2
6
N.M. Carballeira, M. Pag a´ n / Chemistry and Physics of Lipids 113 (2001) 23–27
were refluxed for 24 h. After this time the solvent
was removed in vacuo and the product, a viscous
oil, was purified by silica gel column chromatogra-
phy using n-hexane/diethyl ether (9:1) as the eluent.
Yield was 99% of a 9:1 mixture (as determined by
capillary GC) of Z/E isomers. The spectral data for
the Z isomer is presented below. IR (neat) n 3007
D8 double bond, and commercially available 8-
methylnonanoic acid to introduce the iso branching
(Scheme 1). This approach is general, and can be
used to generate other biosynthetically related
monounsaturated iso fatty acids, such as the 14-
methyl-6(Z)-pentadecenoic acid (Stefanov et al.,
1992), by just changing the length of the Wittig salt.
Therefore, our synthesis started with 8-methyl-
nonanoic acid, which was converted to 8-methyl-1-
nonanol through the lithium aluminum hydride
reduction of the corresponding methyl ester. This
turned out to be a convenient way to generate
methylnonanol with a combined overall yield of
94% for the two steps. A previous reported synthe-
sis for 8-methyl-1-nonanol utilized as starting ma-
terial hexane-1,6-diol which was monobrominated
with hydrobromic acid (70% yield) and then pro-
tected as the pyranyloxy bromide with dihydropy-
ran upon acid catalysis (Hassarajani et al., 1995).
This reaction was followed by Grignard coupling
with isobutylmagnesium bromide in the presence of
Li CuCl as catalyst to generate the dihydropyranyl
(
=CH, olefinic), 2954, 2926, 2857, 1744 (C=O),
−
1 1
1
465, 1384, 1366, 1171, 1020, 726 cm ; H NMR
l 5.33 (2H, m, 8-H, 9-H), 3.65 (3H, s, -OCH ), 2.29
3
(
2H, t, J=7.5 Hz, 2-H), 2.00 (4H, m, 7-H, 10-H),
.62 (2H, m, 3-H), 1.50 (1H, m, 16-H), 1.30 (12H,
brs, CH ), 1.25 (2H, m, 14-H), 1.15 (2H, m, 15-H),
1
2
13
0
(
.85 (6H, d, J=6.6 Hz, 17-H, Me-16); C NMR
75 MHz) l 174.3 (s, C-1), 130.1 (d, C-9), 129.6 (d,
C-8), 51.4 (q, -OCH ), 39.0 (t, C-15), 34.0 (t, C-2),
3
2
2
9.8 (t), 29.7 (t), 29.5 (t), 29.3 (t), 29.0 (t), 28.9 (t),
7.9 (d, C-16), 27.4 (t, C-14), 27.1 (t, C-10), 27.0 (t,
C-7), 24.9 (t, C-3), 22.6 (q, C-17), 22.5 (q, Me-16);
GC-MS, ECL=17.33, (70 eV) m/z (relative inten-
+
sity) 296 (M , 3), 265 (11), 264 (15), 241 (6), 222
2
4
(
(
(
(
9), 180 (5), 141 (6), 138 (5), 137 (8), 125 (8), 124
8), 123 (14), 115 (6), 112 (6), 111 (17), 110 (16), 109
16), 101 (6), 98 (27), 97 (37), 96 (32), 95 (25), 94
5), 93 (5), 87 (37), 85 (11), 84 (36), 83 (42), 82 (22),
protected 8-methyl-1-nonanol (58% yield) which
upon deprotection with acid resulted in the desired
8
-methylnonanol. The overall yield for this re-
ported four-step sequence was less than 40%.
Therefore, the two-step sequence we are employing
here (acid ester alcohol) for the synthesis of
81 (33), 79 (12), 75 (8), 74 (56), 73 (6), 71 (13), 70
(
(
15), 69 (72), 68 (24), 67 (46), 59 (24), 57 (40), 56
37), 55 (100), 54 (25); HRMS calcd for C H O
2
1
9
36
8
-methyl-1-nonanol is definitely more efficient pro-
m/z 296.2715, found 296.2714.
vided that the starting methylnonanoic acid is
available. In the next step of our synthesis the
2.8. Methyl 16-methyl-8(E)-heptadecenoate
8
-methyl-1-nonanol was transformed into 8-
methylnonanal, required for the Wittig coupling,
upon reaction with pyridinium chlorochromate in
dichloromethane, resulting in a 98% isolated yield
of the aldehyde. We should mention that 8-methyl-
nonanal is also a volatile natural product, previ-
ously identified in rabbit and peel oils (Goodrich,
et al., 1978; Tajima et al., 1990), and decomposes
readily if it is not handled expeditiously. Final
Wittig coupling of 8-methylnonanal with 7-car-
boxyheptyltriphenylphosphonium bromide (pre-
pared from 8-bromooctanoic acid as described in
Section 2) resulted in a 9:1 mixture (as determined
by capillary GC of the methyl ester) of 16-methyl-
8(Z)-heptadecenoic acid (1Z) and 16-methyl-8(E)-
heptadecenoic acid (1E) which to gether accounted
for a 24% isolated yield (22% overall yield from
8-methylnonanoic acid).
GC-MS, ECL=17.38, (70 eV) m/z (relative
intensity) 296 (M , 3), 265 (9), 264 (13), 241 (6),
+
2
1
1
9
(
7
22 (8), 180 (5), 152 (5), 141 (7), 138 (5), 137 (6),
25 (8), 124 (7), 123 (13), 115 (6), 112 (5), 111 (16),
10 (17), 109 (16), 107 (5), 101 (6), 99 (6), 98 (24),
7 (37), 96 (32), 95 (24), 94 (5), 93 (6), 87 (39), 85
12), 84 (36), 83 (41), 82 (21), 81 (31), 80 (5), 79 (12),
7 (5), 75 (8), 74 (59), 73 (7), 71 (17), 70 (15), 69
80), 68 (25), 67 (49), 65 (6), 59 (19), 57 (43), 56 (35),
(
5
5 (100), 54 (31).
3
. Results and discussion
The synthesis of 16-methyl-8-heptadecenoic acid
1) was based on Wittig coupling to generate the
(