1688 J . Org. Chem., Vol. 67, No. 5, 2002
Notes
26.2, 26.6, 28.0 (6C), 28.1 (2C), 29.1, 29.3, 29.5 (2C), 29.6 (2C),
29.7 (2C), 40.2, 52.1, 58.0, 83.0 (2C), 152.2 (2C), 171.7. FAB MS
m/z (%): 509 (M+ + Na, 6), 487 (M+ + 1, 76), 409 (6), 387 (26),
309 (10), 287 (100). Anal. Calcd for C26H50N2O6 (486.69): C,
64.16; H, 10.36; N, 5.76. Found: C, 64.33; H, 10.47; N, 5.51.
(14S)-14-[Bis(ter t-bu toxyca r bon yl)a m in o]-15-m eth oxy-
15-oxop en ta d eca n oic Acid (9). To a cold (0 °C), rapidly stirred
solution of 8 (1.60 mmol, 780 mg) in CH2Cl2 (2 mL) were added
a solution of 4-acetamido-TEMPO free radical (0.016 mmol, 3
mg) in CH2Cl2 (1 mL), a solution of Aliquat 336 (0.080 mmol,
32 mg) in CH2Cl2 (l mL), an aqueous solution (0.32 mL) of KBr
(0.160 mmol, 19 mg), and an aqueous solution (11.4 mL) of
NaOCl (4.00 mmol) containing NaHCO3 (4.64 mmnol, 390 mg).
After 15 min, the mixture was acidified with 10% aqueous
KHSO4 and extracted with CH2Cl2. The organic phase was dried
(Na2SO4), and the solvent was evaporated. The residue was
purified by column chromatography using a mixture of EtOAc:
6.9 Hz, CH2N3), 3.68 (s, 3H, OMe), 4.82 (dd, lH, J ) 5.2, 9.8 Hz,
CHCO); 13C NMR (50 MHz, CDCl3) δ 26.1, 26.7, 27.8 (2C), 28.0
(6C), 28.8, 29.1, 29.2, 29.4 (2C), 29.5 (2C), 29.8, 51.4, 52.1, 58.0,
82.9 (2C), 152.1 (2C), 171.5. FAB MS m/z 11 (%): 487 (3), 313
(61). Anal. Calcd for C26H48N4O6 (512.69): C, 60.91; H, 9.44; N,
10.93. Found: C, 61.20; H, 9.51; N, 10.89.
Meth yl (2S)-2-[Bis(ter t-bu toxyca r bon yl)a m in o]-15-{[(9H-
flu or en -9-ylm eth oxy)car bon yl]am in o}pen tadecan oate (13).
To a solution of 11 (1.00 mmol, 513 mg) in CH2Cl2 (10 mL) were
added 10% Pd/C (60 mg) and Fmoc-OSu (1.50 mmol, 506 mg).
The reaction mixture was stirred under H2 at room temperature
for 16 h. After filtration through a pad of Celite, the solvent was
removed and the product was purified by column chromatogra-
phy using a mixture of EtOAc:petroleum ether 2:8 as eluent.
Yield 62%; colorless oil; [R]23 -15.3 (c 0.75, CHCl3); 1H NMR
D
(200 MHz, CDCl3) δ 1.25 [br s, 20H, (CH2)10(CH2)2N], 1.49 [br s,
18H, 2 × C(CH3)3], 1.52-1.68 (m, 2H, CH2CH2N), 1.78-1.97 (m,
1H, CHHCHCO), 1.98-2.17 (m, 1H, CHHCHCO), 3.07-3.23 (m,
2H, CH2N), 3.70 (s, 3H, OMe), 4.14-4.28 (m, 1H, CHCH2O), 4.39
(d, 2H, J ) 6.8 Hz, CH2O), 4.69-4.79 (m, 1H, NH), 4.85 (dd,
1H, J ) 5.2, 9.8 Hz, CHCO), 7.23-7.45 (m, 4H, Fmoc), 7.59 (d,
2H, J ) 6.8 Hz, Fmoc), 7.76 (d, 2H, J ) 6.8 Hz, Fmoc); 13C NMR
(50 MHz, CDCl3) δ 26.1, 26.7, 27.9 (6C), 28.0 (2C), 29.3 (2C),
29.4 (2C), 29.6 (4C), 41.1, 47.1, 52.1, 58.1, 66.5, 82.9 (2C), 119.8
(2C), 125.1 (2C), 127.8 (4C), 141.3 (2C), 144.0 (2C), 152.1 (2C),
156.4, 171.6. FAB MS m/z (%): 731 (M+ + Na, 100), 631 (61),
531 (24), 509 (75). Anal. Calcd for C41H60N2O8 (708.94): C, 69.46;
H, 8.53; N, 3.95. Found: C, 69.31; H, 8.49; N, 4.13.
petroleum ether 3:7 as eluent. Yield 78%; colorless oil; [R]23
D
-25.4 (c 0.7, CHCl3); 1H NMR (200 MHz, CDCl3) δ 1.24 [br s,
18H, (CH2)9(CH2)2CO], 1.48 [br s, 18H, 2 × C(CH3)3], 1.52-1.71
(m, 2H, CH2CH2CO), 1.75-1.97 (m, 1H, CHHCHCO), 1.98-2.18
(m, 1H, CHHCHCO), 2.33 (t, 2H, J ) 7.4 Hz, CH2CO), 3.69 (s,
3H, OMe), 4.84 (dd, 1H, J ) 5.2, 9.6 Hz, CHCO); 13C NMR (50
MHz, CDCl3) δ 24.7, 26.2, 28.0 (6C), 28.1 (2C), 29.1, 29.3, 29.4
(2C), 29.6 (2C), 29.9, 34.0, 52.2, 58.1, 83.0 (2C), 152.2 (2C), 171.7,
179.6. FAB MS m/z (%): 524 (M+ + Na, 100), 446 (8), 424 (57),
324 (32), 302 (74). Anal. Calcd for C26H47NO8 (501.66): C, 62.25;
H, 9.44; N, 2.79. Found: C, 62.19; H, 9.26; N, 2.82.
Meth yl (2S)-2-[Bis(ter t-bu toxyca r bon yl)a m in o]-15-oxo-
p en ta d eca n oa te (10). To a cold (-6 °C), rapidly stirred biphasic
mixture of 8 (1.00 mmol, 488 mg), 4-acetamido-TEMPO free
radical (0.020 mmol, 4 mg), NaBr (1.00 mmol, 103 mg), toluene
(3 mL), EtOAc (3 mL), and water (0.5 mL) was added an aqueous
solution (3.14 mL) of NaOCl (1.10 mmol) containing NaHCO3
(2.90 mmol, 244 mg) dropwise over a period of 1 h. The aqueous
layer was separated and washed with EtOAc (5 mL). The
combined organic phases were washed consecutively with a
solution of KI (8 mg) dissolved in 10% aqueous KHSO4 (2 mL),
5% aq sodium thiosulfate (2 mL), and brine and dried (Na2SO4),
and the solvent was evaporated. The residue was purified by
column chromatography using a mixture of EtOAc:petroleum
(2S,5Z,13Z,17S)-2,17-Dia m in ooct a d eca -5,13-d ien ed ioic
Acid (15). The tert-butoxycarbonyl group of 14 (1.00 mmol, 769
mg) was removed by treatment with 4 N HCl in THF (25 mL)
at room temperature for 30 min. After evaporation, the residue
was dissolved in MeOH (4 mL) and treated with 1 N aqueous
NaOH (5.60 mL) under vigorous stirring at room temperature
for 1.5 h. The organic solvent was removed, and the aqueous
residue was carefully neutralized with 1 N aqueous HCl. The
product was filtered and washed with water and Et2O. Yield
77%; white solid; mp 243 °C (decomp); [R]23D +25.7 (c 0.3, AcOH);
1H NMR (200 MHz, CD3COOD) δ 1.15-1.47 [m, 8H, CHCH2-
(CH2)4CH2CH], 1.83-2.30 (m, 12H, 2 × CH2CHCO, 2 × CH2-
CHdCHCH2), 4.02-4.22 (br, 1H, 12 2 × CHCO), 5.26-5.52 (m,
2H, 2 × CHdCH). TOF MS m/z (%): 339 (M+ - 1, 100), 279
(57). Anal. Calcd for C18H32N2O4‚1.5H2O (367.49): C, 58.83; H,
9.60; N, 7.62. Found: C, 59.10; H, 9.52; N, 7.44.
Gen er a l P r oced u r e for th e P r ep a r a tion of Mosh er
Am id es of ω-Hyd r oxy Am in o Ester 7. To a stirred solution
of amino ester 7 (0.25 mmol, 80 mg) in CH2Cl2 (2.5 mL) were
added Et3N (0.60 mmol, 0.08 mL), (R)-(+)- or (S)-(-)-R-methoxy-
R-(trifluoromethyl)phenylacetic acid (0.30 mmol, 70 mg), HOBt
(0.30 mmol, 41 mg), and EDC (0.30 mmol, 58 mg) at 0 °C. The
reaction mixture was stirred at 0 °C for 30 min and at room
temperature overnight. After removal of the solvent, the product
was directly used for 19F NMR analysis.
ether 2:8 as eluent. Yield 76%; colorless oil; [R]23 -23.6 (c 1,
D
l
CHCl3); H NMR (300 MHz, CDCl3) δ 1.24 [br s, 18H, (CH2)9-
(CH2)2CO], 1.48 [br s, 18H, 2 × C(CH3)3], 1.52-1.72 (m, 2H, CH2-
CH2CO), 1.73-1.97 (m, 1H, CHHCHCO), 1.99-2.18 (m, 1H,
CHHCHCO), 2.40 (td, 2H, J ) 2.0, 7.4 Hz, CH2CO), 3.69 (s, 3H,
OMe), 4.83 (dd, 1H, J ) 5.2, 9.6 Hz, CHCO), 9.79 (t, 1H, J ) 2.0
Hz, CHO); 13C NMR (50 MHz, CDCl3) δ 22.1, 26.2, 28.0 (6C),
28.1 (2C), 29.3, 29.5 (2C), 29.6 (3C), 29.9, 44.0, 52.2, 58.0, 83.0
(2C), 152.2 (2C), 171.6, 203.0. FAB MS m/z (%): 508 (M+ + Na,
72), 429 (6), 408 (50), 308 (16), 286 (100). Anal. Calcd for C26H47
-
NO7 (485.66): C, 64.30; H, 9.75; N, 2.88. Found: C, 64.51; H,
9.69; N, 2.59.
Meth yl (2S)-15-Azid o-2-[bis(ter t-bu toxyca r bon yl)a m in o]-
p en ta d eca n oa te (11). To a stirred solution of 8 (1.60 mmol,
780 mg) in CH2Cl2 (3 mL) were added triethylamine (2.40 mmol,
0.34 mL) and methanesulfonyl chloride (2.40 mmol, 0.19 mL)
portionwise at 0 °C. The mixture was stirred at 0 °C for 30 min
and at room temperature for 30 min. The organic phase was
washed consecutively with brine, 1 M KHSO4, brine, 5% aq
NaHCO3, and brine and dried (Na2SO4), and the solvent was
removed. The mesylate was dissolved in DMF (5 mL). Sodium
azide (4.80 mmol, 312 mg) was added, and the mixture was
heated at 60 °C for 6 h. The solvent was removed, and the
residue was taken up in EtOAc (3 × 15 mL). The combined
organic phases were washed with brine, dried (Na2SO4), and
evaporated. The residue was purified by column chromatography
using a mixture of EtOAc:petroleum ether 1:9 as eluent. Yield
73%; colorless oil; [R]23D -23.4 (c 0.5, CHCl3); 1H NMR (200 MHz,
CDCl3) δ 1.23 [br s, 20H, (CH2)10(CH2)2N3], 1.49 [br s, 18H, 2 ×
C(CH3)3], 1.50-1.65 (m, 2H, CH2CH2N3), 1.71-1.95 (m, lH,
CHHCHCO), 1.97-2.16 (m, 1H, CHHCHCO), 3.23 (t, 2H, J )
Ch a r a cter istic NMR Ch em ica l Sh ifts (in p p m ). Meth yl
(2S,5Z)-2-a m in o-15-h yd r oxyp en ta d ec-5-en oa te (R)-Mosh er
a m id e: 19F NMR (188 MHz, CDCl3, reference with external
TFA) δ 8.79 (s).
Meth yl (2S,5Z)-2-a m in o-15-h yd r oxyp en ta d ec-5-en oa te
(S)-Mosh er a m id e: 19F NMR (188 MHz, CDCl3, reference with
external TFA) δ 9.18 (s).
Su p p or tin g In for m a tion Ava ila ble: Experimental pro-
cedures and analytical data for compounds 3a ,b, 4a ,b, and
5a ,b. This material is available free of charge via the Internet
at http://pubs.acs.org.
Ack n ow led gm en t. This work was partially sup-
ported by the Greek Secretariat for Research and
Technology (PENED 99 E∆ 173).
J O015768W