2286
M. T. Huggins, D. A. Lightner / Tetrahedron 57 (2001) 2279±2287
The reaction mixture was cooled to room temperature, taken
up in dichloromethane, and washed with water and sat. aq.
sodium bicarbonate solution. The organic extract was dried
over Na2SO4 (anhydr.), and the solvent was removed (roto-
vap). The residue was puri®ed by radial chromatography
(97:3 by vol. CH2Cl2/MeOH) and recrystallized from abs
ethanol to give 3 (48 mg) in 93% yield. It had mp 136±
13C NMR, it was dif®cult to remove water and traces of
eicosanedioic acid completely. It had mp 144±1468C; IR
1
(KBr) n 3347, 3229, 1707, 1654 cm21; H NMR (DMSO-
d6, 500 MHz) d 1.22 (m, 28H), 1.48 (m, 4H), 1.76 (s, 3H),
1.84 (s, 3H), 2.00 (s, 3H), 2.04 (s, 3H), 2.17 (t, 7.0 Hz, 2H),
2.49 (t, 7.0 Hz, 2H), 5.92 (s, 1H), 9.78 (s, 1H), 10.10 (s, 1H),
11.89 (s, 1H) ppm; 1H NMR (CDCl3, 500 MHz) d 1.30 (m,
28H), 1.62 (m, 2H), 1.70 (m, 2H), 1.90 (s, 3H), 1.94 (s, 3H),
2.10 (s, 3H), 2.11 (s, 3H), 2.38 (t, 7.5 Hz, 2H), 2.64 (t,
7.5 Hz, 2H), 6.12 (s, 1H), 8.95 (s, 1H), 10.75 (s, 1H),
13.22 (s, 1H) ppm; 13C NMR data are in Table 1; and
UV±visible data are in Table 4; FAB-HRMS (3-
NBA1PEG400): calcd for C33H54N2O3 [M1z] 526.4134;
found 526.4132, error 0.5 ppm, D 0.8 mDa.
1378C; IR (KBr) n 3348, 3152, 2861, 1736, 1666 cm21
;
1H NMR (CDCl3, 500 MHz) d 1.26 (m, 10H), 1.59 (m,
2H), 1.64 (m, 2H), 1.93 (s, 3H), 1.96 (s, 3H), 2.11 (s, 3H),
2.13 (s, 3H), 2.28 (t, 7.5 Hz, 2H), 2.74 (t, 7.5 Hz, 2H), 3.65
1
(s, 3H), 6.13 (s, 1H), 10.18 (s, 1H), 11.34 (s, 1H) ppm; H
NMR (DMSO-d6, 500 MHz) d 1.23 (m, 10H), 1.48 (m, 4H),
1.75 (s, 3H), 1.84 (s, 3H), 1.99 (s, 3H), 2.04 (s, 3H), 2.26 (t,
7.5 Hz, 2H), 4.50 (t, 7.5 Hz, 2H), 3.56 (s, 3H), 5.91 (s, 1H),
9.81 (s, 1H), 10.10 (s, 1H) ppm; 13C NMR are in Table 1;
and UV±visible data are in Table 4. Anal. Calcd for
C24H36N2O3 (400.6): C, 71.96; H, 9.06; N, 6.99. Found: C,
71.90; H, 8.97; N, 7.20.
4.1.6.
9-(19-Carbomethoxynonadecyl)-2,3,7,8-tetra-
methyl-(10H)-dipyrrin-1-one (4). Dipyrrinone (2)
(56 mg, 0.1 mmol) and 50 mL of methanol were added to
a 100 mL round-bottom ¯ask equipped for magnetic
stirring. Five milliliters of 10% aq. H2SO4 was added to
the solution dropwise over 5 min, and the reaction mixture
was heated at re¯ux for 1 h. The reaction mixture was
cooled to room temperature, taken up in dichloromethane
(50 mL), and washed with water and sat. aq. sodium
bicarbonate solution. The organic extract was dried over
Na2SO4 (anhydr.), and the solvent was removed (rotovap).
The residue was puri®ed by radial chromatography (97:3 by
vol. CH2Cl2/MeOH) and recrystallized from methanol±
water to give 4 (52 mg) in 91% yield. Although the sample
gave excellent 13C NMR, it was dif®cult to remove water
completely. It had mp 147±1488C; IR (KBr) n 3348, 3156,
2870, 1741, 1673 cm21; 1H NMR (CDCl3, 500 MHz) d 1.23
(m, 30H), 1.61 (m, 4H), 1.93 (s, 3H), 1.95 (s, 3H), 2.02 (s,
3H), 2.12 (s, 3H), 2.24 (t, 7.5 Hz, 2H), 2.73 (t, 7.5 Hz, 2H),
3.66 (s, 3H), 6.12 (s, 1H), 10.06 (s, 1H), 11.17 (s, 1H) ppm;
1H NMR (DMSO-d6, 500 MHz) d 1.21 (m, 30H), 1.50 (m,
4H), 1.76 (s, 3H), 1.84 (s, 3H), 1.99 (s, 3H), 2.04 (s, 3H),
2.21 (t, 7.5 Hz, 2H), 2.26 (t, 7.5 Hz, 2H), 3.56 (s, 3H), 5.91
(s, 1H), 9.79 (s, 1H), 10.09 (s, 1H) ppm; 13C NMR data are
in Table 1; and UV±visible data are in Table 4; FAB-HRMS
(3-NBA1PEG400): calcd for C34H56N2O3 [M1z] 540.4291;
found 544.4240, error 1.2 ppm, D 0.8 mDa.
4.1.5.
9-(19-Carboxynonadecyl)-2,3,7,8-tetramethyl-
(10H)-dipyrrin-1-one (2). (a) Eicosanedioic acid (0.50 g,
1.46 mmol) was heated at re¯ux in thionyl chloride (15 mL)
for 1 h. Excess thionyl chloride was removed by distillation
at water aspirator pressure, and 10 mL of dry CCl4 was
added to the crude acid chloride. The CCl4 was removed
by distillation at water aspirator pressure, and the process
repeated. The residue was added to a solution of dipyrrinone
8 (79 mg, 0.37 mmol) in 150 mL in a 250 mL round-bottom
¯ask. Anhydrous stannic chloride (5.0 g, 0.37 mmol) was
added, and the mixture was stirred for 16 h at room tempera-
ture. The reaction mixture was then poured into a mixture of
conc. HCl (200 mL) and 100 g of ice and stirred for 2 h. The
organic layer was separated, and the aqueous layer was
extracted with dichloromethane. The combined extracts
were washed with sat. aq. NaHCO3, water, and dried over
Na2SO4 (anhydr.). The solvent was removed (rotovap),
and the crude product was puri®ed to afford 9-(19-carboxy-
nonadecanoyl)-2,3,7,8-tetramethyl-(10H)-dipyrrinone (6)
(119 mg, 60%). The product 6 was unusually insoluble in
nonpolar organic solvents and contained signi®cant
amounts of eicosanoic acid, which had similar solubility
properties. Consequently, 6 was reduced directly to 2. The
spectral data relevant to 6 are: IR (KBr) n 3316, 2927, 2850,
1
1695, 1675 cm21; H NMR (DMSO-d6, 500 MHz) d 1.27
Acknowledgements
(m, 24H), 1.29 (m, 4H), 1.46 (m, 2H), 1.57 (m, 2H), 1.79 (s,
3H), 2.01 (s, 3H), 2.07 (s, 3H), 2.18 (t, 7.5 Hz, 2H), 2.21 (s,
3H), 2.78 (t, 7.5 Hz, 2H), 5.95 (s, 1H), 10.34 (s, 1H), 10.72
(s, 1H), 11.92 (s, 1H) ppm.
We thank the US National Institutes of Health (HD-17779)
for generous support of this work. Michael T. Huggins is an
R. C. Fuson Graduate Fellow. Special thanks are accorded
to Prof. T. W. Bell for use of the VPO instrument.
(b) Dipyrrinone (6) (55 mg, 0.1 mmol) and 50 mL of 2-
propanol were placed in a 100 mL round-bottom ¯ask
equipped for magnetic stirring. Sodium borohydride
(100 mg, 1.7 mmol) was added, and the reaction mixture
was heated at re¯ux for 3 h. The hot reaction mixture was
poured into 100 mL of ice water, and the solution was acidi-
®ed with 10% aq. HCl. The suspension was extracted with
dichloromethane, and the combined organic extracts were
washed with water and dried over Na2SO4 (anhydr.). The
solvent was removed (rotovap), and the crude product was
puri®ed by radial chromatography (97:3 by vol. CH2Cl2/
MeOH) and recrystallized from CH2Cl2±hexane to give
48 mg (89%) of 2. Although the sample gave excellent
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