13C NMR are consistent with those of authentic geranyl
diphosphate): 31P NMR -10.23, -6.97. The allylic diphos-
phate was dissolved in 1:1 0.25 mM NH4HCO3/2-propanol and
stored in this form at -20 °C for several months.
1
IR (neat) cm-1 3071, 2932, 2858, 1718, 1651, 1586, 1115; H
(2E,6Z)-3,7-Dim et h yl-2,6-n on a d ien -1-yl Dip h osp h a t e
(2a ). From chloride 9a (55 mg, 0.29 mmol), 2a was obtained
(40 mg, 0.10 mmol, 34%): 1H NMR 0.98 (t, 3H, J ) 6.4 Hz),
1.71 (s, 3H), 1.74 (s, 3H), 1.79-2.21 (m, 6H), 4.50 (dd, 2H, J )
6.6, 6.6 Hz), 5.21 (t, 1H, J ) 6.0 Hz), 5.48 (t, 1H, J ) 6.6 Hz);
13C NMR 12.3, 15.7, 22.1, 24.5, 25.3, 39.2, 62.6, 120.0 (d, 7.3
Hz), 123.8, 139.9, 142.8; 31P NMR -10.16, -7.91.
NMR 0.87 (t, 3H, J ) 7.4 Hz), 1.02 (s, 9H), 2.12 (q, 2H, J )
7.4 Hz), 3.76 (s, 3H), 4.38 (d, 2H, J ) 5.9 Hz), 6.85 (t, 1H, J )
5.9 Hz), 7.38-7.45 (m, 6H), 7.67-7.70 (m, 4H); 13C NMR
15.2, 20.8, 22.1, 28.3, 53.4, 62.5, 129.4, 131.5, 134.9, 135.1,
137.2, 142.4, 169.5.
(E)-4-((ter t-Bu t yld ip h en ylsilyl)oxy)-2-et h yl-2-b u t en -
1-ol (22). Ester 21 (1.4 g, 3.6 mmol) was reduced with
DIBALH using the procedure described for the preparation of
5. Alcohol 22 was obtained (1.0 g, 2.7 mmol, 75%): GC 24.0
min; IR (neat) cm-1 3334, 3071, 2942, 1669, 1586, 1110; 1H
NMR 0.89 (t, 3H, J ) 7.4 Hz), 1.06 (s, 9H), 1.94 (q, 2H, J )
7.4 Hz), 4.04 (s, 2H), 4.30 (d, 2H, J ) 6.6 Hz), 5.61 (t, 1H, J )
5.9 Hz), 7.37-7.44 (m, 6H), 7.69-7.72 (m, 4H); 13C NMR
13.3, 19.1, 21.2, 26.8, 60.4, 66.1, 124.8, 127.6, 129.6, 133.8,
135.6, 142.0.
(E)-1-((ter t-Bu tyld ip h en ylsilyl)oxy)-3-(br om om eth yl)-
2-p en ten e (20b). Alcohol 22 (1.0 g, 2.7 mmol) was brominated
using the procedure described for the preparation of 20a .
Bromide 20b was obtained (950 mg, 2.3 mmol, 85%): 1H NMR
0.92 (t, 3H, J ) 7.7 Hz), 1.06 (s, 9H), 2.04 (q, 2H, J ) 7.6
Hz), 4.00 (s, 2H), 4.26 (d, 2H, J ) 6.6 Hz), 5.79 (t, 1H, J ) 5.9
Hz), 7.37-7.45 (m, 6H), 7.68-7.71 (m, 4H); 13C NMR 14.3,
20.8, 23.3, 28.4, 39.7, 62.2, 129.3, 131.3, 131.9, 135.2, 137.2,
140.1.
P r ep a r a tion of Allylic Ch lor id es 23a -c a n d (Z)-1-
Ch lor o-3-m eth yl-2-p en ten e. Alcohols 9a -c and (Z)-3-meth-
yl-2-penten-1-ol were converted to the corresponding allylic
chlorides using the procedure described for the preparation of
17a .
(2E,6Z)-3-E t h yl-7-m et h yl-2,6-n on a d ien -1-yl Dip h os-
p h a te (2b). From chloride 9b (20 mg, 0.10 mmol), 2b was
obtained (9 mg, 0.02 mmol, 23%): 1H NMR 0.98 (t, 3H, J )
7.6 Hz), 1.00 (t, 3H, J ) 7.0 Hz), 1.71 (s, 3H), 2.03-2.22 (m,
8H), 4.51 (dd, 2H, J ) 6.4, 6.4 Hz), 5.23 (t, 1H, J ) 6.3 Hz),
5.45 (t, 1H, J ) 7.2 Hz); 13C NMR 12.3, 13.0, 22.2, 23.1, 24.5,
25.6, 36.2, 62.5, 119.6 (d, J ) 8.5 Hz), 124.0, 139.8, 148.7; 31
NMR -9.65, -6.85.
P
(2E)-3-Eth yl-7-m eth yl-2,6-octa d ien -1-yl Dip h osp h a te
(2c). From chloride 9c (25 mg, 0.13 mmol), 2c was obtained
(25 mg, 0.08 mmol, 61%): 1H NMR 1.01 (t, 3H, J ) 7.7 Hz),
1.66 (s, 3H), 1.72 (s, 3H), 2.11-2.22 (m, 6H), 4.52 (dd, 2H, J )
6.4, 6.4 Hz), 5.20-5.28 (m, 1H), 5.45 (t, 1H, J ) 7.2 Hz); 13C
NMR 13.1, 17.1, 23.2, 25.0, 25.9, 35.9, 62.4, 119.6 (d, J )
7.3 Hz), 124.4, 133.7, 148.7; 31P NMR -9.89, -8.01.
(2Z)-3-Meth yl-2-p en ten -1-yl Dip h osp h a te (1b). From
(Z)-1-chloro-3-methyl-2-pentene (70 mg, 0.60 mmol), 1b was
obtained (52 mg, 0.17 mmol, 34%): 1H NMR 0.99 (t, 3H, J
) 7.5 Hz), 1.77 (s, 3H), 2.17 (q, 2H, J ) 7.4 Hz), 4.49 (dd, 2H,
J ) 6.2, 6.2 Hz), 5.46 (t, 1H, J ) 6.0 Hz); 13C NMR 12.6,
22.3, 24.7, 62.5 (d, J ) 4.9 Hz), 119.2 (d, J ) 7.3 Hz), 146.0;
31P NMR -9.85, -7.93.
Gen er a l P r oced u r e for th e P r ep a r a tion of 3a -h .
BaI2‚2H2O (141 mg, 0.33 mmol) was placed in an amber vial
and dried in vacuo for 2 h at 210 °C. Upon cooling to rt, the
solid was immediately transferred to an Ar-filled flask equipped
with a stir bar and suspended in THF (10 mL), and a solution
(2E,6Z)-1-Ch lor o-3,7-d im et h yl-2,6-n on a d ien e
(23a ).
From 9a (76 mg, 0.45 mmol), 23a was obtained (73 mg, 0.39
mmol, 87%): 1H NMR 0.96 (t, 3H, J ) 7.7 Hz), 1.68 (s, 3H),
1.73 (s, 3H), 1.98-2.12 (m, 6H), 4.10 (d, 2H, J ) 8.8 Hz), 5.05

3536 J . Org. Chem., Vol. 62, No. 11, 1997
Sen and Ewing
of biphenyl radical anion (prepared by adding excess Li wire
(20 mg, 2.9 mmol) to a solution of biphenyl (105 mg, 0.68 mmol)
in THF (2.7 mL)) was added dropwise. After the solution was
stirred at rt for 1 h, the dark brown suspension was cooled to
-78 °C and chloride 23 (0.27 mmol) in THF (2 mL) was added
over 10 min. The resulting red solution was stirred at -78
°C for 15 min. Bromide 20 (0.31 mmol) in THF (2 mL) was
then added dropwise over 5 min, during which time the color
began to fade to a faint yellow. The reaction was stirred at
-78 °C for1 h and then quenched by the addition of saturated
aqueous NH4Cl (2 mL). The solution was diluted with H2O
(20 mL) and extracted with Et2O (3 × 10 mL), and the
combined organics were subjected to standard workup. Chro-
matography using EtOAc/hexane (1/99) as eluent yielded
isomerically impure 24 which was deprotected with TBAF
using the procedure described for the preparation of 9c.
Chromatography using EtOAc/hexane (15/85) as eluent fol-
lowed by reverse phase semipreparative HPLC (20/80 H2O/
CH3CN) provided pure 3a -h .
(2E,6E)-3,7,11-Tr im eth yl-2,6,10-d od eca tr ien -1-ol (3a ).
Farnesol (3a ) was obtained (22 mg, 0.10 mmol, 37%): GC 18.2
min; IR, 1H and 13C NMR are consistent with those of
authentic farnesol.
(2E,6E,10Z)-3,7,11-Tr im et h yl-2,6,10-t r id eca t r ien -1-ol
(3b). Alcohol 3b was obtained (18 mg, 0.08 mmol, 30%): GC
19.0 min; IR (neat) cm-1 3348, 2919, 1665; 1H NMR 0.96 (t,
3H, J ) 7.7 Hz), 1.60 (s, 3H), 1.68 (s, 6H), 1.99-2.16 (m, 10H),
4.15 (d, 2H, J ) 6.6 Hz), 5.04-5.09 (m, 2H), 5.42 (t, 1H, J )
6.6 Hz); 13C NMR 14.8, 17.9, 19.3, 24.8, 27.3, 27.6, 28.5, 38.1,
41.5, 61.0, 124.9, 125.0, 126.1, 132.9, 141.5, 142.9.
(2E,6E,10Z)-3,7-Dieth yl-11-m eth yl-2,6,10-tr id eca tr ien -
1-ol (3h ). Alcohol 3h was obtained (27 mg, 0.1 mmol, 38%):
GC 20.6 min; IR (neat) cm-1 3373, 2917, 1669; 1H NMR 0.96
(t, 3H, J ) 7.4 Hz), 0.99 (t, 6H, J ) 7.4 Hz), 1.68 (s, 3H), 1.99-
2.13 (m, 14H), 4.16 (d, 2H, J ) 7.3 Hz), 5.08 (t, 2H, J ) 5.9
Hz), 5.38 (t, 1H, J ) 7.0 Hz); 13C NMR 14.4, 14.8, 15.3, 24.5,
24.8, 25.2, 26.4, 27.8, 28.2, 38.3, 38.4, 60.7, 124.4, 125.0, 125.7,
138.7, 142.9, 147.4. Anal. Calcd for C18H32O: C, 81.75; H
12.19. Found: C, 81.85; H, 12.14.
In Vitr o Stu d ies. Assays were performed using previously
published assay procedures.1 Corpora cardiaca-corpora allata
complexes were removed from fifth instar M. sexta larvae and
immediately placed in a cold solution of 20 mM Tris-HCl
buffer (pH 7), containing 25% glycerol, 0.15% BSA, 2% Triton
X-100 (all w/v), 2.5 mM MgCl2, 10 mM KF, and 0.5 mM
mercaptoethanol. The glands were homogenized on ice and
after removal of cellular debris by centrifugation at 16000g
for 10 min, 50 L aliquots of supernatant (containing ap-
proximately two gland pair equivalents) were placed into
siliconized 500 L plastic microcentrifuge tubes. Prenyltrans-
ferase activity was determined by incubating the partially
purified homogenate in the presence of 100 M allylic diphos-
phate (1a ,b or 2a -d ) and 6 M [4-14C]IPP at 35 °C for 2 h.
The reaction was terminated by heating the solution to 100
°C for 1 min, and the diphosphates were hydrolyzed to the
corresponding terpenols by reaction with alkaline phosphatase
(8 units in 30 L of 100 mM Tris-HCl, 30 mM MgCl2, pH 9.5,
overnight at room temperature or 4 h at 37 °C).
P r od u ct An a lysis. Terpenol formation was determined by
radio-HPLC. After phosphatase treatment, the reaction mix-
ture was diluted with a stock solution of acetonitrile (80 L)
containing appropriate terpenol standards. A portion of the
aqueous acetonitrile solution from each assay tube (ap-
proximately 80 L) was injected onto a C-18 reversed phase
column (2.5 × 15 cm) and eluted with a two-step CH3CN/H2O
gradient (1 mL/min, 60 to 70% CH3CN over 10 min, 70 to 80%
CH3CN over 20 min, then isocratic at 80% CH3CN for 15 min).
Under these conditions, the following retention times for each
of the terpenols were obtained: dimethylallyl alcohol, 3.3 min;
homodimethylallyl alcohol, 4.3 min; geraniol, 5.5 min; 9a , 9c,
7.4 min; 9b, 11.1 min; farnesol (3a ), 13.0 min; 3b, 3c, 3d , 18.5
min; 3e, 3f, 3g, 22.3 min; 3h , 25.2 min. The eluents were
collected directly into scintillation vials (1 mL fractions) and
then analyzed by liquid scintillation counting. Relative activ-
ity was determined by normalizing each of the conversions
against those obtained with GPP (for 2a -d ) or DMAPP (for
1a ,b). Results were the average of three separate experiments
performed in duplicate.
(2E,6E)-3,11-Dim et h yl-7-et h yl-2,6,10-d od eca t r ien -1-ol
(3c). Alcohol 3c was obtained (20 mg, 0.08 mmol, 31%): GC
19.1 min; IR (neat) cm-1 3316, 2913, 1669; 1H NMR 0.96 (t,
3H, J ) 7.7 Hz), 1.59 (s, 3H), 1.67 (s, 3H), 1.68 (s, 3H), 1.95-
2.13 (m, 10H), 4.15 (d, 2H, J ) 7.4 Hz), 5.06 (t, 1H, J ) 6.6
Hz), 5.11 (t, 1H, J ) 5.9 Hz), 5.42 (t, 1H, J ) 7.0 Hz); 13C
NMR 14.4, 17.6, 17.9, 24.5, 26.4, 27.9, 41.2, 41.6, 61.0, 124.9,
125.4, 125.5, 137.0, 138.7, 141.5.
(2E,6E)-7,11-Dim et h yl-3-et h yl-2,6,10-d od eca t r ien -1-ol
(3d ). Alcohol 3d was obtained (19 mg, 0.08 mmol, 30%): GC
19.1 min; IR (neat) cm-1 3310, 2919, 1669; 1H NMR 0.99 (t,
3H, J ) 7.7 Hz), 1.60 (s, 6H), 1.68 (s, 3H), 1.98-2.13 (m, 10H),
4.16 (d, 2H, J ) 6.6 Hz), 5.07-5.12 (m, 2H), 5.38 (t, 1H, J )
7.0 Hz); 13C NMR 15.3, 17.6, 19.3, 25.1, 27.3, 28.1, 28.3, 38.0,
41.3, 60.7, 124.4, 125.5, 125.9, 133.0, 137.0, 147.4.
(2E,6E,10Z)-7-Eth yl-3,11-d im eth yl-2,6,10-tr id eca tr ien -
1-ol (3e). Alcohol 3e was obtained (24 mg, 0.1 mmol, 37%):
GC 19.9 min; IR (neat) cm-1 3331, 2921, 1668; 1H NMR 0.95
(t, 6H, J ) 7.3 Hz), 1.68 (s, 6H), 1.98-2.14 (m, 12H), 4.15 (d,
2H, J ) 7.4 Hz), 5.07 (t, 2H, J ) 6.3 Hz), 5.42 (t, 1H, J ) 7.0
Hz); 13C NMR 14.4, 14.8, 17.9, 24.5, 24.8, 26.4, 27.6, 28.2,
38.4, 41.5, 61.0, 124.9, 125.7, 138.7, 141.5, 142.9.
Ack n ow led gm en t . This work was supported
by USDA-NRICGP (USDA 92-3702-8128), Indiana
UniversitysPurdue University at Indianapolis, and by
The Purdue Research Foundation. We thank Michelle
Childress for technical assistance in M. sexta corpora
allata dissections.
(2E,6E,10Z)-3-Eth yl-7,11-d im eth yl-2,6,10-tr id eca tr ien -
1-ol (3f). Alcohol 3f was obtained (25 mg, 0.1 mmol, 37%):
GC 20.0 min; IR (neat) cm-1 3320, 2917, 1671; 1H NMR 0.96
(t, 3H, J ) 7.4 Hz), 0.99 (t, 3H, J ) 7.4 Hz), 1.60 (s, 3H), 1.67
(s, 3H), 1.95-2.13 (m, 12H), 4.16 (d, 2H, J ) 6.6 Hz), 5.09 (t,
1H, J ) 7.4 Hz), 5.10 (t, 1H, J ) 6.6 Hz), 5.38 (t, 1H, J ) 7.0
Hz); 13C NMR 14.4, 15.3, 17.7, 24.5, 25.1, 26.4, 27.9, 28.1,
38.0, 41.6, 60.7, 124.4, 125.5, 136.9, 138.7, 147.4. Anal. Calcd
for C17H30O: C, 81.54; H 12.13. Found: C, 81.14; H, 12.21.
(2E,6E)-3,7-Diet h yl-11-m et h yl-2,6,10-d od eca t r ien -1-ol
(3g). Alcohol 3g was obtained (22 mg, 0.09 mmol, 33%): GC
19.8 min; IR (neat) cm-1 3342, 2918, 1669; 1H NMR 0.96 (t,
3H, J ) 7.4 Hz), 0.99 (t, 3H, J ) 7.4 Hz), 1.60 (s, 3H), 1.68 (s,
3H), 1.99-2.13 (m, 12H), 4.16 (d, 2H, J ) 7.3 Hz), 5.06-5.11
(m, 2H), 5.38 (t, 1H, J ) 6.6 Hz); 13C NMR 14.8, 15.3, 19.3,
24.8, 25.1, 27.3, 27.8, 28.5, 38.1, 38.3, 60.7, 124.4, 125.0, 126.1,
132.9, 142.9, 147.4.
Su p p or t in g In for m a t ion Ava ila b le: 1H and 13C NMR
spectra of all new compounds (as well 31P spectra of compounds
1b and 2a -c) in the Experimental Section (68 pages). This
material is contained in libraries on microfiche, immediately
follows this article in the microfilm version of the journal, and
can be ordered from the ACS; see any current masthead page
for ordering information.
J O962008Q