Syntheses of racemic and diastereomeric mixtures of 3,7,11,15- tetramethylhentriacontane and 4,8,12,16-tetramethyldotriacontane, the cuticular tetramethylalkanes of the tsetse fly, Glossina brevipalpis

Article abstract of DOI:10.1271/bbb.66.582

Cuticular hydrocarbons of the tsetse fly, Glossina brevipalpis, contain 3,7,11,15-tetramethylhentriacontane and 4,8,12,16-tetramethyldotriacontane as possible candidates for its contact sex pheromone. These were synthesized as racemic and diastereomeric mixtures starting from racemic citronellol and employing phenylsulfone-mediated chain-elongation as the key reaction.

Full text of DOI:10.1271/bbb.66.582

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Syntheses of Racemic and Diastereomeric Mixtures
of 3,7,11,15- Tetramethylhentriacontane and
4,8,12,16-Tetramethyldotriacontane, the Cuticular
Tetramethylalkanes of the Tsetse Fly,…
Chié SHIBATAa, Ayako FURUKAWAa & Kenji MORI
a Department of Chemistry, Faculty of Science, Science University of Tokyo Kagurazaka
1-3, Shinjuku-ku, Tokyo 162-8601, Japan
Published online: 22 May 2014.
To cite this article: Chié SHIBATA, Ayako FURUKAWA & Kenji MORI (2002) Syntheses of Racemic and Diastereomeric
Mixtures of 3,7,11,15- Tetramethylhentriacontane and 4,8,12,16-Tetramethyldotriacontane, the Cuticular
Tetramethylalkanes of the Tsetse Fly,…, Bioscience, Biotechnology, and Biochemistry, 66:3, 582-587, DOI: 10.1271/
bbb.66.582
To link to this article: http://dx.doi.org/10.1271/bbb.66.582
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Biosci. Biotechnol. Biochem., 66 (3), 582–587, 2002
Syntheses of Racemic and Diastereomeric Mixtures of 3,7,11,15-
Tetramethylhentriacontane and 4,8,12,16-Tetramethyldotriacontane,
the Cuticular Tetramethylalkanes of the Tsetse Fly, Glossina brevipalpis†
††
Chieá SHIBATA, Ayako FURUKAWA, and Kenji MORI
Department of Chemistry, Faculty of Science, Science University of Tokyo, Kagurazaka 1-3, Shinjuku-ku,
Tokyo 162-8601, Japan
Received October 1, 2001; Accepted October 30, 2001
Cuticular hydrocarbons of the tsetse ‰y, Glossina
brevipalpis, contain 3,7,11,15-tetramethylhentriacon-
tane and 4,8,12,16-tetramethyldotriacontane as possible
candidates for its contact sex pheromone. These were
synthesized as racemic and diastereomeric mixtures
starting from racemic citronellol and employing phenyl-
sulfone-mediated chain-elongation as the key reaction.
there is no stereoisomer to inhibit the bioactivity of
other isomer(s), we can expect good bioassay results
even with the stereoisomeric mixture of a phero-
mone.7) Indeed, in the case of G. tachinoides, a ra-
cemic and diastereomeric mixture of 11,23-dimethyl-
heptatriacontane was active as the sex stimulant
against male ‰ies.8) As shown in Scheme 1, our syn-
thetic plan for 1 and 2 is very simple. Target molec-
ules 1 and 2 with four methyl branchings are to be
dissected into two building blocks, A and B, each of
them possessing two methyl branchings. Alkylation
of phenylsulfone B with iodide A builds up the car-
bon skeleton of 1 and 2.cf.5) Both A and B can be syn-
Key words: cuticular hydrocarbon; Glossina brevipal-
pis; methyl-branched alkane; optically ac-
tive alkane; pheromone
The tsetse ‰y is known to spread the notorious
sleeping sickness in Africa, and is therefore a hazard
to the health of humans and cattle there. Their
pheromones are of considerable research interest
among medical entomologists, and a number of
methyl-branched hydrocarbons have been isolated as
their contact sex pheromones.1) We have been en-
gaged since 1980 in the synthesis of such tsetse ‰y
pheromones as those of Glossina morsitans morsi-
±
thesized from commercially available ( )-citronellol
(C).
Scheme 2 summarizes our syntheses of 1 and 2.
The preparation of building block 10 (one of A) will
be discussed ˆrst. (
to the known
±
±
)-Citronellol (3) was converted
)-2,6-dimethyl-1,8-diacetoxy-2-
(
2)
3)
4)
tans
,
G. pallidipes
,
G. tachinoides
,
and G.
5)
austeni
.
The synthesized pheromones were all
methyl-branched hydrocarbons with two3–5) or three2)
branchings.
Tetramethylalkanes are signiˆcant components of
the cuticular hydrocarbons of G. brevipalpis, while
in other tsetse ‰ies, they are only minor compo-
nents.6) 3,7,11,15-Tetramethylhentriacontane (1) and
4,8,12,16-tetramethyldotriacontane (2) are present in
both male and female G. brevipalpis,6) although their
biological role is not yet clear. In order to clarify this,
su‹cient amounts of 1 and 2 are required for subse-
quent biotesting. We therefore undertook the syn-
theses of 1 and 2.
The presence of four stereogenic centers in 1 and 2
means that they exist in sixteen stereoisomeric forms.
To avoid complication, we decided to synthesize both
1 and 2 as racemic and diastereomeric mixtures. If
Scheme 1. Structures of the Cuticular Hydrocarbons of the
Tsetse Fly, Glossina brevipalpis, and Their Retrosynthetic Anal-
ysis.
†
Pheromone Synthesis, Part 214. For Part 213, see Muto, S., and Mori, K., Eur. J. Org. Chem., 4635–4638 (2001).
To whom correspondence should be addressed at the following: Insect Pheromone and Traps Division, Fuji Flavor Co., Ltd.,
Midorigaoka 3-5-8, Hamura-City, Tokyo 205-8053, Japan. Fax: 81-42-555-7920
††

Syntheses of Two Tetramethylalkanes of the Tsetse Fly
583
±
Chain-elongation of ( )-citronellyl tosylate (15) with
tetradecylmagnesium bromide under Schlosser con-
ditions11) aŠorded ( )-2,6-dimethyl-2-docosene (16),
±
whose (
tion of (
hydroperoxide was followed by sodium borohydride
reduction of the resulting -unsaturated aldehyde
S
±
)-isomer is a known compound.14) Oxida-
)-16 with selenium dioxide and t-butyl
a, b
±
to give allylic alcohol ( )-17. Since hydrogenation of
17 over palladium-charcoal or platinum oxide was
unsuccessful under atmospheric pressure, 17 was
hydrogenated under medium pressure (3–4 kg cm2)
W
over Raney nickel (W 7) to give saturated alcohol 18
as a racemic and diastereomeric mixture. Alcohol 18
was then tosylated to give 19, which was converted to
phenylsulfone 21 via iodide 20. The overall yield of
±
z
based on ( )-citronellol (3, seven steps).
21 was 29
With the two building blocks A (10 or 14) and B
(21) in hand, these two were connected by alkylation
of the anion of phenylsulfone 21 with iodide 10 or 14
to give new phenylsulfone 22 or 23 in a 99
z z
or 93
yield. Finally, reductive removal of the phenylsul-
fonyl group of 22 and that of 23 with lithium in
ethylamine yielded the target molecules, 3,7,11,15-
tetramethylhentriacontane (1) and 4,8,12,16-tetra-
methyldotriacontane (2), in 83
respectively. The overall yield of 1 was 21
steps via 10) or 24 (nine steps via 21), and that of 2
was 17 (nine steps via 14) or 8 (nine steps via 21)
z
and 81
z
z
yields,
(nine
z
z
z
±
based on ( )-citronellol (3). Both 1 and 2 showed
spectral (1H-NMR and MS) properties and elemental
analytical data in good agreement with the struc-
tures.
Scheme 2. Syntheses of 1 and 2.
Reagents: (a) Ac2O, C5H5N (quant. for 4; 95
z
for 6). (b)
for 17
(2 steps)]. (c) MeMgBr (for 7) or EtMgBr (for 11), Li2CuCl4,
THF (63 for 7; 70 for 11). (d) H2, Pd–C, EtOH (86 for 8;
90 for 12). (e) TsCl, C5H5N. (f) NaI, DMF [95 for 10 (2
steps); 87 for 14 (2 steps)]. (g) Me(CH2)13MgBr, Li2CuCl4,
THF. (h) H2, Raney Ni (W 7), EtOH (quant.). (i) NaSO2Ph,
DMF [60 (3 steps)]. (j) -BuLi, THF, HMPA; then 10 or 14 in
for 22; 85 for 23). (k) Li, EtNH2 (83 for 1; 81
SeO2, t-BuOOH, CH2Cl2; then NaBH4 [53z for 5; 48z
In conclusion, racemic and diastereomeric mix-
tures of the two cuticular hydrocarbons, 1 and 2, of
the tsetse ‰y, Glossina brevipalpis, were synthesized.
Biological studies on 1 and 2 are now in progress by
Dr. D. A. Carlson at U.S. Department of Agricul-
ture.
z
z
z
z
z
z
z
z
n
THF (99
for 2).
z
z
z
Experimental
octene (6)9) via
(
)-citronellyl acetate (4) and
alcohol ( )-5 according to the method of Kefalas
and Ragoussis,10) who prepared (
)-5. Treatment of
)-6 with methylmagnesium bromide in the
presence of dilithium tetrachlorocuprate11) aŠorded
±
±
Melting point (mp) data were measured with a
Yanaco MP-S3 instrument and are uncorrected. IR
S
±
(
data were measured with a Jasco FT IR-410 spec-
W
1
trometer. H-NMR data were measured with a Jeol
±
±
alcohol ( )-7. Hydrogenation of ( )-7 over pal-
ladium-carbon gave alcohol 8 as a racemic and
diastereomeric mixture. It should be added that
JNM-AL300 (300 MHz), Jeol JNM-LA400 (400
MHz) or Jeol JNM-LA500 (500 MHz) spectrometer
(TMS at dH 0.00 or CHCl3 at dH 7.26 was used as
＝ ＝
(3
Alcohol 8 furnished iodide 10 (one of A) via tosylate
9. The overall yield of 10 was 26 based on 3 (seven
R
,7
R
)-8 and (3
R
,7
S
)-8 are known compounds.12)
the internal standard). MS data were measured with a
Jeol JMS-AX 505 HA spectrometer, and refractive
z
index (
nD) data were measured with an Atago DMT-1
steps). In the same manner, except that ethylmagnesi-
um bromide was employed for the conversion of 6 to
11, iodide 14 (the other of A) was synthesized from 3
overall yield (seven steps) via 11, 12 and 13.
Four optically active forms of 12 and 14 are known
refractometer.
±
(
) - (E) - 2,6 - Dimethyl - 1,8 - diacetoxy - 2 - octene
± ±
[( )-6]. To a stirred and ice-cooled solution of ( )-5
in a 24
z
(10.2 g, 47.7 mmol) in CH2Cl2 (40 ml) and pyridine
(11.6 ml, 143 mmol) was added Ac2O (6.80 ml,
71.5 mmol). After stirring for 5 h at room tempera-
compounds.13)
Another building block 21 (B) was also prepared.

584
C. SHIBATA et al.
ture, the mixture was poured into 1
M
HCl and ex-
C–O). NMR dH (400 MHz, CDCl3): 0.78–0.85 (6H,
＝
7.0 Hz, 9-H),
tracted with CH2Cl2. The combined organic phases
m, 3-Me, 7-Me), 0.88 (3H, t,
J
were successively washed with 1
M
HCl, water, a
1.03–1.42 (11H, m, 3-H, 4-H, 5-H, 6-H, 7-H, 8-H,
–OH), 1.53–1.65 (2H, m, 2-H), 3.61-3.74 (2H, m,
saturated aqueous NaHCO3 solution and brine, dried
with MgSO4, and concentrated in vacuo. The residue
was chromatographed on silica gel (200 g; hexane
1
1-H). The IR and H-NMR spectra are identical to
those in the literature.12)
W
±
AcOEt, 20:1) to give 11.7 g of ( )-6 (95
z) as a yel-
low oil, n2D5 1.4521 (lit.3) nD20 1.4530). IR nmax (ˆlm)
(
)-3,7-Dimethylnonyl Tosylate [( )-
9
]. To a
±
±
±
cm„1: 1740 (s, C O), 1240 (C–C( O)–O). NMR dH
(400 MHz, CDCl3): 0.92 (3H, d, 6.7 Hz, 6-Me),
stirred and ice-cooled solution of ( )-8 (2.10 g,
＝
＝
J
＝
12.2 mmol) in CH2Cl2 (20 ml) and pyridine (3.10 ml,
1.16–1.27 (1H, m, 6-H), 1.34–1.57 (4H, m, 5-H,
7-H), 1,61 (3H, s, 2-Me), 1.95 (3H, s, 1-Ac), 2.07
(3H, s, 8-Ac), 1.92–2.13 (2H, m, 4-H), 4.06–4.12
36.6 mmol) was added p-toluenesulfonyl chloride
(3.92 g, 20.6 mmol) in one portion. After stirring for
17 h at 4 C, the mixture was poured into water, and
9
＝
(2H, m, 8-H), 4.46 (2H, s, 1-H), 5.44 (1H, t,
J
7.7
the resulting mixture was extracted with Et2O. The
combined ethereal extracts were successively washed
1
Hz, 3-H). The IR and H-NMR spectra are identical
to those in the literature.9)
with 1
M
HCl, a saturated NaHCO3 solution and
brine, dried with MgSO4, and concentrated in vacuo
(
)-(E)-3,7-Dimethyl-6-nonen-1-ol [( )-
7
]. To a
to give 4.26 g of crude ( )-9. IR nmax (ˆlm) cm„1
:
±
±
±
±
＝
stirred and ice-cooled solution of ( )-6 (7.70 g,
1600 (m, aromatic), 1365 (m, S O), 1175 (m,
S–O–C). NMR dH (500 MHz, CDCl3): 0.80–0.86
(9H, m, 3-Me, 7-Me, 9-H), 1.00–1.33 (10H, m, 3-H,
4-H, 5-H, 6-H, 7-H, 8-H), 1.40–1.49 (1H, m 2-H),
1.64–1.67 (1H, m, 2-H), 2.45 (3H, s, Ar-Me),
30.0 mmol) in dry THF (70 ml) were added a solution
of MeMgBr in THF (1.00
M
, 120 ml, 120 mmol) and
, 5.00 ml,
C under argon. The mixture was
allowed to warm to 4 C over 3.5 h. It was then quen-
a solution of Li2CuCl4 in THF (0.32
1.60 mmol) at „78
M
9
9
＝
8.4 Hz, aro-
4.04-4.08 (2H, m, 1-H), 7.34 (2H, d,
matic), 7.79 (2H, d, 8.4 Hz, aromatic). This com-
J
ched with a saturated aqueous NH4Cl solution, and
the mixture was extracted with Et2O. The combined
organic phases were successively washed with water,
a saturated aqueous NH4Cl solution and brine, dried
with MgSO4, and concentrated in vacuo to give a
J
＝
pound was employed in the next step without further
puriˆcation. Its IR spectrum is identical to that in the
literature.12)
mixture of (
±
)-7 and its acetate. To a stirred and ice-
(
±
)-3,7-Dimethylnonyl Iodide [(
±
)-10]. To a so-
-dimethylfor-
mamide (DMF, 30 ml) was added NaI (10.0 g,
66.5 mmol). After stirring at 50 C for 2 h, the mix-
±
lution of crude ( )-9 (4.26 g) in N,N
cooled solution of this mixture in MeOH (50 ml) was
added K2CO3 (3.00 g). After stirring for 30 min at
room temperature, the mixture was poured into
water and extracted with Et2O. The combined organ-
ic phases were successively washed with water and
9
ture was poured into water and extracted with Et2O.
The combined ethereal extracts were successively
washed with a saturated aqueous Na2S2O3 solution,
water and brine, dried with MgSO4, and concentrated
in vacuo. The residue was chromatographed on silica
brine, dried with MgSO4, and concentrated in vacuo
The residue was chromatographed on silica gel (60 g;
hexane AcOEt, 20:1) to give 3.19 g of ( )-7 (63
max (ˆlm) cm„1: 3335
C), 1055 (m, C–O). NMR dH
.
±
z
)
W
as a colorless oil, n2D5 1.4561. IR
(s, O–H), 1645 (m, C
(400 MHz, CDCl3): 0.91 (3H, d,
n
gel (160 g; hexane) to give 3.33 g (2 steps, 95
z) of 10
＝
as a colorless oil, n2D3 1.4808. IR max (ˆlm) cm„1: 1175
n
＝
J
7.0 Hz, 3-Me),
(m, CH2–I). NMR dH (400 MHz, CDCl3): 0.85–0.90
(9H, m, 3-Me, 7-Me, 9-H), 1.04–1.57 (10H, m, 2-H,
4-H, 5-H, 6-H, 8-H), 1.59–1.68 (1H, m, 7-H),
1.82–1.92 (1H, m, 3-H), 3.14-3.28 (2H, m, 1-H).
This compound was employed in the next step
without further puriˆcation.
＝
J
0.98 (3H, t,
7.0 Hz, 9-H), 1.11–1.24 (2H, m,
4-H), 1.26–1.43 (2H, m, 2-H), 1.52–1.67 (2H, m,
3-H, –OH), 1.60 (3H, s, 7-Me), 1.92–2.10 (4H, m,
5-H, 8-H), 3.63-3.71 (2H, m, 1-H), 5.09 (1H, t, J
＝
7.1 Hz, 6-H). The IR and 1H-NMR spectra are identi-
cal to those in the literature.12)
(
±
)-3,7-Dimethyl-6-decen-1-ol [(
±
)-11]. In
a
±
±
±
8
(
)-3,7-Dimethylnonan-1-ol [( )-
]. A solution
of ( )-7 (3.00 g, 17.6 mmol) in 99.5 EtOH
(2.0 ml) was shaken under an H2 atmosphere in the
presence of 10 Pd-C (300 mg) for 24 h at room
similar manner to that described for the preparation
±
M
z
of ( )-7, except that EtMgBr in dry THF (0.94
,
2.60 ml, 2.44 mmol) was employed for this conver-
±
z
sion, ( )-6 (730 mg, 2.85 mmol) yielded 370 mg
(70 ) of (
)-11 as a colorless oil, n2D4 1.4547. IR nmax
(ˆlm) cm„1: 3420 (w, O–H), 1050 (m, C–O). NMR dH
temperature. The catalyst was removed by ˆltration
through a Celite pad, and the ˆltrate was concentrat-
ed in vacuo. The residue was chromatographed on
z
±
＝
(400 MHz, CDCl3): 0.85 (3H, t,
J
7.2 Hz, 10-H)
7.2 Hz, 3-Me), 1.15–1.25 (2H, m,
9-H), 1.30–1.45 (3H, m, 4-H, O–H), 1.57 (3H, seem-
ingly d, 5.1 Hz, 7-Me), 1.61–1.70 (3H, m, 2-H,
＝
0.91 (3H, d, J
silica gel (60 g; hexane AcOEt, 10:1) to give 2.77 g of
W
±
(
)-8 (87
z
n
) as a colorless oil, n2D4 1.4390 (lit.12) n2D0
1.4375). IR
max (ˆlm) cm„1: 3335 (s, O–H), 1055 (m,
J
＝

Syntheses of Two Tetramethylalkanes of the Tsetse Fly
585
±
3-H), 1.90–2.10 (4H, m, 5-H, 8-H), 3.67 (2H, m,
(
)-17 and the corresponding aldehyde. To a stirred
＝
1-H), 5.10 (1H, t,
78.20; H, 13.12
13.32
J
6.4 Hz, 6-H). Anal. Found: C,
and ice-cooled solution of this mixture in THF
(30 ml) and water (30 ml) was added NaBH4 (2.00 g,
52.9 mmol). After stirring for 30 min at 09C, the
z
. Calcd. for C12H24O: C, 77.72; H,
z.
mixture was poured into AcOH and brine, and the
resulting mixture was extracted with AcOEt. The
combined organic phases were successively washed
with a saturated NaHCO3 solution and brine, dried
with MgSO4, and concentrated in vacuo. The residue
was chromatographed on silica gel (250 g; hexane
±
±
)-3,7-Dimethyldecan-1-ol [( )-12]. In the same
(
manner as that described for the preparation of
±
(90
±
±
(
)-8, ( )-11 (1.80 g, 9.80 mmol) yielded 1.60 g
z
) of ( )-12 as a colorless oil, n2D4 1.4426
s
lit.13)
n2D0 1.4430 [(3
R
,7
R
)-12]
t
. IR nmax (ˆlm) cm„1: 3420
W
±
(m, O–H), 1055 (m, C–O). NMR dH (400 MHz,
AcOEt, 9:1) to give 10.2 g of ( )-17 (53
colorless waxy solid, mp 25–30 C. IR nmax (ˆlm)
cm„1: 3325 (s, O–H), 1040 (m, C–O). NMR dH (500
z) as a
＝
CDCl3): 0.84 (3H, d,
J
6.6 Hz, 7-Me), 0.87 (3H, t,
9
＝
＝
J
7.3 Hz, 10-H), 0.89 (3H, d,
J
6.3 Hz, 3-Me),
＝
7.0 Hz, 6-Me), 0.88
1.06–1.39 (12H, m, 3-H, 4-H, 5-H, 6-H, 7-H, 8-H,
9-H), 1.61 (2H, m, 2-H), 3.68 (2H, m, 1-H). IR nmax
(ˆlm) cm„1: 3420 (w, O–H), 2930 (s, C–H), 1460 (m,
C–H). NMR dH (400 MHz, CDCl3): 0.83–0.90 (9H,
m, 3-Me, 7-Me, 10-Me), 1.32 (12H, m, 3-H, 4-H,
5-H, 6-H, 7-H, 8-H, 9-H,), 1.61 (2H, m, 2-H), 3.68
(2H, m, 1-H).
MHz, CDCl3): 0.86 (3H, d,
J
(3H, t, 7.0 Hz, 22-H), 1.23–1.37 (34H, m, 5-H,
J
＝
6-H, 7-H, 8-H, 9-H, 10-H, 11-H, 12-H, 13-H, 14-H,
15-H, 16-H, 17-H, 18-H, 19-H, 20-H, 21-H, –OH),
1.67 (3H, s, 2-Me), 2.06 (2H, m, 4-H), 3.99(2H, s,
1-H), 5.40 (1H, m, 3-H). Anal. Found: C, 81.41; H,
13.77
z z
. Calcd. for C24H48O: C, 81.74; H, 13.72 .
±
±
± ±
)-2,6-Dimethyldocosan-1-ol [( )-18]. A solu-
(
)-3,7-Dimethyldecyl Tosylate [( )-13]. In the
(
±
same manner as that described for the preparation of
tion of ( )-17 (2.90 g, 8.63 mmol) in 99.5
z
EtOH
(5 ml) was shaken in an H2 (3–4 kg cm2) atmosphere
±
±
±
(
)-9, ( )-12 (1.30 g, 6.98 mmol) yielded 3.05 g of
crude (
)-13 as a colorless oil, n2D3 1.4983. IR nmax
(ˆlm) cm„1: 1360 (s, SO2), 1180 (s, SO2). NMR dH
W
in the presence of Raney nickel (W 7; 500 mg) for 18
h at room temperature. The catalyst was removed by
ˆltration through a Celite pad, and the ˆltrate was
concentrated in vacuo. The residue was chro-
＝
(500 MHz, CDCl3): 0.80 (3H, d, 6.8 Hz, 7-Me),
J
0.83 (3H, t, 6.7 Hz, 10-H), 0.88 (3H, d, J 7.0
J
＝ ＝
Hz, 3-Me), 1.19–1.26 (14H, m, 2-H, 3-H, 4-H, 5-H,
matographed on silica gel (55 g; hexane AcOEt,
W
6-H, 7-H, 8-H, 9-H), 2.45 (3H, s, Ar-Me), 4.07 (2H,
50:1) to give 2.92 g of (
±
)-18 (quant.) as a colorless
max (ˆlm) cm„1: 3395 (s,
＝
m, 1-H), 7.34 (2H, d,
(2H, d,
J
8.0 Hz, aromatic), 7.79
8.2 Hz, aromatic). This compound was
waxy solid, mp 25–30 C. IR n
9
＝
J
O–H), 1010 (m, C–O). NMR dH (400 MHz, CDCl3):
0.83–0.93 (9H, m, 2-Me, 6-Me, 22-H), 1.08–1.43
(37H, m, 3-H, 4-H, 5-H, 6-H, 7-H, 8-H, 9-H, 10-H,
11-H, 12-H, 13-H, 14-H, 15-H, 16-H, 17-H, 18-H,
19-H, 20-H, 21-H, –OH), 1.55–1.61 (2H, m, 2-H),
3.39-3.52 (2H, m, 1-H). Anal. Found: C, 81.17; H,
employed in the next step without further puriˆca-
tion.
±
±
)-3,7-Dimethyldecyl Iodide [( )-14]. In the
(
same manner as that described for the preparation of
(
87
±
)-10, crude (
±
)-13 (2.98 g) yielded 1.80 g (2 steps,
lit.13) n2D0
. IR nmax (ˆlm) cm„1: 1170 (m,
z z
14.49 . Calcd. for C24H50O: C, 81.28; H, 14.21 .
) of ( )-14 as a colorless oil, n2D4 1.4817
s
±
z
1.4849 [(3
R
,7
R
)-14]
t
(
±
)-2,6-Dimethyldocosyl Tosylate [(
±
)-19]. In the
CH2–I). NMR dH (500 MHz, CDCl3): 0.84 (3H, d,
same manner as that described for the preparation of
＝
＝
± ±
)-9, ( )-18 (500 mg, 0.99 mmol) yielded 464 mg
J
6.6 Hz, 7-Me), 0.86 (3H, t,
J
5.8 Hz, 10-H),
(
0.88 (3H, d, 6.4 Hz, 3-Me), 1.26–1.32 (14H, m,
J
＝
(93
z
) of (
±
)-19 as a colorless oil, n2D5 1.4806. IR nmax
(ˆlm) cm„1: 1600 (m, aromatic), 1365 (m, S O),
＝
2-H, 3-H, 4-H, 5-H, 6-H, 7-H, 8-H, 9-H), 3.22 (2H,
m, 1-H).
1180 (m, S–O–C). NMR dH (400 MHz, CDCl3): 0.80
＝
6.8 Hz, 6-Me), 0.86–0.94 (6H, m, 2-Me,
(3H, d,
J
±
±
(
)-(E)-2,6-Dimethyl-2-docosen-1-ol [( )-17]. To
22-H), 0.95–1.34 (38H, m, 2-H, 3-H, 4-H, 5-H, 6-H,
7-H, 8-H, 9-H, 10-H, 11-H, 12-H, 13-H, 14-H, 15-H,
16-H, 17-H, 18-H, 19-H, 20-H, 21-H), 2.45 (3H, s,
a stirred and ice-cooled mixture of SeO2 (824 mg,
7.43 mmol) and tert-butyl hydroperoxide (2.70 ml,
30.0 mmol) in CH2Cl2 (5 ml) was added a solution of
)-16 (10.0 g, 30.0 mmol) in CH2Cl2 (50 ml). After
stirring for 2 h at room temperature, the mixture was
poured into a 10 aqueous Na2SO3 solution. The
＝
J
Ar-Me), 3.78–3.89 (2H, m, 1-H), 7.53 (2H, d,
±
＝
(
8.4 Hz, aromatic), 7.79 (2H, d,
ic). Anal. Found: C, 72.89; H, 11.36
C31H56O3S: C, 73.17; H, 11.09
J
8.4 Hz, aromat-
z
. Calcd. for
z
z
.
mixture was stirred at room temperature for 1 h and
extracted with Et2O. The combined ethereal extracts
±
±
(
)-2,6-Dimethyldocosyl Iodide [( )-20]. In the
were successively washed with a 10
z
aqueous
same manner as that described for the preparation of
±
(82
±
Na2SO3 solution, water and brine, dried with MgSO4,
and concentrated in vacuo to give a mixture of
(
)-10, ( )-19 (250 mg, 0.50 mmol) yielded 191 mg
z
) of (
±
)-20 as a colorless oil, n2D5 1.4377. IR nmax

586
C. SHIBATA et al.
(ˆlm) cm„1: 1195 (m, CH2–I). NMR dH (300 MHz,
J
7.8 Hz, aromatic). Anal. Found: C, 77.94; H,
＝
12.24
12.10
CDCl3): 0.84–0.96 (6H, m, 6-Me, 22-H), 0.98 (3H, d,
z
.
.
Calcd. for C41H76O2S: C, 77.78; H,
＝
J
6.2 Hz, 2-Me), 1.19–1.37 (38H, m, 2-H, 3-H,
z
4-H, 5-H, 6-H, 7-H, 8-H, 9-H, 10-H, 11-H, 12-H,
13-H, 14-H, 15-H, 16-H, 17-H, 18-H, 19-H, 20-H,
21-H), 3.13-3.26 (2H, m, 1-H). Anal. Found: C,
4,8,12,16-Tetramethyl-11-phenylsulfonyldotria-
±
contane [( )-23]. In a similar manner to that
±
described for the preparation of ( )-22, except that
62.08; H, 10.86
10.63
z. Calcd. for C24H49 I: C, 62.05; H,
±
)-14 (627 mg, 2.12 mmol) was employed for this
z
.
(
±
conversion, ( )-21 (676 mg, 1.41 mmol) yielded 781
(
±
) - 2,6 - Dimethyl - 1 - phenylsulfonyldocosane
z
mg (85 ) of (
±
)-23 as a colorless oil, n2D4 1.4848. IR
[( )-21]. To a stirred solution of ( )-20 (2.65 g,
nmax (ˆlm) cm„1: 1310 (s, SO2), 1150 (s, SO2). NMR
dH (400 MHz, CDCl3): 0.79–0.89 (18H, m, 2-Me,
4-Me, 8-Me, 12-Me, 16-Me, 32-H), 1.21–1.25 (54H,
m, 2-H, 3-H, 4-H, 5-H, 6-H, 7-H, 9-H, 10-H, 11-H,
12-H, 13-H, 14-H, 15-H, 16-H, 17-H, 18-H, 19-H,
20-H, 21-H, 22-H, 23-H, 24-H, 25-H, 26-H, 27-H,
28-H, 29-H, 30-H, 31-H) 2.88 (1 H, m, 11-H), 7.57
±
±
・
10.4 mmol) in DMF (50 ml) was added NaSO2Ph
2H2O (2.37 g, 14.4 mmol). The mixture was stirred at
room temperature for 12 h, poured into brine, and
extracted with Et2O. The combined ethereal extracts
were successively washed with water and brine, dried
with MgSO4, and concentrated in vacuo. The residue
＝
＝
7.3 Hz,
was chromatographed on silica gel (60 g; hexane
(3H, t,
aromatic). Anal. Found: C, 78.02; H, 12.23
Calcd. for C42 H78O2S; C, 77.95; H, 12.15; O, 4.94;
S, 4.96
J
8.0 Hz, aromatic) 7.89 (2H, d,
J
W
±
AcOEt, 20:1) to give 2.48 g (79
colorless oil, nD25 1.4889. IR max (ˆlm) cm„1: 1585 (m,
aromatic), 1305 (s, SO2), 1150 (s, SO2). NMR dH
z
) of ( )-21 as a
z.
n
z
＝
6.6 Hz, 6-Me),
(300 MHz, CDCl3): 0.81 (3H, d,
J
＝
＝
±
1
0.88 (3H, t,
J
6.6 Hz, 22-H), 1.07 (3H, d,
J
3,7,11,15 - Tetramethylhentriacontane
[( )- ].
6.6 Hz, 2-Me), 1.14–1.37 (38H, m, 2-H, 3-H, 4-H,
5-H, 6-H, 7-H, 8-H, 9-H, 10-H, 11-H, 12-H, 13-H,
14-H, 15-H, 16-H, 17-H, 18-H, 19-H, 20-H, 21-H),
Lithium wire (145 mg, 20.9 mmol) was dissolved in
9
EtNH2 (10 ml) at „50 C under argon. To the stirred
±
and cooled solution of lithium, a solution of ( )-22
＝
2.89–3.11 (2H, m, 1-H), 7.56 (2H, t,
matic), 7.63 (1H, t, 7.7 Hz, aromatic), 7.92 (2H,
7.7 Hz, aromatic). Anal. Found: C, 74.98; H,
J
7.7 Hz, aro-
(150 mg, 0.24 mmol) in dry THF (1.5 ml) was added
J
＝
9 9
dropwise at „60 C. After stirring at º„50 C for
＝
z
d,
J
2 h, the reaction was quenched with NH4Cl. After
removing EtNH2, the mixture was poured into a satu-
rated aqueous NH4Cl solution and extracted with
hexane. The combined organic phases were washed
with water and brine, dried with MgSO4, and concen-
trated in vacuo. The residue was chromatographed
11.64
11.37
.
.
Calcd. for C30H54O2S: C, 75.25; H,
z
(
±
)-3,7,11,15-Tetramethyl-10-phenylsulfonylhen-
±
triacontane [( )-22]. To a stirred and cooled solu-
tion of ( )-21 (300 mg, 0.63 mmol) in dry THF
(5 ml) and dry hexamethylphosphoramide (HMPA,
3 ml) was added -BuLi in hexane (1.56 , 0.70 ml,
1.09 mmol) at „78 C under argon. The solution was
stirred at „50 C for 15 min and then cooled to
„78 C. A solution of ( )-10 (200 mg, 0.71 mmol)
in dry THF (3 ml) was added dropwise to the mixture
at „78 C while stirring. The mixture was stirred at
C for 4 h, poured into a saturated aqueous NH4Cl
solution at 0 C, and extracted with Et2O. The com-
±
on silica gel (4 g; hexane) to give 97.2 mg (83
) of
z
±
(
)-1 as a colorless oil, n2D5 1.4562. IR nmax (ˆlm)
n
M
cm„1: 2925 (s, C–H), 2855 (s, C–H), 1465 (m, CH2),
1375 (m, CH2). NMR dH (500 MHz, CDCl3):
0.72–0.87 (18H, m, 1-H, 3-Me, 7-Me, 11-Me, 15-Me,
31-H), 0.89–1.36 (54H, m, 2-H, 3-H, 4-H, 5-H, 6-H,
7-H, 8-H, 9-H, 10-H, 11-H, 12-H, 13-H, 14-H, 15-H,
16-H, 17-H, 18-H, 19-H, 20-H, 21-H, 22-H, 23-H,
24-H, 25-H, 26-H, 27-H, 28-H, 29-H, 30-H). MS
9
9
±
9
9
0
9
9
(EI) m z (relative intensity): 56.9 (94), 70.9 (100),
W
bined ethereal extracts were successively washed with
water and brine, dried with MgSO4, and concentrated
in vacuo. The residue was chromatographed on silica
126.9 (86), 195.8 (61), 196.8(80), 266.7(61), 321.7
(63), 322,7 (81), 392.7 (71), 448.6 (14), 462.6 (31),
476.6 (23), 491.5 (M+, 16). GC [NB-5} column
gel (8 g; hexane AcOEt, 50:1) to give 400 mg (99
z
max (ˆlm)
)
(0.25 mm
×
30 m), 60+28
9
C min to 180
9
C, and
W
W
of ( )-22 as a colorless oil, n2D5 1.4854. IR
n
180+3.09C min to 3209C; He carrier gas at
±
W
cm„1: 1590 (w, aromatic), 1305 (s, SO2), 1150 (s,
SO2). NMR dH (500 MHz, CDCl3): 0.73–1.09
(18H,m, 1-H, 3-Me, 7-Me, 11-Me, 15-Me, 31-H),
1.11–1.31 (52H, m, 2-H, 3-H, 4-H, 5-H, 6-H, 7-H,
8-H, 9-H, 11-H, 12-H, 13-H, 14-H, 15-H, 16-H,
17-H, 18-H, 19-H, 20-H, 21-H, 22-H, 23-H, 24-H,
25-H, 26-H, 27-H, 28-H, 29-H, 30-H), 2.87–2.88
＝
1.0 kg cm2] tR 52.2 min (1,
À
98z
chemical puri-
. Calcd. for
＝
W
ty). Anal. Found: C, 85.08; H, 15.05
z
C35H72: C, 85.28; H, 14.72
z.
±
4,8,12,16-Tetramethyldotriacontane [( )-
2]. In
the same manner as that described for the prepara-
±
±
tion of ( )-1, ( )-23 (720 mg, 1.11 mmol) yielded
(1H, m, 10-H), 7.56 (2H, t,
J
7.8 Hz, aromatic),
456 mg (81
) of ( )-2 as a colorless oil, nD25
± ＝
z
7.63 (1H, t,
J 7.8 Hz, aromatic), 7.89 (2H, d,
＝
1.4767. IR nmax (ˆlm) cm„1: 2920 (s, C–H), 1460 (m,

Syntheses of Two Tetramethylalkanes of the Tsetse Fly
587
tachinoides. Biosci. Biotechnol. Biochem.
,
58,
CH2), 720 (m, CH2). NMR dH (400 MHz, CDCl3):
539–543 (1994).
0.83–0.89 (18H, m, 1-H, 4-Me, 6-Me, 8-Me, 12-Me,
32-H), 1.21–1.25 (56 H, m, 2-H, 3-H, 4-H, 5-H, 6-H,
7-H, 8-H, 9-H, 10-H, 11-H, 12-H, 13-H, 14-H, 15-H,
16-H, 17-H, 18-H, 19-H, 20-H, 21-H, 22-H, 23-H,
24-H, 25-H, 26-H, 27-H, 28-H, 29-H, 30-H, 31-H).
5) Kimura, T., Carlson, D. A., and Mori, K.,
Pheromone synthesis, Part 211. Synthesis of all the
stereoisomers of 13,17-dimethyl-1-tritriacontene and
13,17-dimethyl-1-pentatriacontene, the contact sex
pheromone components of the female tsetse ‰y, Glos-
sina austeni. Eur. J. Org. Chem., 3385–3390 (2001).
6) Nelson, D. R., Carlson, D. A., and Fatland, C. L.,
Cuticular hydrocarbons of tsetse ‰ies II: Glossina fus-
cipes fuscipes, G. palpalis palpalis, G. p. gambiensis,
G. tachinoides, and G. berevipalpis. J. Chem. Ecol.
14, 963–987 (1988).
7) Mori, K., Organic synthesis and chemical ecology.
Acc. Chem. Res., 33, 102–110 (2000).
MS (EI) m z (relative intensity): 71 (18.4), 141 (18.2),
W
211 (17.0), 252 (14.0), 281(11.0), 323 (19.2), 393
(17.1), 463 (9.0), 491 (5.1), 506 (M+, 4.6). Anal.
Found: C, 85.29; H, 14.71
z
. Calcd. for C36H74: C,
. GC [TC–WAX column (0.2 mm
30 m), 60 to 180 C, +28 C min, 180 to 320 C,
+3
C min; He carrier gas at 1.0 kg cm2] tR
54.0 min (2,
85.25; H, 14.87
z
,
×
9
9
9
＝
W
9
W
W
À
98z chemical purity).
8) Carlson, D. A., OŠer, I. I., El Messoussi, S.,
Matsuyama, K., Mori, K., and Jallon, J.-M., Sex
Acknowledgment
pheromone of Glossina tachinoides
:
Isolation,
identiˆcation, and synthesis. J. Chem. Ecol., 24,
1563–1575 (1998).
9) Eschinasi, E. H., A new synthesis of rosoxide. J. Org.
Chem., 35, 1097–1100 (1970).
We thank Dr. David A. Carlson (U.S. Department
of Agriculture) for discussions. Financial support for
this work from Mitsubishi Gas Chemical Co. and
Nitto Denko Co. is acknowledged with thanks.
10) Kefalas, P. and Ragousis, N., E‹cient synthesis of
the Aonidiella aurantii (Mask.) sex pheromone com-
ponent:
(3S,6RS)-3-methyl-6-(1-methylethenyl)-9-
References
decenyl acetate. Synthesis, 644–646 (1995).
11) Fouquet, C. and Schlosser, M., Improved carbon-
carbon linking by controlled copper catalysis. Angew.
Chem. Int. Ed. Engl., 13, 82–83 (1974).
1) Carlson, D. A., Langley, P. A., and Huyton, P. M.,
Sex pheromone of the tsetse ‰y: Isolation, identiˆca-
tion and synthesis of contact aphrodisiacs. Science
201, 750–753 (1978).
,
12) Mori, K., Kuwahara, S. and Ueda, H., Pheromone
synthesis, Part 55. Synthesis of all of the four possible
stereoisomers of 4,8-dimethyldecanal, the aggrega-
tion pheromone of the ‰our beetles. Tetrahedron, 39,
2439–2444 (1983).
13) Mori, K. and Murata, N., Pheromone synthesis, Part
167. Synthesis of all of the eight stereoisomers of
methyl 2,6,10-trimethyltridecanoate, the male-
produced pheromone of the stink bugs, Euschistus
2) Hoshino, C. and Mori, K., Pheromone synthesis,
Part 40. Synthesis of a diastereomeric mixture of
15,19,23-trimethylheptatriacontane, the most active
component of the sex pheromone of the female tsetse
‰y, Glossina morsitans morsitans. Agric. Biol.
Chem., 44, 3007–3009 (1980).
3) Kuwahara, S. and Mori, K., Pheromone synthesis,
Part 62. Synthesis of all of the three possible
stereoisomers of 13,23-dimethylpentatriacontane, a
sex pheromone of the tsetse ‰y, Glossina pallidipes.
Agric. Biol. Chem., 47, 2599–2606 (1983).
heros and E. obscurus. Liebigs Ann. Chem.
,
1153–1160 (1994).
14) Takikawa, H., Fujita, K., and Mori, K., Pheromone
4) Matsuyama, K. and Mori, K., Pheromone synthesis,
Part 159. Synthesis of a stereoisomeric mixture of
13,25-, 11,21- and 11,23-dimethylheptatriacontane,
the contact sex pheromone of the tsetse ‰y, Glossina
synthesis, Part 180. Synthesis of (3S,11S)-3,11-
dimethyl-2-heptacosanone, a new component of the
female sex pheromone of the German cockroach.
Liebigs Ann. Recueil, 815–820 (1997).
W