S. E. Boiadjiev, D. A. Lightner / Tetrahedron: Asymmetry 10 (1999) 2535–2550
2547
4.7. (S,S)-3,17-Diethyl-8-(2-methoxycarbonyl-1-methylethyl)-12-(2-carboxy-1-methylethyl)-2,7,13,18-
tetramethyl-(21H,24H)-bilin-1,19-dione (12, βS,β0S-dimethylmesobiliverdin-XIIIα 8-methyl ester)
The title compound was obtained in 69% yield. For spectral data see Boiadjiev et al.20
4.8. (S)-3,17-Diethyl-8-(2-carboxyethyl)-12-(1-methylpropyl)-2,7,13,18-tetramethyl-(21H,24H)-bilin-
1,19-dione (13)
The title compound was obtained in 44% yield, mp 176–179°C. 1H NMR: δ 0.86 (3H, t, J=7.3 Hz),
1.24 (2×3H, 2×t, J=7.5 Hz), 1.32 (3H, d, J=7.0 Hz), 1.67–1.72 (2H, m), 1.83 (3H, s), 1.85 (3H, s), 2.00
(3H, s), 2.14 (3H, s), 2.15 (2H, t, J=7.5 Hz), 2.52 (2H, q, J=7.5 Hz), 2.55 (2H, q, J=7.5 Hz), 2.69 (2H, t,
J=7.5 Hz), 2.78–2.86 (1H, m), 5.95 (1H, s), 6.08 (1H, s), 6.80 (1H, s), 8.71 (2H, br. s), ∼9.3 (1H, very
br. s) ppm; and 13C NMR: δ 8.16, 8.20, 9.54, 10.29, 12.85, 14.48, 17.81, 17.85, 19.80, 20.97, 30.10,
33.25, 35.25, 97.00, 97.69, 115.03, 126.66, 127.84, 128.13, 128.62, 138.77, 139.45, 140.06, 142.47,
143.11, 146.77, 147.33, 172.71, 174.22, 176.30 ppm. HRMS (3-NBA): calcd for C34H43N4O4 (M+H)+
571.3284; found 571.3282, error 0.4 ppm, ∆0.2 mDa.
4.9. (S)-3,17-Diethyl-8-(2-carboxyethyl)-12-(2-methoxycarbonyl-1-methylethyl)-2,7,13,18-tetramethyl-
(21H,24H)-bilin-1,19-dione (14, β0S-methylmesobiliverdin-XIIIα 12-methyl ester)
The title compound was obtained in 89% yield, mp 181–183°C. 1H NMR: δ 1.22 (6H, t, J=7.5 Hz),
1.35 (3H, d, J=7.1 Hz), 1.81 (3H, s), 1.82 (3H, s), 2.02 (3H, s), 2.16 (3H, s), 2.24 (2H, t, J=7.4 Hz), 2.52
(2×2H, 2×q, J=7.5 Hz), 2.68 (2H, d, J=7.7 Hz), 2.75 (2H, t, J=7.4 Hz), 3.46–3.53 (1H, m), 3.59 (3H, s),
5.94 (1H, s), 6.01 (1H, s), 6.83 (1H, s), 8.79 (2H, br. s), ∼9.1 (1H, very br. s) ppm; and 13C NMR: δ 8.05,
8.06, 9.40, 10.24, 14.35, 17.67, 17.71, 19.65, 20.69, 27.77, 35.21, 41.11, 51.56, 97.02, 97.34, 114.96,
126.75, 127.87, 128.11, 128.63, 138.77, 138.92, 139.12, 140.04, 140.70, 142.18, 146.74, 147.08, 147.35,
172.60, 173.06, 174.04, 176.03 ppm. HRMS (3-NBA): calcd for C35H43N4O6 (M+H)+ 615.3183; found
615.3167, error 2.6 ppm, ∆1.6 mDa.
4.10. Mesobilirubin-XIIIα analogs. General procedure
To a cooled (ice bath) solution of the corresponding mesobiliverdin (0.1 mmol) in THF (10 mL) and
CH3OH (30 mL, both dry and deoxygenated) was added NaBH4 (378 mg, 10 mmol) over 15 min under
N2. The cooling bath was removed and after a further 30 min of stirring, the yellow green mixture was
diluted with ice/water (100 mL) and acidified with CH3COOH. The product was extracted with CHCl3
(4×50 mL), washed with H2O (3×70 mL), dried over anhydrous Na2SO4, filtered, and the solvent was
evaporated under vacuum. The crude material was purified by preparative TLC (3% CH3OH/CH2Cl2) or
radial chromatography on silica gel (1–3% CH3OH/CH2Cl2 v/v). The isolated yellow pure mesobilirubin
fraction was recrystallized from CHCl3/CH3OH.
4.11. (S)-3,17-Diethyl-8-(2-carboxyethyl)-12-(2-carboxy-1-methylethyl)-2,7,13,18-tetramethyl-
(10H,21H,23H,24H)-bilin-1,19-dione (1, β0S-methylmesobilirubin-XIIIα)
The mesobilirubin 2 (61.7 mg, 0.1 mmol) was dissolved in THF:CH3OH=1:1 (30 mL, both deoxyge-
nated) and 5 mL of 1 M aqueous NaOH was added. The mixture was stirred under N2 at 50°C for 3 h.
The THF and CH3OH solvents were evaporated under vacuum, water (100 mL) was added followed by
7 mL of CH3COOH and 1–2 mL of 2% HCl (pH<7), and the product was extracted with CHCl3 (3×25