2232 J . Org. Chem., Vol. 67, No. 7, 2002
Rodr´ıguez et al.
12-Tr id ecyn -2-ol (6).41 To a solution of aldehyde 5 (2.54 g,
14.0 mmol) in dry THF (6 mL) kept at -50 °C was added,
under argon, 5.6 mL (17 mmol) of a 3 M solution of MeMgBr
in Et2O. The mixture was stirred at -50 °C for 10 min and
warmed to 0 °C; to the mixture was added 1 N HCl until
complete solubilization of the crude, and the product was
extracted with ethyl acetate. The combined organic layers were
washed with brine and dried, and the crude product resulting
from evaporation of the solvent was purified by column
chromatography (hexane/Et2O 80:20) to afford 2.06 g (10.5
mmol, 75%) of alcohol 6: 1H NMR δ 3.75 (c, 1H), 2.15 (dt, J )
2.5, 7.0 Hz, 2H), 1.91 (t, J ) 2.5 Hz, 1H), 1.49 (m, 2H), 1.26
(b, 14H), 1,15 (d, J ) 6.5 Hz, 3H); 13C NMR δ 84.7, 68.1, 68.0,
39.3, 29.5, 29.3, 29.0, 28.7, 28.4, 25.7, 18.3, 23.4; IR 3388, 3315,
(R)-(-)-12-Tr id ecyn -2-ol (R-6). A mixture of acetate (R)-7
(486 mg, 2.0 mmol), K2CO3 (1.1 g, 8.1 mmol), and methanol (9
mL) was stirred at room temperature for 3 h. The mixture was
cooled at 0 °C, and 1 M HCl was added until complete
solubilization of the suspension was achieved. Methanol was
evaporated, and the product was extracted with ethyl acetate.
The reaction crude was purified by column chromatography
using hexane/Et2O (80:20) to obtain the expected alcohol (R)-6
(377 mg, 1.9 mmol, 95%): 1H NMR δ 3.77 (c, 1H), 2.15 (dt, J
) 2.5, 7.0 Hz, 2H), 1.91 (t, J ) 2.5 Hz, 1H), 1.49 (m, 2H), 1.26
(b, 14H), 1.16 (d, J ) 6.5 Hz, 3H); 19F NMR δ -71.945 (8%,
(S)-enantiomer), -71.989 (92% (R)-enantiomer); [R]20 -5 (c
D
5, CHCl3); ee 84%.
12-Tr id ecyn -2-yl Meth a n esu lfon a te (8). Compound 8
was obtained from 6 following a previously reported proce-
dure.34 S-(+)-8: yield 82% (437 mg, 1.6 mmol) after column
chromatography (hexane/Et2O (80:20)); 1H NMR δ 4.76 (tq, J
) 6.0, 6.5 Hz, 1H), 2.96 (s, 3H), 2.15 (dt, J ) 2.5, 7.0 Hz, 2H),
1.91 (t, J ) 2.5 Hz, 1H), 1.38 (d, J ) 6.0 Hz, 3H), 1.25 (b, 16H);
13C NMR δ 84.7, 80.4, 68.0, 38.6, 36.6, 29.3, 29.1, 28.9, 28.6,
28.4, 25.1, 18.3, 21.3; IR 3291, 2931, 2856, 1464, 1352, 1176,
2929, 2902, 2860, 1466, 1378, 1133 cm-1
.
Mosh er Ester s P r ep a r a tion . Oxalyl chloride (16 µL, 0.18
mmol) was added to a mixture of (S)-(-)-methoxytrifluoro-
methylacetic acid (8 mg, 0.03 mmol) and DMF (8 µL, 0.1210
mmol) in dry hexane (1 mL) under argon at room temperature.
After 2 h, the formed precipitate was filtered off and solvent
was evaporated to dryness at reduced pressure. This residue
was dissolved in 0.350 mL of dry CH2Cl2 and added to a
mixture of the nonracemic alcohol 6 (5 mg, 0.025 mmol), dry
Et3N (10 µL, 0.14 mmol), and DMAP (catalytic amount). After
2 h of stirring at room temperature, the solvent was removed
under vacuum and CDCl3 was added: (S)-6-MTPA, 19F NMR
δ -71.945; (R)-6-MTPA, 19F NMR δ -71.989.
En zym e Dep osition a n d Ad sor p tion . The general pro-
cedure for the deposition of the enzymes onto solid support
materials was the following. An enzyme solution in 50 mM
aqueous phosphate buffer pH 7.0 (1 mL) was mixed thoroughly
with the support (1 g). The mixture was then evaporated under
vacuum overnight. For A. niger (ANL), Pseudomonas sp. (PSL),
C. rugosa lipase (CRL), and PPL, the enzyme loading was 100
mg of enzyme/g of Celite. Adsorption onto polypropylene was
carried out following the methodology described by Gitlesen
et al.42 C. antarctica and R. miehei lipases were supplied as
immobilized preparations on a macroporous acrylic resin and
a macroporous anion exhange resin, respectively.
971, 915 cm-1; [R]20 +6 (c 5, CHCl3). R-(-)-8: yield 81% (418
D
mg, 1.5 mmol); [R]20 -6 (c 5, CHCl3).
D
[12-2H]-1-Tr id ecyn e (9). Compound 9 was obtained from
7 following a previously reported procedure.34 (R)-9: yield 78%
(211 mg, 1.2 mmol) after column chromatography (hexane);
1H NMR δ 2.16 (dt, J ) 2.5, 7.0 Hz, 2H), 1.91 (t, J ) 2.5 Hz,
1H), 1.23 (b, 17H), 0.84 (d, J ) 5.5 Hz, 3H); 13C NMR δ 84.7,
67.9, 31.8, 29.6, 29.5, 29.3, 29.1, 28.7, 28.4, 25.1, 18.3, 22.28
(t, J ) 19.0 Hz), 13.9; IR 3315, 2926, 2854, 1458, 1238 cm-1
.
Anal. Calcd for C13H23D: C, 86.11; H + D, 13.34. Found: C,
85.78; H + D, 13.21. (S)-9: yield 70% (193 mg, 1.1 mmol). Anal.
Calcd for C13H23D: C, 86.11; H + D, 13.34. Found: C, 85.69;
H + D, 13.54.
[13-2H]-Meth yl 2-Tetr a d ecyn oa te (10). Compound 10
was obtained from 9 following a previously reported proce-
dure34 and purified by column chromatography (hexane/Et2O
(97:3)). (S)-10: yield 83% (206 mg, 0.86 mmol); 1H NMR δ 3.73
(s, 3H), 2.29 (t, J ) 7.0 Hz, 2H), 1.54 (m, 2H), 1.22 (b, 15H),
0.84 (d, J ) 6.0 Hz, 3H); 13C NMR δ 154.28, 89.9, 72.7, 52.5,
31.7, 29.5, 29.3, 29.2, 28.9, 28.7, 27.4, 18.6, 22, 25 (t, J ) 19.0
Kin etic Resolu tion of 6. Reactions at the analytical level
were performed in a 10 mL closed flask. Unless otherwise
stated, vinyl acetate (18 µL, 0.19 mmol) and the racemic
alcohol 6 (25 mg, 0.12 mmol) were dissolved in diisopropyl
ether (1.25 mL). To this solution was added free or immobilized
lipase (Table 1). The mixture was placed on a reciprocal shaker
(125 rpm) thermostated at 25 °C.
Hz), 13.9 (CH3); IR 2924, 2855, 2238, 1722, 1254, 1077 cm-1
.
Anal. Calcd for C15H25DO2: C, 75.26; H + D, 10.94. Found:
C, 74.98; H + D, 11.22. (R)-10: yield 70% (188 mg, 0.78 mmol).
Anal. Calcd for C15H25DO2: C, 75.26; H + D, 10.94. Found:
C, 74.80; H + D, 11.06.
[1,1,1-2H3]-Meth yl [2,2,3,3,13-2H5]-Tetr a d eca n oa te (11).
Compound 11 was obtained from 10 following a previously
reported procedure.34 (S)-11: yield 67% (139 mg, 0.55 mmol)
Reactions at the preparative level were performed as follows.
Vinyl acetate (0.7 mL, 7.5 mmol) and the racemic alcohol 6
(0.99 g, 5.0 mmol) were dissolved in diisopropyl ether (50 mL).
To this solution was added PPL adsorbed on EP100 (2 g). The
mixture was placed on a reciprocal shaker (125 rpm) at 25 °C
for 26 h. The suspension was filtered, and the solid was washed
with Et2O; the solvent was evaporated under vacuum, and the
residue was purified by column chromatography on silica.
Elution with hexane/Et2O (94:6) afforded (R)-(-)-1-methyl-11-
dodecinyl acetate ((R)-7) (486 mg, 2.0 mmol), and elution with
hexane/Et2O (80:20) gave (S)-(+)-12-tridecyn-2-ol ((S)-6) (385
mg, 1.9 mmol). (S)-6: 1H NMR δ 3.76 (c, 1H), 2.15 (dt, J ) 2.5,
7.0 Hz, 2H), 1.91 (t, J ) 2.5 Hz, 1H), 1.26 (b, 16H), 1.15 (d, J
1
after column chromatography (hexane/Et2O (97:3)); H NMR
δ 1.23 (b, 19H), 0.84 (d, J ) 5.5 Hz, 3H); IR 2924, 2854, 1739,
1456, 1283, 1089 cm-1. (R)-11: yield 56% (109 mg, 0.44 mmol).
[2,2,3,3,13-2H5]-Tetr a d eca n oic Acid (1). Compound 1 was
obtained by saponification of 10 following a previously reported
procedure.34 (S)-1: yield 84% (79 mg, 0.34 mmol) after column
chromatography (CH2Cl2/MeOH (98:2)); mp 51-53 °C; 1H
NMR δ 1.23 (b, 19H), 0.85 (d, J ) 5.5 Hz, 3H); 13C NMR δ
180.5, 31.8, 29.66, 29.63, 29.5, 29.4, 29.3, 29.1, 28.7, 33.3
(quintet, J ) 20.0 Hz), 23.83 (quintet, J ) 21.0 Hz), 22.28 (t,
J ) 19.0 Hz), 13.9. IR 2952, 2917, 2850, 1696, 1310, 952 cm-1
.
Anal. Calcd for C14H23D5O2: C, 72.06; H + D, 12.09. Found:
C, 72.40; H, 12.48. (R)-1: yield 87% (88 mg, 0.38 mmol); mp
51-53 °C. Anal. Calcd for C14H23D5O2: C, 72.06; H + D, 12.09.
Found: C, 72.25; H, 12.38.
) 6,5 Hz, 3H); 19F NMR δ -71.945 (>95% (S)-enantiomer);
1
[R]20 +4 (c 5, CHCl3); ee > 95%. (R)-7: H NMR δ 4,85 (tq, J
D
) 6.0, 6.5 Hz, 1H), 2.15 (dt, J ) 2.5, 7.0 Hz, 2H), 1.99 (s, 3H),
1.91 (t, J ) 2.5 Hz, 1H), 1.24 (b, 16H), 1.16 (d, J ) 6.5 Hz,
3H); 13C NMR δ 170.7, 84.7, 71.0, 68.0, 35.8, 29.4, 29.38, 29.36,
29.0, 28.6, 28.4, 25.3, 18.3, 21.3, 19.9; IR 3301, 2978, 2931,
The following are the final deuterium contents (%) of the
labeled substrates, as determined by GC-MS analysis of their
2
2
2
respective methyl esters: (R)-1, 90.4 H5, 8.3 H4, 1.3 H3; (S)-
2857, 1737, 1369, 1244 cm-1; [R]20 -1 (c 5, CHCl3); ee 84%.
1, 89.9 2H5, 7.4 2H4, 2.8 2H3.
D
Bioch em ica l Exp er im en ts. The procedure of Abad et al.18
was followed. Pheromone glands were treated with the probes
dissolved in dimethyl sulfoxide (0.1 µL, 10 µg/µL). A total dose
of 4 µg was given in four subsequent 60 min incubations with
1 µg each. After each treatment, incubations were performed
in chambers at 25 °C and 65% humidity. The glands were
dissected 60 min after the last application, and tissues were
Anal. Calcd for C15H26O2: C, 75.58; H, 10.99. Found: C, 75.66;
H, 11.12.
(41) Trost, B. M.; Dyker, G.; Kulawiec, R. J . J . Am. Chem. Soc. 1990,
112, 7809-7811.
(42) Gitlesen, T.; Bauer, M.; Adlercreutz, P. Biophys. Biochim. Acta,
1345, 188-196.