4018 J. Am. Chem. Soc., Vol. 122, No. 17, 2000
Nicholas and Molinski
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Table 1. Selected H NMR Chemical Shifts (δ ppm) and Coupling Constants, J (Hz), for Pentabenzoyl Derivative 11 and Corresponding
Values of Model Compounds 6b-9b, 20, and 23b (CDCl3, 300 MHz)
For ease of comparison, the δ and J values for model compounds are aligned in columns under the locants corresponding to atom positions for
11.
CDCl3) δH 8.02 (m, 2H), 7.95 (m, 2H), 7.77 (m, 2H), 7.34-7.56 (m,
9H), 7.08 (d, J ) 8.6 Hz, 1H), 5.37 (m, 1H), 4.87 (m, 1H), 4.64 (m
1H), 4.61 (m 1H), 1.95 (m, 1H), 1.87 (m, 1H), 1.47 (m, 2H), 1.24,
0.87 (t, J ) 6.8 Hz, 3H). FABMS m/z 614.3830 [M + H]+, Calcd for
C39H52NO5 614.3845.
Experimental Section
Pentabenzoyl Derivative of Oceanapiside Aglycone (11). Oceanin
(10), the aglycone of 1, was prepared as previously described.1 Benzoyl
chloride (21 µL, 0.18 mmol) and DMAP (approximately 2 mg) were
added to a sample of 2 (4.5 mg, 9.2 µmol) in dry pyridine (1.0 mL).
The reaction was stirred at 25 °C for 9 h, at which time additional
benzoyl chloride (50 µL, 0.4 mmol) was added and the mixture heated
at 58 °C for 6 h. The mixture was treated with 1-(N,N-dimethylamino)-
3-aminopropane (75 µL, 0.6 mmol), volatiles were removed under
vacuum, and the residue was purified by chromatography (silica 25 ×
55 mm, 1:3 EtOAc/CHCl3) to give the N, N′,O,O′,O′′-pentabenzoyl
derivative 11 (2.9 mg, 31%). 1H NMR (400 MHz, CDCl3) δH 8.03 (m,
4H), 7.95 (m, 2H), 7.77 (m, 2H), 7.12 (m, 2H), 7.34-7.56 (m, 15H),
7.08 (d, J ) 8.8 Hz, 1H, NH1′), 6.38 (d, J ) 8.8 Hz, 1H, NH2′), 5.38
(m, 1H, H3), 5.21 (m, 1H, H26), 4.88 (m, 1H, H2), 4.64 (m, 1H, H1a),
4.61 (m, 1H, H1b), 4.53 (m, 1H, H27), 2.33 (m, 4H), 1.93 (m, 1H),
1.87 (m, 1H), 1.75 (m, 2H), 1.53 (m), 1.28 (d, J ) 6.7 Hz, 3H, H28),
1.25 (m). DCI (NH3) m/z 1007.5781[M + H]+, Calcd for C63H79N2O9
1007.5786.
(2S,3R)-2-(N,N-Dibenzylamino)-13-tetradecen-3-ol (21). 11-Bromo-
1-undecene (Aldrich, 200 µL, 0.91 mmol) was added to dry magnesium
turnings (135 mg, 5.5 mmol) in THF (500 µL) and heated. Additional
bromide (800 µL, 3.64 mmol) in THF (5 mL) was added slowly at a
rate to keep the mixture at reflux. After 30 min the Grignard reagent
was allowed to cool, and a portion (approximately 1.5 mL, 0.7 M
solution in THF, 1.0 mmol) was treated dropwise with a solution of
aldehyde 12 (187 mg, 0.74 mmol) in THF (2 mL). After being stirred
for 1 h, the mixture was treated with wet Et2O (2 mL) followed by sat.
aqueous NaHCO3 (5 mL) and extracted with EtOAc (×3). The
combined organic phases were washed with H2O and brine and dried
(MgSO4) before concentration to give a yellow oil. Purification of the
oil on silica gel (1:4 EtOAc/n-hexane) separated the minor (2S,3S)-
threo isomer (6.0 mg, 2%) from the major (2S,3R)-erythro isomer 21
(152.0 mg, 50%) in a ratio of 1:25. UV (MeOH) λmax 210 nm (ꢀ 20500).
[R]26D +20.8° (c 0.34, CHCl3). IR (NaCl plate, film) 3340 (br), 2924,
erythro-(2S,3S)-N,O,O-Tribenzoyl-dihydrosphingosine (20). Pal-
ladium on carbon (4 mg, 10% Pd) was added to a solution of D-erythro-
sphingosine (Sigma, 8 mg, 0.026 mmol) in MeOH (1 mL). The mixture
was evacuated-purged with H2 (×5) and left to stir under H2 (1 atm)
at 24 °C for 7.5 h. The catalyst was removed by filtration through Celite,
and the evaporation of the solvent gave D-erythro-dihydrosphingosine
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2852, 1452, 1367 cm-1. H NMR (300 MHz, CDCl3) δH 7.20-7.40
(m, 10H), 5.01 (m, 1H), 4.95 (m, 1H), 3.79 (d, J ) 13.8 Hz, 2H), 3.61
(m, 1H), 3.49 (d, J ) 13.8 Hz, 2H), 2.73 (m, 1H), 2.06 (m, 2H), 1.70
(m, 2H), 1.38, 1.27, 0.87 (d, J ) 6.6 Hz, 3H). 13C NMR (75 MHz,
CDCl3) δC 140.0 (s), 139.0 (d), 128.6 (d), 128.1 (d), 126.7 (d), 114.0
(t), 73.6 (d), 57.2 (d), 54.8 (t), 34.3 (t), 33.8 (t), 29.7 (t), 29.6 (t), 29.6
(t), 29.5 (t), 29.2 (t), 29.0 (t), 25.9 (t), 8.7 (q). HRDCI (NH3) m/z
408.3268 [M + H]+, Calcd for C28H42NO 408.3266.
(2S,3R,24R,25S)-2,25-Bis(N,N-dibenzylamino)-13-hexacosene-3,-
24-diol (22). Alkene 21 (70 mg, 0.17 mmol) in CH2Cl2 was added to
a solution of dichlorobis(tricyclohexylphosphine)benzylideneruthenium-
(IV) dichloride34 (Grubbs’s catalyst, 14 mg, 10 mol %) in CH2Cl2 (56
mM alkene). The solution initially appeared bright pink and turned
yellow/orange after approximately 10 min. The reaction was heated at
reflux for 10 h under N2 after which time no starting material could be
detected by TLC. The solvent was removed and the residue purified
by silica chromatography (1:9 EtOAc/n-hexanes) to provide dimer 22
(45.3 mg, 68%) as a 3:1 mixture of Z:E isomers. [R]26D +21.8° (c 0.6,
CHCl3). UV (MeOH) λmax 209 nm (ꢀ 33900), 258 nm (ꢀ 1400). IR
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(D-sphinganine, 4, 8.1 mg, 100%). H NMR (300 MHz, CD3OD) δH
3.71 (dd, J ) 4.2, 10.8 Hz, 1H), 3.49 (m, 1H), 3.45 (dd, J ) 7.5, 11.1
Hz, 1H), 2.70 (m, 1H), 1.2-1.6, 0.89 (t, J ) 6.3 Hz, 3H). 13C NMR
(75 MHz, CD3OD) δC 74.1, 64.4, 58.1, 34.4, 33.0, 30.7, 30.4, 27.0,
23.6, 14.3. DCIMS (NH3) found m/z 302.3060 [M + H]+, Calcd for
C18H40NO2 302.3059.
Benzoyl chloride (30 µL, 0.26 mmol) was added to a solution of 4
(8.1 mg, 0.026 mmol) and DMAP (approximately 1 mg) in pyridine
(1.5 mL). The reaction was heated at 50 °C for 5 h at which time the
pyridine was removed under vacuum, and the residue purified by flash
silica chromatography (10-20% EtOAc/n-hexane) followed by HPLC
(silica, 25 × 300 mm, 1:4 EtOAc/n-hexane, 3 mL/min) to afford
tribenzoyl derivative 20 (2.2 mg, 14%). [R]24D -26.0° (c 0.1, CHCl3).
1H NMR data25 and the optical rotation (lit.33 -26°, CHCl3) were found
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to be identical with those previously reported. H NMR (400 MHz,