Vidya et al.
6.75-6.68 (dt, J ) 7, 15 Hz, 1H), 5.98-5.96 (br d, J ) 7 Hz,
1H), 5.82-5.78 (d, J ) 15 Hz, 1H), 5.73-5.65 (m, 1H), 5.39-
5.34 (app q, J ) 7 Hz, 1H), 5.06-5.01 (m, 2H), 4.94-4.89 (app
q, J ) 6 Hz, 1H), 4.18-4.15 (dd, J ) 4, 9 Hz, 1H), 3.77 (s, 3H),
3.64-3.59 (m, 1H), 3.53-3.48 (m, 1H), 3.15-3.10 (dd, J ) 6,
14 Hz, 1H), 3.08-2.99 (m, 2H), 2.97-2.91 (dd, J ) 7, 14 Hz,
1H), 2.43-2.39 (m, J ) 7 Hz, 3H), 1.80-1.73 (m, 1H), 1.62-
1.55 (ddd, J ) 5, 9, 13 Hz, 1H), 1.47-1.41 (ddd, J ) 4, 9, 13
Hz, 1H), 0.99-0.98 (d, J ) 7 Hz, 3H), 0.91-0.89 (d, J ) 7 Hz,
3H), 0.90-0.88 (d, J ) 7 Hz, 3H), 0.88 (s, 9H), 0.04 (s, 3H),
0.01 (s, 3H); 13C NMR δ 173.8, 169.5, 164.7, 164.2, 158.8, 140.1,
138.6, 130.3 (2C), 127.2, 125.6, 116.3, 114.0 (2C), 75.4, 70.7,
55.2, 54.5, 44.3, 40.8, 36.7, 36.6, 36.0, 34.0, 25.7 (3C), 24.1,
23.4, 21.7, 18.2, 16.3, -4.7, -5.4; MS (EI) m/z 629 (M+); HRMS
(FAB, m/z) calcd for C34H52N2O7Si 629.3622, found 629.3622.
7.09 (d, J ) 8.6 Hz, 2H), 7.05-7.02 (t, J ) 5.5 Hz, 1H), 6.81-
6.78 (d, J ) 8.6 Hz, 2H), 6.73-6.66 (ddd, J ) 4.7, 10, 15 Hz,
1H), 6.41-6.37 (d, J ) 16 Hz, 1H), 6.03-5.96 (dd, J ) 8.8, 16
Hz, 1H), 5.77-5.75 (d, J ) 7.9 Hz, 1H), 5.75-5.71 (d, J ) 15
Hz, 1H), 5.06-5.01 (ddd, J ) 2, 6.6, 11 Hz, 1H), 4.91-4.88
(dd, J ) 3.6, 10 Hz, 1H), 4.73-4.67 (m, 1H), 3.76 (s, 3H), 3.54-
3.48 (m, 1H), 3.46-3.39 (m, 1H), 3.15-3.11 (dd, J ) 6, 14 Hz,
1H), 3.04-2.98 (dd, J ) 7.5, 14 Hz, 1H), 2.57-2.52 (m, 3H),
2.39-2.30 (m, 1H), 1.78-1.57 (m, 3H), 1.35-1.27 (m, 1H),
1.13-1.11 (d, J ) 6.8 Hz, 3H), 0.73-0.72 (d, J ) 6.4 Hz, 3H),
0.70-0.69 (d, J ) 6.4 Hz, 3H); 13C NMR δ 172.8, 170.9, 170.8,
165.6, 158.5, 141.7, 136.7, 131.8, 130.2 (2C), 128.6 (2C), 128.5,
127.5, 126.1 (2C), 125.0, 114.1 (2C), 76.6, 71.5, 55.2, 54.3, 42.2,
39.7, 36.4, 35.2, 34.2, 32.4, 24.3, 22.6, 21.2, 17.2; MS (FAB)
m/z 591.3 (M+ + H); HRMS (FAB, m/z) calcd for C34H43N2O4
(M+ + H) 591.3070, found 591.3069.
(3E)-4-(N-{(1R)-2-(3,3-Dim eth yl-2-oxoa zetid in yl)-1-[(4-
m eth oxyp h en yl)m eth yl]-2-oxoeth yl}ca r ba m oyl)-1-((1R)-
1-m et h ylp r op -2-en yl)-(1S)-b u t -3-en yl-(2S)-2-h yd r oxy-4-
m eth ylp en ta n oa te (5a ). The silyl ether 13 (6.0 mg, 9.5 µmol)
was dissolved in CHCl3 (1 mL, dried over activated 4 Å
molecular sieves). BF3‚Et2O (10 µL, 76.3 µmol) was added via
syringe. After 1 h, CHCl3 (5 mL) and saturated aqueous
NaHCO3 (2 mL) were added. The organic layers were dried
(MgSO4), filtered, and concentrated to provide clean 5a as an
oil (4.4 mg, 88%). 1H NMR δ 7.10-7.08 (d, J ) 9 Hz, 2H), 6.83-
6.81 (d, J ) 9 Hz, 2H), 6.71-6.63 (dt, J ) 7, 15 Hz, 1H), 6.07-
6.05 (br d, J ) 7 Hz, 1H), 5.81-5.77 (d, J ) 15 Hz, 1H), 5.71-
5.62 (ddd, J ) 8, 10, 17 Hz, 1H), 5.36-5.33 (app q, J ) 6 Hz,
1H), 5.08-5.02 (m, 2H), 4.97-4.93 (app q, J ) 6 Hz, 1H), 4.14-
4.12 (br s, 1H), 3.77 (s, 3H), 3.64-3.61 (m, 1H), 3.54-3.49 (m,
1H), 3.16-3.11 (dd, J ) 6, 14 Hz, 1H), 3.08-3.03 (m, 2H),
2.95-2.90 (dd, J ) 8, 14 Hz, 1H), 2.45-2.40 (m, 3H), 1.91-
1.84 (m, 1H), 1.52-1.48 (m, 2H), 1.00-0.99 (d, J ) 6.9 Hz,
3H), 0.95-0.93 (d, J ) 7 Hz, 3H), 0.94-0.92 (d, J ) 7 Hz, 3H);
13C NMR δ 175.4, 169.6, 164.9, 164.3, 158.8, 139.7, 138.4, 130.3
(2C), 127.2, 125.8, 116.6, 114.0 (2C), 76.4, 69.0, 55.2, 54.6, 43.5,
41.1, 36.6 (2C), 36.0, 34.1, 24.5, 23.3, 21.4, 16.2.
Ar en a sta tin A (2). Olefin 15 (5.0 mg, 8.5 µmol) was reacted
as previously reported40 with dimethyldioxirane57 to obtain a
2:1 mixture (de was determined by HPLC Phenomenex Hy-
persil 5µ, C18, 150 × 3.2 mm, 254 nm, 3:2 CH3CN:H2O, 0.5
mL/min, retention time â ) 7.2 min, R ) 7.9 min) of epoxide
diastereomers (3.9 mg, 76%). [R]D +37 (c 0.10, CHCl3).40
ter t-Bu tyl (2E,7E)-5-[(2S)-4-Meth yl-2-(1,1,2,2-tetr a m e-
th yl-1-silapr opoxy)pen tan oyloxy]-(5S,6R)-6-m eth yl-8-ph e-
n yloct a -2,7-d ien oa t e (16). To alcohol 6b 41 (181 mg, 0.599
mmol) in CH2Cl2 (3 mL) at 0 °C under a nitrogen atmosphere
were added DMAP (370 mg, 3.028 mmol) and triethylamine
(0.43 mL, 3.052 mmol). To the above solution was added acid
chloride 7 (5 equiv), obtained from bis-TBS protected L-leucic
acid,55 in CH2Cl2 (6 mL) dropwise at 0 °C. After 10 min the
solution was brought to room temperature and stirred for 2
h. The reaction mixture was diluted with excess CH2Cl2 and
washed with water, saturated bicarbonate solution, and brine,
dried over sodium sulfate, filtered, and concentrated. The
residue was purified by flash column chromatography (5%
ethyl acetate-hexanes) to provide 16 (292 mg, 92%) as a
colorless oil. [R]D +19 (c 2.4, CHCl3); IR (film) 2957, 2857, 1751,
1
Dep h en yld esep oxya r en a sta tin A (14). Alcohol 5a (4.4
mg, 8.6 µmol) was dissolved in CH2Cl2 (2 mL). Bu4NCN (21
mg, 77.0 µmol) was dissolved in CH2Cl2 (2 mL) and both were
stirred with flame-activated crushed 4 Å molecular sieves for
1 h. The Bu4NCN solution was transferred via syringe drop-
wise to the solution of 5a . After 16 h, the reaction was filtered
through Celite and concentrated. Column chromatography (50:
50 to 75:25 EtOAc:hexanes) provided clean product 14 (3.0 mg,
1715, 1151 cm-1; H NMR δ 7.37-7.23 (m, 5H), 6.80 (dt, 1H,
J ) 7.4, 15 Hz), 6.43 (d, 1H, J ) 16 Hz), 6.08 (dd, 1H, J ) 8.5,
16 Hz), 5.82 (d, 1H, J ) 14 Hz), 5.10-5.05 (m, 1H), 4.21 (dd,
1H, J ) 4.0, 9.2 Hz), 2.66-2.60 (m, 1H), 2.51-2.47 (m, 2H),
1.82-1.71 (m, 1H), 1.57 (ddd, 1H, J ) 4.6, 9.2, 14 Hz), 1.49 (s,
9H), 1.44 (ddd, 1H, J ) 5.2, 9.4, 14 Hz), 1.13 (d, 3H, J ) 6.8
Hz), 0.92 (s, 9H), 0.88 (d, 3H, J ) 6.5 Hz), 0.82 (d, 3H, J ) 6.7
Hz), 0.09 (s, 3H), 0.05 (s, 3H); 13C NMR δ 174.4, 165.8, 142.6,
137.4, 132.0, 130.7, 128.9 (2C), 127.8, 126.6 (2C), 126.4, 80.7,
75.9, 71.0, 44.8, 41.3, 34.8, 28.5 (3C), 26.1 (3C), 24.4, 23.7, 21.9,
18.6, 17.2, -4.2, -4.9; MS (FAB+, NBA) m/z 531.4 (M+ + H);
1
68%). IR (film) 3420, 3300, 2990, 1740, 1675, 1525 cm-1; H
NMR δ 7.11-7.09 (d, J ) 8.6 Hz, 2H), 7.05-7.02 (t, J ) 5.7
Hz, 1H), 6.81-6.79 (d, J ) 8.6 Hz, 2H), 6.71-6.63 (ddd, J )
5, 10, 15 Hz, 1H), 5.84-5.82 (d, J ) 8 Hz, 1H), 5.75-5.71 (d,
J ) 14 Hz, 1H), 5.69-5.65 (m, 1H), 5.08 (br s, 1H), 5.05-5.04
(d, J ) 6 Hz, 1H), 5.02-4.97 (ddd, J ) 2, 5, 11 Hz, 1H), 4.94-
4.91 (dd, J ) 4, 9.5 Hz, 1H), 4.72-4.66 (m, 1H), 3.76 (s, 3H),
3.54-3.47 (m, 1H), 3.47-3.40 (m, 1H), 3.16-3.11 (dd, J ) 6,
14 Hz, 1H), 3.03-2.97 (dd, J ) 7.6, 14 Hz, 1H), 2.44-2.28 (m,
2H), 1.76-1.66 (m, 1H), 1.48-1.40 (m, 1H), 1.04-1.02 (d, J )
7 Hz, 3H), 0.92-0.90 (d, J ) 6.4 Hz, 3H), 0.88-0.87 (d, J )
6.4 Hz, 3H); 13C NMR δ 172.8, 170.82, 170.76, 165.7, 158.5,
141.8, 138.6, 130.2 (2C), 128.5, 124.9, 116.5, 114.1 (2C), 76.8,
71.4, 55.2, 54.3, 42.4, 39.8, 36.1, 35.2, 34.2, 32.5, 24.5, 22.9,
21.5, 16.6; MS (FAB) m/z 515.3 (M+ + H); HRMS (FAB, m/z)
calcd for C28H39O7N2 (M+ + H) 515.2757, found 515.2775.
HRMS (FAB, m/z) calcd for
548.3771, found 548.3765.
C
31H54N1O5Si1 (M+ + NH4)
N-{(1R)-2-(3,3-Dim eth yl-2-oxoa zetid in yl)-1-[(4-m eth ox-
yp h en yl)m et h yl]-2-oxoet h yl}(ter t-b u t oxy)ca r b oxa m id e
(20). To the tyrosine derivative 1836 (221 mg, 0.748 mmol) in
acetonitrile (4 mL) at 0 °C was added DIEA (0.5 mL, 2.993
mmol) under a nitrogen atmosphere, followed by HBTU (625
mg, 1.646 mmol). To this mixture was added lactam 1960-62
(114 mg, 1.122 mmol) in acetonitrile (6 mL) and the solution
was stirred at room temperature for 5 h. The reaction was
quenched with saturated NH4Cl solution and the compound
was extracted with ethyl acetate (3 × 20 mL). The combined
organic layers were washed with water and brine, dried over
sodium sulfate, filtered, and concentrated. Flash column
chromatography (20% ethyl acetate-hexanes) of the crude
material afforded Boc-protected N-acylazetidinone 20 (256 mg,
91%) as a colorless crystalline solid. Mp 112-113 °C; [R]D
Desep oxya r en a sta tin A (15).40,41 Olefin 14 (17 mg, 33
µmol) was dissolved in CH3CN (0.33 mL) in a dry sealed tube.
The solution was flushed with argon and iodobenzene (4.0 mL,
36 µmol), Pd(OAc)2 (1.1 mg, 5.0 µmol), and TEA (46 mL, 330
µmol) were added. The tube was sealed and placed in a 80-
85 °C oil bath with vigorous stirring overnight. After 20 h,
the solution was filtered and purified by silica gel chromatog-
raphy to obtain product 15 as a solid (3 mg, 31% based on
recovered starting material) and unreacted starting material
14 (6 mg). [R]D +27 (c 0.80, CHCl3); IR (film) 3365, 3260, 2940,
-37.5 (c 1.46, CHCl3); IR (film) 3365, 1789, 1712, 1513 cm-1
;
1H NMR δ 7.11 (d, 2H, J ) 8.2 Hz), 6.79 (d, 2H, J ) 8.5 Hz),
5.22 (br d, 1H, J ) 7.3 Hz), 5.07 (br d, 1H, J ) 4.2 Hz), 3.73
(s, 3H), 3.36 (1/2 ABq, 1H, J ) 7.2 Hz), 3.21 (1/2 ABq, 1H, J )
7.2 Hz), 3.03-2.98 (m, 1H), 2.88-2.82 (m, 1H), 1.36 (s, 9H),
1.30 (s, 3H), 1.22 (s, 3H); 13C NMR δ 171.2, 159.0 (2C), 155.4,
130.9 (2C), 128.0, 114.2 (2C), 80.1, 56.3, 55.6, 51.7, 50.3, 38.1,
1
1725, 1710, 1665 cm-1; H NMR δ 7.33-7.15 (m, 5H), 7.11-
9692 J . Org. Chem., Vol. 68, No. 25, 2003