HETEROCYCLES, Vol. 61, 2003
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To an ice-cooled solution of alcohol (400 mg, 1.50 mmol) in CH2Cl2 (15 mL) was added Dess-Martin
periodinane (1.91 g, 4.49 mmol) and the mixture was stirred at rt for 6 h. The reaction mixture was
poured into saturated Na2SO3 and extracted with CH2Cl2. The organic layer was washed with water,
saturated NaHCO3 and brine, dried over MgSO4 and concentrated in vacuo. The residue was purified by
flash column chromatography on silica gel (EtOAc:hexane = 1:1) to afford ketone (236 mg, 60%) as a
colorless oil: [a]D28 = –203° (c = 1.37, CHCl3); IR (film, cm-1) n 1780 (s, C=O), 1630-1680 (s, NCO); 1H
NMR (300 MHz, CDCl3) d = 1.3-1.45 (2H, m), 1.5-1.7 (2H, m), 1.64 (3H, d, J = 4.8 Hz), 1.84 (3H, s),
1.95-2.05 (2H, m), 2.2-2.4 (2H, m), 2.65-2.8 (2H, m), 3.61 (1H, ddd, J = 7.2, 8.7, 11.4 Hz), 4.12 (1H, m),
5.03 (1H, s), 5.3-5.5 (2H, m).
To an ice-cooled solution of the corresponding ketone (165 mg, 0.63 mmol) in MeOH (10 mL) were
added NaOAc (129 mg, 1.57 mmol) and NH2OH•HCl (87.1 mg, 1.25 mmol) and the mixture was stirred
at rt for 3 h. Then the reaction mixture was poured into water and extracted with CH2Cl2. The organic
layer was washed with water, saturated NaHCO3 and brine, dried over MgSO4 and concentrated in vacuo.
The residue was purified by flash column chromatography on silica gel (EtOAc:hexane = 1:1) to afford
(–)-1 [E:Z = 46% (81 mg) : 24% (42 mg)] as colorless crystal.
(–)-Brevioxime (1): mp 147-149ºC; [a]D22 = –209° (c 0.26, CHCl3); 1H NMR (300 MHz, CDCl3) d = 1.3-
1.4 (2H, m), 1.5-1.6 (2H, m), 1.63 (3H, d, J = 4.5 Hz), 1.83 (3H, s), 1.85-2.0 (2H, m), 2.2-2.4 (2H, m),
2.8-3.0 (2H, m), 3.48 (1H, dt, J = 8.1, 11.4 Hz), 4.07 (1H, ddd, J = 3.6, 9.3, 11.4 Hz), 5.3-5.4 (2H, m),
13
5.56 (1H, s), 8.79 (1H, s); C-NMR (75 MHz, CDCl3) d =10.1, 17.9, 23.8, 26.2, 29.1, 30.6, 32.2, 41.7,
84.1, 107.0, 125.2, 130.8, 157.7, 163.4, 163.9; HRMS m/z [MH+] 279.1669 (calcd for C15H23N2O3
279.1708).
1
Z-Isomer of (–)-Brevioxime: H NMR (300 MHz, CDCl3) d = 1.35-1.4 (2H, m), 1.5-1.6 (2H, m), 1.6-
1.65 (3H, m), 1.83 (3H, s), 1.9-2.0 (3H, m), 2.15-2.45 (2H, m), 2.70 (1H, ddd, J = 1.8, 7.5, 9.6 Hz), 2.84
(1H, m), 3.34 (1H, ddd, J = 7.5, 9.6, 11.1 Hz), 5.3-5.5 (2H, m), 5.82 and 5.83 (1H, s), 9.0 (1H, brs); 13C-
NMR (75 MHz, CDCl3) d = 10.0, 17.9, 26.3, 27.1, 29.0, 30.5, 32.2, 41.5, 79.8, 106.7, 125.1, 130.9, 156.2,
163.3, 164.2.
(R)-[(E,E) and (E,Z)]-2-(5-Heptenyl)6,7-dihydro-3-methyl-4H-pyrrolo[2,1-b][1,3]oxazine-4,8(8aH)-
dione 8-oxime [(+)-Brevioxime (1) and Z-Isomer of (+)-Brevioxime]
In the same manner as above, 13 (3.30 g, 6.53 mmol) was treated with TBAF to afford alcohol (14, 1.54 g,
89%) as colorless oil: [a]D23 = +110° (c 1.06, CHCl3); IR (film, cm-1) n = 1780 (s, C=O), 1630-1680 (s,
1
NCO); H NMR (300 MHz, CDCl3) d = 1.5-1.6 (2H, m), 1.25-1.4 (2H, m), 1.65 (3H, m), 1.79 (3H, s),
1.5-2.0 (3H, m), 2.15-2.35 (3H, m), 3.6 (2H, m), 4.48 (1H, m), 5.03 (1H, d, J = 3.6 Hz), 5.3-5.5 (2H, m).
In the same manner as above, 14 (175 mg, 0.67 mmol) was oxidized to afford ketone (233 mg, 94%) as