33.14, 33.49, 37.26, 48.58, 48.86, 49.00, 49.28, 49.43, 54.30,
67.19, 69.81, 72.09, 73.16, 73.96, 101.35, 131.51, 134.97,
176.08; Mass spectrum (ESIMS), m/z
5.2.20. (2R, 3R, 4E)-2-Azido-1-O-benzoyloxy-octadec-4-
ene-3-ol (22). In a round bottom flask, (2R, 3R, 4E)-2-azido-3-O-
benzoyloxy-1-O-triisopropylsilyloxy-octadec-4-ene (0.138 g,
0.236 mmol) was dissolved in THF (3.5 mL) and cooled to 0 °C.
After cooling, 1M TBAF (0.637 mL, 0.637 mmol) was added
drop-wise and the reaction was allowed to come to room
temperature. The reaction was stirred at this temperature for 10
minutes under N2 atmosphere. The reaction was monitored by
thin layer chromatography using 4:1 hexanes-ethyl acetate. Upon
completion, the reaction was quenched with sat. aq. NaHCO3.
The aqueous layer was then extracted with ethyl acetate (4x) and
the extracts were combined, washed with brine, dried (MgSO4),
and concentrated under reduced pressure. The concentrated crude
product was loaded onto silica and any remaining solvent was
evaporated under reduced pressure. The dry slurry was purified
by flash column chromatography (22 x 2.5 cm) on silica gel (230
x 400 mesh). Elution was with 9:1 hexanes-ethyl acetate. The
product fractions were combined, concentrated, and then dried
under reduced pressure to provide a colorless oil. Yield = 99.0
=
706.7 [M+Na]+
C40H77NO7Na requires 707.0.
5.2.18. (2R,
3R,
4E)-3-O-Alloxycarbonyloxy-1,2-O-
isopropylideneoctadec-4-ene-1,2-diol (20). In a round bottom
flask, (2R, 3R, 4E)-1,2-O-isopropylideneoctadec-4-ene-1,2,3-triol
(0.232 g, 0.681 mmol) was dissolved in
a dry 3:2
CH2Cl2:pyridine mixture (10 mL) and cooled to -10 °C. After
cooling, allyl chloroformate (0.253 mL, 2.38 mmol) was added
drop-wise. The solution was stirred at this temperature for 2
hours under N2 atmosphere. The reaction was monitored by thin
layer chromatography using 4:1 hexanes-ethyl acetate. Upon
completion, the reaction was quenched with MeOH and
concentrated under reduced pressure. The concentrated crude
product was loaded onto silica and any remaining solvent was
evaporated under reduced pressure. The dry slurry was purified
by flash column chromatography (15 x 2 cm) on silica gel (230 x
400 mesh). Elution was with 9.5:0.5 hexanes-ethyl acetate. The
product fractions were combined, concentrated, and then dried
under reduced pressure to provide a colorless oil. Yield = 0.261 g
mg (78.0%); TLC R = 0.15 (4:1 hexanes-ethyl acetate); 1H NMR
f
(CDCl3, 600 MHz): δ 0.89 (t, 3H, CH3, J = 7.2 Hz), 1.26-1.1.32
(m, 20H, 10CH2), 1.39 (m, 2H, CH=CHCH2CH2), 2.08 (m, 2H,
CH=CHCH2), 2.29 (d, 1H, OH, J = 3.6 Hz ), 3.83 (m, 1H,
CHN3), 4.26 (m, 1H, CHOH), 4.42 (m, 1H, BzOCH2), 4.56 (m,
1H, BzOCH2), 5.57 (d.d, 1H, CH=CHCH2, J = 7.2, 15.0 Hz),
5.84 (d.t, 1H, CH=CHCH2, J = 7.8, 15.3 Hz), 7.47 (t, 2H, Ph, J =
7.8 Hz), 7.59 (t, 1H, Ph, J = 7.8 Hz), 8.08 (d, 2H, Ph, J = 8.4);
13C NMR (CDCl3, 400 MHz): δ 14.3, 22.9, 29.1, 29.4, 29.5, 29.7,
29.8, 29.84, 29.85, 29.87, 29.88, 32.1, 32.5, 64.5, 65.2, 72.8,
127.6, 128.7, 129.8, 130.0, 133.5, 136.5, 166.5; Mass spectrum
(ESIMS), m/z = 452.5 [M+Na]+ C25H39N3O3Na requires 452.6.
1
(93.3%); TLC Rf = 0.64 (4:1 hexanes-ethyl acetate); H NMR
(CDCl3, 600 MHz): δ 0.88 (t, 3H, CH3, J = 7.2 Hz), 1.24-1.33
(m, 22H, 11CH2), 1.36 (s, 3 H, CH3CCH3), 1.44 (s, 3 H,
CH3CCH3), 2.05 (m, 2H, CH=CHCH2), 3.74 (d.d, 1H, OCH2, J
= 6.6, 8.4 Hz), 3.98 (d.d, 1H, OCH2, J = 7.8, 8.4 Hz), 4.22 (m,
1H, OCHCH2), 4.62 (m, 2H, OCH2CH=CH2), 5.06 (d.d, 1H,
CHOAlloc, J = 7.8, 7.8 Hz), 5.26 (d, 1H, OCH2CH=CH2, J =
10.2 Hz), 5.34-5.39 (m, 2H, OCH2CH=CH2, CH=CHCH2), 5.89-
5.97 (m, 2H, OCH2CH=CH2, CH=CHCH2); 13C NMR (CDCl3,
400 MHz): δ 14.3, 22.8, 25.6, 26.6, 28.4, 28.8, 29.2, 29.4, 29.5,
29.58, 29.6, 29.7, 29.81, 29.82, 29.84, 32.1, 32.5, 56.5, 65.9,
68.6, 77.5, 80.5, 110.4, 118.9, 123.3, 131.7, 139.0, 154.4; Mass
spectrum (HRMS), m/z = 447.4 [M+Na]+ C25H44O5Na requires
447.6.
5.2.21.
(2S,3R,E)-2-palmitamido-1-
((triisopropylsilyl)oxy)octadec-4-en-3-yl benzoate (23).16 In a
round bottom flask, (2R, 3R, 4E)-2-Azido-3-O-benzoyloxy-1-O-
triisopropylsilyloxy-octadec-4-ene (100.0 mg, 0.1708 mmol) was
dissolved in THF (4 mL). After dissolution, triphenylphosphine
(134.0 mg, 0.5124 mmol) and H2O (61.5 µL) were added, and the
reaction was heated to 45 °C with a cold-water condenser under
N2 atmosphere. The reaction was stirred at this temperature for
3.5 hours. The reaction was monitored by thin layer
chromatography using 9.5:0.5 hexanes-ethyl acetate. Upon
completion, the reaction mixture was quenched with Et3N and
filtered through Celite. The filtrate was concentrated and co-
evaporated with toluene (1x) and used for further reaction
without purification. The crude product was dissolved in dry
CH2Cl2. After dissolution, HOBt (34.0 mg, 0.222 mmol),
EDC·HCl (42.56 mg, 0.222 mmol), palmitic acid (43.8 mg,
0.1708 mmol), and Et3N (35.73 µL, 0.2562 mmol) were added to
the solution. The reaction mixture was stirred under N2
atmosphere at room temperature for 7 hours. The reaction was
monitored by thin layer chromatography using 9.5:0.5 hexanes-
ethyl acetate. After completion, the solution was concentrated
under reduced pressure. The concentrated crude product was
loaded onto silica and any remaining solvent was evaporated
under reduced pressure. The dry slurry was purified by flash
column chromatography (15 x 2 cm) on silica gel (230 x 400
5.2.19. (2R, 3R, 4E)-2,3-O-Carbonate-octadec-4-ene-1,2,3-
triol (21). In
a round bottom flask, (2R, 3R, 4E)-3-O-
alloxycarbonyloxy-1,2-O-isopropylideneoctadec-4-ene-1,2-diol
(0.255 g, 0.621 mmol) was dissolved in a 1:1 THF:H2O mixture
(3 mL) and cooled to 0 °C. After cooling, glacial acetic acid (4.5
mL) was added drop-wise. The solution was then heated to 55 °C
and stirred for 12 hours with a water-cooled reflux condenser.
The reaction was monitored by thin layer chromatography using
4:1 hexanes-ethyl acetate. Upon completion, the reaction was
quenched with saturated aq. NaHCO3 and extracted with ethyl
acetate (3x). The extracts were combined, dried (MgSO4), and
concentrated under reduced pressure. The concentrated crude
product was loaded onto silica and any remaining solvent was
evaporated under reduced pressure. The dry slurry was purified
by flash column chromatography (15 x 2.5 cm) on silica gel (230
x 400 mesh). Elution was with 4:1 hexanes-ethyl acetate. The
product fractions were combined, concentrated, and then dried
under reduced pressure to provide an off-white solid. Yield =
129.0 mg (63.6%); TLC R = 0.05 (4:1 hexanes-ethyl acetate); 1H
f
NMR (CDCl3, 600 MHz): δ 0.89 (t, 3H, CH3, J = 7.2 Hz), 1.26-
1.32 (m, 20H, 10CH2), 1.40 (m, 2H, CH=CHCH2CH2), 1.95 (d.d,
1H, OH, J = 6.0, 7.8 Hz), 2.11 (m, 2H, CH=CHCH2), 3.70 (m,
1H, HOCH2), 4.00 (m, 1H, HOCH2), 4.38 (m, 1H,
HOCH2CHOC=O), 5.00 (d.d, 1H, OCHCH=CH, J = 7.8, 7.8 Hz),
5.52 (d.d, 1H, CH=CHCH2, J = 7.8, 15.0 Hz), 5.97 (d.t, 1H,
CH=CHCH2, J = 7.8, 15.3 Hz); 13C NMR (CDCl3, 400 MHz): δ
14.3, 22.9, 28.7, 29.3, 29.5, 29.6, 29.7, 29.8, 32.1, 32.3, 60.4,
79.4, 82.4, 123.9, 140.6, 155.2; Mass spectrum (HRMS), m/z =
349.2352 [M+Na]+ C19H34O4Na requires 349.2355.
→5% ethyl acetate in hexanes. The
mesh). Elution was with 1
product fractions were combined, concentrated, and then dried
under reduced pressure to provide a colorless gel. Yield = 64.0
mg (45.8% over two steps); TLC Rf = 0.17 (9.5:0.5 hexanes-ethyl
acetate); Mass spectrum (HRMS), m/z = 820.6636 [M+Na]+
C50H87NO4SiNa requires 820.6615.
5.2.22.
N-((2S,3R,E)-1,3-dihydroxyoctadec-4-en-2-
yl)palmitamide (24).16 In a round bottom flask, (2S,3R,E)-2-