Simple synthesis of the major sex pheromone components of Drosophila ananassae and D. pallidosa

Article abstract of DOI:10.1271/bbb.69.1620

The major sex pheromone components of Drosophila ananassae and D. pallidosa, (Z,Z)-5,25-hentriacontadiene and (Z,Z)-5,27-tritriacontadiene, respectively, were synthesized by using the Wittig olefination and sulfone coupling reactions as the C-C bond-forming steps.

Full text of DOI:10.1271/bbb.69.1620

Biosci. Biotechnol. Biochem., 69 (8), 1620–1623, 2005
Note
Simple Synthesis of the Major Sex Pheromone Components
of Drosophila ananassae and D. pallidosa
y
1;
Akira MORITA,1 Shigeru MATSUYAMA,2 Yuzuru OGUMA,3 and Shigefumi KUWAHARA
1Laboratory of Applied Bioorganic Chemistry, Graduate School of Agricultural Science,
Tohoku University, 1-1 Tsutsumidori-Amamiyamachi, Aoba-ku, Sendai 981-8555, Japan
2Institute of Applied Biochemistry, University of Tsukuba, Tsukuba, Ibaraki 305-8572, Japan
3Division of Structural Biosciences, Graduate School of Life and Environmental Sciences,
University of Tsukuba, Tsukuba, Ibaraki 305-8572, Japan
Received March 24, 2005; Accepted April 28, 2005
The major sex pheromone components of Drosophila
ananassae and D. pallidosa, (Z,Z)-5,25-hentriaconta-
diene and (Z,Z)-5,27-tritriacontadiene, respectively,
were synthesized by using the Wittig olefination and
sulfone coupling reactions as the C–C bond-forming
steps.
the two components is also considered to be a key factor
in premating isolation between the two species.1,2) It is
now expected that the identification of genes controlling
the pheromone production and recognition could pro-
vide a genetic basis for sexual isolation, leading
eventually to understanding the mechanism of speci-
ation.5) To promote such studies by using a model
system composed of the two sympatric sibling species,
the supply of sufficient amounts of the pheromone
samples (1 and 2) is badly needed, which prompted us to
develop a simple synthetic route to 1 and 2.
The synthesis of 1 and 2 has previously been reported
in brief without any experimental details by Nemoto et
al.1,2) They employed the Grignard coupling reaction of
C and D as the final step in the synthesis of 2, which
brought about undesirable homo-coupled hydrocarbon
byproducts, making them use labor-intensive prepara-
tive GLC to purify the final product.1) With this in mind,
we planned our synthesis of 1 and 2 as shown in
Scheme 1. In order to obtain 1, bromoalcohol 3a6) was
converted, without protecting its hydroxyl group, into
sulfone 4a by treating with the anion derived from
methyl phenyl sulfone.7) The Swern oxidation of 4a to
Key words: pheromone; Drosophila ananassae; Droso-
phila pallodosa; fruit fly
Two closely related fruit flies, Drosophila ananassae
and D. pallidosa, are known to be sympatric but to show
no postmating isolation.1,2) The difference in the court-
ship song between the two species has recently been
revealed to play a crucial role in premating sexual
isolation between them,3) and the genetic background
of the difference in the courtship song has gradually
been elucidated.4) On the other hand, two long-chain
alkadienes, (5Z,25Z)-5,25-hentriacontadiene (1) and
(5Z,27Z)-5,27-tritriacontadiene (2) (Scheme 1), are
known as the major sex pheromone components in
female cuticular extracts of D. ananassae and D. pallid-
osa, respectively, and the difference in the contents of
Scheme 1. Reagents: a) PhSO2Me, n-BuLi, THF–HMPA (97% for 4a, 88% for 4b); b) DMSO, (COCl)2, Et3N, CH2Cl2 (quant. for 5a, 99% for 5b);
.
c) Ph3P(CH2)5Me Br, KHMDS, THF–HMPA (92% for 6a, 91% for 6b); d) n-BuLi, B, THF–HMPA (70% for 7a and 62% for 7b); e) SmI2,
THF–HMPA (74% for 1, 76% for 2); f) Br2, Ph3P, Py, CH2Cl2 (96%).
y
To whom correspondence should be addressed. Tel/Fax: +81-22-717-8783; E-mail: skuwahar@biochem.tohoku.ac.jp

Synthesis of Fruit Fly Pheromones
1621
aldehyde 5a was followed by exposure to Z-selective
Wittig olefination conditions8) to afford olefin 6a, whose
geometrical homogeneity was checked by its 13C-NMR
spectrum, in which no peak other than those assignable
to 6a was observed. The coupling of sulfone 6a and
bromide B,9) which had been prepared by LiAlH4-
reduction of commercially available (Z)-11-hexadecenal
(Aldrich, >95% purity) and subsequent bromination of
the resulting alcohol (A), gave 7a possessing all the
carbon atoms and appropriately arranged double bonds
for 1. Reductive removal of the sulfonyl moiety was first
attempted by treating 7a with an excess amount of
lithium in ethylamine at ꢀ15 ꢁC for 1 hour.7) This
reduction method, however, brought about partial over-
reduction, giving substantial amounts of two corre-
sponding monoene products. Eventually, the reductive
elimination reaction was effected cleanly with sama-
rium(II) iodide in THF–HMPA10) to furnish 1 in a 74%
yield after SiO2–AgNO3 chromatographic purification.
By following the same five-step sequence of reactions, 2
was obtained from 3b via 4b, 5b, 6b and 7b. The overall
yields of 1 and 2 were 46% and 37%, respectively.
2.83 mmol) in dichloromethane (8 ml) was added, and
the mixture was stirred for 30 min. To this mixture was
then added Et3N (2.0 ml, 14.4 mmol), and the resulting
mixture was gradually warmed to room temperature,
poured into water and extracted with ether. The ethereal
solution was successively washed with water and brine,
dried (MgSO4) and concentrated in vacuo. The residue
was chromatographed over silica gel (20 g; hexane–ethyl
acetate, 3:1) to give 0.797 g (quant.) of 5a; IR
ꢀ
max cmꢀ1: 3050 (w), 3000 (m), 2715 (m), 1712 (s),
1300 (s), 1140 (s); 1H-NMR (300 MHz) ꢁ: 1.22–1.42
(8H, m), 1.60 (2H, qui, J ¼ 7:3 Hz), 1.65–1.77 (2H, m),
2.41 (2H, dt, J ¼ 1:8, 7.4 Hz), 3.04–3.11 (2H, m), 7.55–
7.61 (2H, m), 7.64–7.70 (1H, m), 7.90–7.93 (2H, m),
9.76 (1H, t, J ¼ 1:8 Hz); HR-FABMS m=z (½M þ Hꢂþ):
calcd. for C15H23O3S, 283.1368; found, 283.1372.
(Z)-15-Benzenesulfonyl-6-pentadecene (6a). To
a
stirred suspension of hexyltriphenylphosphonium bro-
mide (0.456 g, 1.07 mmol) in THF–HMPA (3:1, 8 ml)
was added dropwise a solution of potassium hexa-
methyldisilazide (KHMDS) in toluene (0.7 M, 1.50 ml,
1.05 mmol) at 0 ꢁC. After 30 min, a solution of 5a
(0.221 g, 0.713 mmol) in THF (4 ml) was added at
ꢀ78 ꢁC, and the mixture was stirred for 30 min. The
reaction mixture was gradually warmed to room temper-
ature, poured into sat. NH4Cl aq. and extracted with
ether. The ethereal solution was successively washed
with water and brine, dried (MgSO4) and concentrated
in vacuo. The residue was chromatographed over silica
gel (5 g; hexane–ethyl acetate, 5:1) to give 0.252 g
(94%) of 6a; IR ꢀmax cmꢀ1: 3050 (w), 2990 (m), 1580
(w), 1300 (s), 1140 (s); 1H-NMR (300 MHz) ꢁ: 0.88 (3H,
t, J ¼ 6:9 Hz), 1.20–1.40 (16H, m), 1.65–1.76 (2H, m),
1.95–2.04 (4H, m), 3.05–3.11 (2H, m), 5.28–5.40 (2H,
m), 7.54–7.61 (2H, m), 7.64–7.70 (1H, m), 7.90–7.94
(2H, m); 13C-NMR (125 MHz) ꢁ: 14.07, 22.56, 22.60,
27.11, 27.15, 28.24, 28.96, 29.06, 29.11, 29.41, 29.61,
31.50, 56.29, 128.04, 129.23, 129.67, 130.02, 133.58,
139.19; HR-EIMS m=z (Mþ): calcd. for C21H34O2S,
350.2279; found, 350.2279.
Experimental
IR spectra were measured as films by a Jasco IR
Report-100 spectrometer. NMR spectra were recorded
with TMS as an internal standard in CDCl3 by a Varian
Gemini 2000 spectrometer (300 MHz) or a Varian
UNITYplus-500 spectrometer (500 MHz). GLC analyses
were performed on a Hewlett-Packard 6890 gas chro-
matograph. Merck silica gel 60 (70–230 mesh) was used
for silica gel column chromatography.
9-Benzenesulfonyl-1-nonanol (4a). To a stirred solu-
tion of methyl phenyl sulfone (2.25 g, 14.4 mmol) in
THF–HMPA (10:1, 66 ml) was added dropwise a
solution of butyllithium in hexane (1.6 M, 9.0 ml, 14.4
mmol) at ꢀ78 ꢁC. After 30 min, a solution of 3a
(0.995 g, 4.76 mmol) in THF (10 ml) was added, and
the resulting mixture was warmed gradually to room
temperature over 8 h. The mixture was poured into sat.
NH4Cl aq. and extracted with ether. The ethereal
solution was successively washed with water and brine,
dried (MgSO4) and concentrated in vacuo. The residue
was chromatographed over silica gel (40 g; hexane–ethyl
acetate, 10:1) to give 1.31 g (97%) of 4a as a white solid,
recrystallization of which from hexane-ethanol afforded
colorless flakes, mp 44.5–45.5 ꢁC; IR ꢀmax cmꢀ1: 3325
(s), 1580 (m), 1300 (s), 1140 (s); 1H-NMR (300 MHz) ꢁ:
1.20–1.40 (10H, m), 1.55 (2H, qui, J ¼ 7:1 Hz), 1.66–
1.76 (2H, m), 3.05–3.15 (2H, m), 3.64 (2H, t, J ¼
6:3 Hz), 7.55–7.94 (2H, m), 7.64–7.70 (1H, m), 7.90–
7.94 (2H, m); HR-FABMS m=z (½M þ Hꢂþ): calcd. for
C15H25O3S, 285.1525; found, 285.1529.
(Z)-16-Bromo-5-hexadecene (B). To a stirred solution
of triphenylphosphine (0.349 g, 1.33 mmol) in dichloro-
methane (4 ml) was added dropwise bromine (0.156 g,
0.976 mmol) at ꢀ30 ꢁC. After 30 min, a solution of A
(0.201 g, 0.836 mmol) and pyridine (0.10 ml, 1.24 mmol)
in dichloromethane (5 ml) was added dropwise, and the
reaction mixture was gradually warmed to room temper-
ature. The mixture was concentrated in vacuo, diluted
with pentane and filtered. The filtrate was concentrated
in vacuo, and the residue was chromatographed over
silica gel (5 g, hexane) to give 0.243 g (96%) of B; IR
ꢀ
max cmꢀ1: 3000 (m), 1650 (w), 720 (m), 661 (m), 641
1
(m); H-NMR (300 MHz) ꢁ: 0.90 (3H, t, J ¼ 7:2 Hz),
1.25–1.46 (18H, m), 1.86 (2H, qui, J ¼ 7:0 Hz), 1.97–
2.06 (4H, m), 3.41 (2H, t, J ¼ 7:0 Hz), 5.30–5.41 (2H,
m); 13C-NMR (125 MHz) ꢁ: 13.99, 22.34, 26.90, 27.17,
28.16, 28.76, 29.26, 29.42, 29.47, 29.49, 29.74, 31.95,
32.82, 34.06, 129.84, 129.86; HR-EIMS m=z (Mþ):
9-(Benzenesulfonyl)nonanal (5a). To a stirred solution
of oxalyl chloride (0.482 g, 3.80 mmol) in dichloro-
methane (30 ml) was added dropwise a solution of
DMSO (0.605 g, 7.75 mmol) in dichloromethane (6 ml)
at ꢀ78 ꢁC. After 10 min, a solution of 4a (0.804 g,

1622
A. MORITA et al.
calcd. for C16H3179Br, 302.1809; found, 302.1615.
are as follows: 4b (88% yield); mp 59.5–60 ꢁC (colorless
flakes); HR-FABMS m=z (½M þ Hꢂþ): calcd. for
C17H29O3S, 313.1837; found, 313.1843. 5b (99% yield);
mp 46.5–47.5 ꢁC (recrystallization from hexane);
HR-FABMS m=z (½M þ Hꢂþ): calcd. for C17H27O3S,
311.1681; found, 311.1681. 6b (91% yield); 13C-NMR
(125 MHz) ꢁ: 14.08, 22.56, 22.60, 27.15, 28.25, 28.98,
29.20, 29.22, 29.41, 29.42, 29.71, 31.50, 56.30, 128.04,
129.23, 129.80, 129.94, 133.59, 139.17 (only 19 of 21
peaks required for 6b were observed due to peak-
overlapping in the methylene carbon region); HR-EIMS
m=z (Mþ): calcd. for C23H38O2S, 378.2592; found,
378.2596. 7b (62% yield); HR-EIMS m=z (Mþ): calcd.
for C39H68O2S, 600.4940; found, 600.4940. 2 (76%
yield); 13C-NMR (125 MHz) ꢁ: 14.01, 14.08, 22.34,
22.58, 26.90, 27.12, 29.31, 29.45, 29.55, 29.65, 29.69,
29.70, 29.76, 31.52, 31.96, 129.83, 129.89, 129.91 (two
overlapping peaks) (only 18 of 33 peaks required for 2
were observed due to peak-overlapping in the methylene
region); GLC (under the same conditions as those
employed for 1): tR 29.91 min (98.2% purity); HR-
EIMS m=z (Mþ): calcd. for C33H64, 460.5008; found,
460.5009.
(5Z,25Z)-17-Benzenesulfonyl-5,25-hentriacontadiene
(7a). To a stirred solution of 6a (0.214 g, 0.610 mmol)
in THF–HMPA (30:1, 6.3 ml) was added dropwise a
solution of butyllithium in hexane (1.6 M, 0.385 ml,
0.616 mmol) at ꢀ78 ꢁC. One minute after the addition, a
solution of B (0.145 g, 0.478 mmol) in THF (3 ml) was
added, and the resulting mixture was gradually warmed
to room temperature, poured into sat. NH4Cl aq. and
extracted with ether. The ethereal solution was succes-
sively washed with water and brine, dried (MgSO4) and
concentrated in vacuo. The residue was chromatograph-
ed over silica gel (5 g; hexane–ethyl acetate, 200:1) to
give 0.193 g (70%) of 7a together with 40 mg of 6a and
34 mg of B; IR ꢀmax cmꢀ1: 3050 (w), 3000 (w), 1300
(m), 1140 (m); 1H-NMR (300 MHz) ꢁ: 0.89 (3H, t,
J ¼ 7:1 Hz), 0.90 (3H, t, J ¼ 7:1 Hz), 1.18–1.36 (36H,
m), 1.49–1.62 (2H, m), 1.76–1.88 (2H, m), 1.93–2.07
(2H, m), 2.89 (1H, tt, J ¼ 7:0, 4.9 Hz), 5.28–5.41 (4H,
m), 7.53–7.59 (2H, m), 7.62–7.68 (1H, m), 7.86–7.90
(2H, m); HR-EIMS m=z (Mþ): calcd. for C37H64O2S,
572.4627; found, 572.4629.
(5Z,25Z)-5,25-Hentriacontadiene (1). To neat sulfone
7a (67.2 mg, 0.117 mmol) was successively added a
solution of samarium(II) iodide in THF (0.1 M, 12.0 ml,
1.20 mmol) and HMPA (1.2 ml) at 30 ꢁC, and the
mixture was stirred for 1 h at the same temperature,
poured into sat. NH4Cl aq. and extracted with ether. The
ethereal solution was successively washed with water
and brine, dried (MgSO4) and concentrated in vacuo.
The residue was chromatographed over silica gel
impregnated with 1.5 wt. % of silver nitrate (2 g, hexane)
to give 37.6 mg (74%) of 1; IR ꢀmax cmꢀ1: 3000 (w),
2920 (s), 2850 (s), 1655 (w), 1465 (m), 1380 (w), 1120
(m), 720 (m), 670 (m); 1H-NMR (500 MHz) ꢁ: 0.89 (3H,
t, J ¼ 6:8 Hz), 0.90 (3H, t, J ¼ 6:8 Hz), 1.23–1.37 (42H,
m), 1.99–2.05 (8H, m), 5.32–5.39 (4H, m); 13C-NMR
(125 MHz) ꢁ: 14.00, 14.08, 22.35, 22.58, 26.90, 27.17,
27.19, 29.31, 29.45, 29.55, 29.65, 29.69, 29.77, 31.53,
31.97, 129.83, 129.89, 129.90 (two overlapping peaks)
(only 18 of 31 peaks required for 1 were observed due
to peak-overlapping in the methylene region); GLC
(Quadrex FFAP capillary column, 0:25 mm ID ꢃ 25 m,
0.25 mm film thickness; temperature, 50 ꢁC (1 min) + 8
ꢁC/min to 230 ꢁC (20 min); He carrier gas at 1 ml/min):
tR 26.47 min (97.2% purity); HR-EIMS m=z (Mþ):
calcd. for C31H60, 432.4695; found, 432.4704.
Acknowledgments
This work was supported, in part, by grant aid for
scientific research (B) from the Ministry of Education,
Culture, Sports, Science and Technology of Japan
(No. 16380075).
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