12 as a colorless oil: [R]20D ) -2.8 (c 5.0, CH2Cl2); IR (KBr, cm-1
)
(8S,9S,10R)-9,13-Dihydroxy-8-methoxy-10,12-dimethyl-
trideca-6,11-dienoic Acid 1:
νmax ) 3418, 2930, 1754, 1455, 1367, 1151, 1032; 1H NMR
(CDCl3, 400 MHz) δ 5.68 (dt, J ) 15.4, 6.8 Hz, 1H), 5.27 (dd, br,
J ) 15.6, 8.2 Hz, 1H), 4.74 (dd, J ) 32.2, 6.7 Hz, 2H), 3.63 (dd,
J ) 7.46, 3.08 Hz, 1H), 3.48 (t, J ) 6.8 Hz, 2H), 3.39 (s, 3H),
3.22 (s, 3H), 3.16 (t, J ) 6.8 Hz, 1H), 2.18 (t, J ) 7.3 Hz, 2H),
2.16 (q, J ) 7.0 Hz, 2H), 1.83 (m, 1H), 1.55 (m, 2H), 1.40 (s,
9H), 1.39 (m, 2H), 0.78 (d, J ) 6.9 Hz); 13C NMR (CDCl3, 100
MHz) δ 173.0, 135.6, 126.7, 98.8, 84.8, 80.5, 80.0, 64.6, 56.0, 55.8,
36.5, 35.2, 31.9, 28.4, 28.0, 24.5, 10.2; HRMS calcd for C19H36O6
(M + Na)+ 383.2404, found 383.2403.
(8S,9S,10R)-13-Hydroxy-8-methoxy-9-methoxymethoxy-
10,12-dimethyltrideca-6,11-dienoic Acid tert-Butyl Ester
16. To a solution of the diester 15 (0.076 g, 0.172 mmol) in THF
(2.5 mL) at room temperature was added MeOH (0.017 mL,
0.430 mmol) followed by LiBH4 (0.22 mL, 0.430 mmol, 2.0 M
solution in toluene). The reaction was stirred for 6 h, whereupon
it was quenched with silica gel (0.5 g). Purification of the
resulting slurry by column chromatography (ethyl acetate/
hexane, 2:3, v/v) provided 0.033 g (48%) of alcohol 16 as a
colorless oil: 1H NMR (CDCl3, 400 MHz) δ 5.60 (dt, J ) 15.4,
6.7 Hz, 1H), 5.27 (dd, br, J ) 15.8, 7.9 Hz, 1H), 4.58 (d, J ) 6.8
Hz, 1H), 4.65 (d, J ) 6.8 Hz, 1H), 3.89 (s, 3H), 3.46 (dd, J ) 8.2,
2.4 Hz, 1H), 3.33 (s, 3H), 3.18 (t, J ) 5.3 Hz, 1H), 3.13 (s, 3H),
2.69 (m, 1H), 2.33 (s, br, 1H), 2.14 (t, J ) 7.3 Hz, 2H), 2.02 (q,
J ) 7.0 Hz, 2H), 1.59 (d, J ) 0.9 Hz, 3H), 1.51 (m, 2H), 1.35 (s,
9H), 1.34 (m, 2H), 0.90 (d, J ) 6.8 Hz, 3H); 13C NMR (CDCl3,
100 MHz) δ 172.8, 134.6, 134.1, 128.8, 127.7, 98.2, 84.8, 83.4,
79.8, 68.4, 56.0, 55.8, 35.1, 33.6, 31.8, 28.4, 27.9, 24.4, 15.6, 13.6;
HRMS calcd for C22H40O6 (M + Na)+ 423.2717, found 423.2713.
To a 5:2 solution of THF/[HCl] (0.5 mL) at room temperature
was added the ester 16, and the mixture was stirred for 20 h
whereupon it was quenched with saturated aqueous NaHCO3
(2.0 mL), washed with ethyl acetate (2 × 4.0 mL), and reacidified
with 1 N HCl to pH ) 4. The aqueous layer was then extracted
with ethyl acetate (2 × 4.0 mL), dried with Na2SO4, and
concentrated under reduce pressure. The resulting oil was
further purified by flash chromatography (acetone/hexane, 1:1,
v/v) to give 3.4 mg (34%) of the title compound 1 as a colorless
(8S,9S,10R)-8-Methoxy-9-methoxymethoxy-10,12-dimeth-
yltrideca-6,11-dienedioic Acid 13-tert-Butyl Ester 1-Ethyl
Ester 15:
(8S,9S,10R)-8-Methoxy-9-methoxymethoxy-10-methyl-
11-oxoundec-6-enoic Acid tert-Butyl Ester 13. To a solution
of alcohol 12 (1.46 g, 4.05 mmol) in CH2Cl2 (50 mL) was added
DMP (2.03 g, 4.80 mmol). After 1 h, the solvent was removed in
vacuo. Purification of the oily white solid by silica gel chroma-
tography (1:1 hexane/ethyl acetate) gave 1.25 g (86%) of aldehyde
13 as a colorless oil: 1H NMR (CDCl3, 400 MHz) δ 9.74 (s, 1H),
6.70 (dd, J ) 10.7, 1.4 Hz, 1H), 5.68 (dt, J ) 15.5, 6.8 Hz, 1H),
5.32 (dd, br, J ) 15.6, 8.2 Hz, 1H), 4.70 (dd, J ) 32.0, 6.9 Hz,
2H), 3.91 (t, J ) 4.57, 1H), 3.58 (dd, J ) 8.3, 5.07, 1H), 3.31 (s,
3H), 3.18 (s, 3H), 2.57 (m, 1H), 2.18 (t, J ) 7.5, 2H), 2.08 (q,
J ) 7.5, 2H), 1.55 (m, 2H), 1.41 (s, 9H), 1.40 (m, 2H), 1.04 (d,
J ) 6.9 Hz, 3H); 13C NMR (CDCl3, 100 MHz) δ 202.8, 172.9,
136.1, 126.5, 97.6, 82.6, 80.6, 80.0, 56.2, 55.9, 48.2, 35.3, 32.0,
28.4, 28.1, 24.5, 8.72; HRMS calcd for C19H34O6 (M + Na)+
381.2247, found 381.2240; HRMS calcd for C19H34O6 (M + Na)+
381.2247, found 381.2240.
oil: [R]20 ) +1.3 (c 5.0, CH2Cl2); IR (KBr, cm-1) νmax ) 2932,
D
To a solution of aldehyde 13 (0.44 g, 0.994 mmol) in 1,2-
dichloroethane (10 mL) at room temperature was added carb-
ethoxyethylidene triphenylphosphorane (1.08 g, 2.98 mmol). The
resulting yellow solution was heated to 60 °C for 18 h, at which
time TLC showed only partial conversion to the diester 15. More
carbethoxyethylidenetriphenylphosphorane (1.08 g, 2.98 mmol)
was added, and reaction was stirred for an additional 18 h at
60 °C whereupon it was concentrated under reduced pressure
and by flash chromatography (ethyl acetate/hexane, 1:4, v/v) to
afford 0.29 g (66%) of diester 15 as a colorless oil: [R]20D ) +5.4
(c 1.0, CH2Cl2); IR (KBr, cm-1) νmax ) 2974, 2935, 1730,1706,
1649, 1453, 1367, 1252, 1151, 1026; 1H NMR (CDCl3, 400 MHz)
δ 6.70 (dd, J ) 10.7, 1.4 Hz, 1H), 5.68 (dt, J ) 15.5, 6.8 Hz, 1H),
5.32 (dd, br, J ) 15.6, 8.2 Hz, 1H), 4.70 (dd, J ) 32.0, 6.9 Hz,
2H), 4.18 (q, J ) 7.11 Hz, 2H), 3.48 (dd, J ) 8.18, 4.86 Hz, 1H),
3.98 (s, 3H), 3.33 (t, J ) 6.3 Hz, 1H), 3.19 (s, 3H), 2.85 (m, 1H),
2.20 (t, J ) 7.3 Hz, 2H), 2.08 (q, J ) 7.2 Hz, 2H), 1.82 (d, J )
2.3 Hz), 1.57 (m, 2H), 1.42 (s, 9H), 1.41 (m, 2H), 1.25 (t, J ) 7.1
Hz, 3H), 1.03 (d, J ) 6.8 Hz, 3H); 13C NMR (CDCl3, 100 MHz)
δ 173.0, 168.3, 144.4, 135.2, 127.5, 127.0, 98.3, 83.7, 80.0, 60.5,
56.3, 35.3, 35.0, 32.0, 28.5, 28.1, 24.6, 15.0, 14.3, 12.5; HRMS
calcd for C24H42O7 (M + Na)+ 465.2823, found 465.2822.
1731, 1454, 1371, 1241, 1155, 1109; 1H NMR (CD3OD), 400 MHz)
δ 5.71 (dt, J ) 15.4, 6.7 Hz, 1H), 5.45 (dd, br, J ) 15.5, 8.6 Hz,
1H), 5.29 (dq, J ) 10.0, 1.3 Hz, 1H), 3.92 (s, br, 2H), 3.49 (dd,
J ) 8.6, 4.1 Hz, 1H), 3.19 (s, 3H), 3.17 (dd, J ) 7.0, 4.2 Hz, 1H),
2.71 (m, 1H), 2.29 (t, J ) 7.3 Hz, 2H), 2.12 (q, J ) 7.0 Hz, 2H),
1.67 (d, J ) 1.3 Hz, 3H), 1.62 (m, 2H), 1.45 (m, 2H), 0.97 (d,
J ) 6.7 Hz, 3H); 13C NMR (CD3OD, 100 MHz) δ 177.6, 138.4,
136.8, 130.0, 129.5, 84.7, 79.2, 68.9, 66.3, 35.8, 34.8, 33.1, 29.8,
25.6, 16.3, 14.0; HRMS calcd for C16H28O5 (M + Na)+ 323.1829,
found 323.1827.
Acknowledgment. We thank Dr. Marco Biamonte
for his help in running NMR experiments and assigning
the protons of some advance intermediates in the
synthesis.
Supporting Information Available: Experimental pro-
cedures, HRMS, and 1H and 13C NMR spectra for 4, 6-8, 10-
14, and 16-19. This material is available free of charge via
JO050942S
J. Org. Chem, Vol. 70, No. 20, 2005 8215