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DOI: 10.1055/s-2006-944190
Total Synthesis of Pterosines B and C via a Photochemical Key Step
Publikationsverlauf
Publikationsdatum:
12. Juni 2006 (online)
Abstract
A total synthesis of pterosines B and C is reported. Starting with a fourfold substituted benzene derivative, the introduction of the remaining substituents is mainly based on Sonogashira couplings followed by different transformations of the ethyne moiety. The key step is a photochemical ring-closure of an α-mesyloxy ketone forming the 1-indanone skeleton.
Key words
total synthesis - photochemistry - arenes - ketones
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4-(Carboxymethyl)-3,5-dimethylbenzoic Acid (10).
Compound 9 (1.00 g, 3.78 mmol) in 10 mL dry THF was cooled to 0 °C and 6.8 mL (6.8 mmol, 1.8 equiv) 1 M BH3-THF solution was dropped in slowly. After stirring at 0 °C for 2 h a mixture of 10 mL (0.02 mol, 5 equiv) 2 M NaOH and 5 mL (0.06 mol, 15 equiv) aq H2O2 solution (30%) was added. After additional stirring for 2 h further 20 mL of 1 M NaOH and 50 mL of Et2O were added. The phases were separated and the aqueous phase was extracted several times with Et2O. Then the aqueous phase was acidified to pH 1 with HCl and the product was extracted with several portions of Et2O. The combined organic phases were dried and evaporated, giving 350 mg (1.68 mmol, 44%) of 10 as a white solid; mp 285 °C. 1H NMR (300 MHz, DMSO-d 6): δ = 2.29 (s, 6 H, 3,5-Me), 3.65 (s, 2 H, CH2), 7.59 (s, 2 H, CHarom). 13C NMR (75 MHz, DMSO-d 6): δ = 19.8 (3,5-Me), 35.2 (CH2), 128.5 (CHarom), 128.8, 137.3, 137.9 (Cq), 167.4, 171.8 (COOH). IR (KBr): 2959 (br s), 2923 (s), 2858 (s), 1718 (s), 1667 (s), 1425 (s), 1413 (s), 1303 (s), 1244 (s), 1230 (s), 1182 (m). HRMS (ESI): m/z calcd for C11H13O4 [MH+]: 209.0808. Found: 209.0809. - 13
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References and Notes
Irradiation of 17a and 17b.
For solvents, conditions and yields see Table
[1]
. The irradiation was performed in a 500 mL reactor vessel, equipped with a 150 W high-pressure mercury arc lamp (TQ 150, Heraeus) and monitored by TLC. The solvent was removed in vacuo and the residue was purified by flash chromatography.
Analytical Data for 2-(4,6-Dimethyl-3-oxo-2,3-dihydro-1
H
-inden-5-yl)ethyl Acetate (
18a).
Mp 39-41 °C. 1H NMR (300 MHz, CDCl3): δ = 2.03 (s, 3 H, CH3-acetate), 2.42 (s, 3 H, Me-Carom), 2.60-2.64 (m, 2 H, 2-CH2), 2.67 (s, 3 H, Me-Carom), 2.94-2.98 (m, 2 H, 3-CH2), 3.03 (t, J
3 = 7.7 Hz, 2 H, CH2CH2O), 4.12 (t, J
3 = 7.7 Hz, 2 H, CH2CH2O), 7.10 (s, 1 H, CHarom). 13C NMR (75 MHz, CDCl3): δ = 13.6, 21.0 (CH3-Carom), 21.1 (CH3-acetate), 24.6 (3-CH2), 27.8 (CH2CH2O), 37.1 (2-CH2), 62.7 (CH2CH2O), 125.9 (CHarom), 132.9, 133.8, 137.8, 140.1, 154.6 (Cq), 171.0 (COOR), 207.8 (RCOR).
Analytical Data for 2-{1-[(Pivaloyl)oxy]-4,6-dimethyl-3-oxo-2,3-dihydro-1
H
-inden-5-yl}ethyl Pivalate (
18b).
1H NMR (300 MHz, CDCl3): δ = 1.14, 1.17 (s, 9 H, Piv), 2.46 (s, 3H, Me-Carom), 2.51 (dd, J
3 = 3.0 Hz, J
2 = 18.8 Hz, 1 H, CH2CH), 2.68 (s, 3 H, Me-Carom), 3.03 (t, J
3 = 7.7 Hz, 2 H, CH2CH2O), 3.08 (dd, J
3 = 7.1 Hz, J
2 = 18.8 Hz, 1 H, CH2CH), 4.10 (t, J
3 = 7.7 Hz, 2 H, CH2CH2O), 6.15 (dd, J
3 = 3.0 Hz, J
3 = 7.1 Hz, 1 H, CHOPiv), 7.19 (s, 1 H, CHarom). 13C NMR (75 MHz, CDCl3): δ = 13.8, 21.3 (CH3-Carom), 27.0, 27.1 (CH3, Piv), 28.0 (CH2CH2O), 38.6, 38.6 (Cq, Piv), 44.6 (2-CH2), 62.3 (CH2CH2O), 68.5 (3-CH), 73.2 (CH2O), 125.4 (CHarom), 132.8, 136.7, 137.5, 145.1, 151.0 (Cq), 178.5, 178.6 (COOR), 202.9 (RCOR). IR (film): 2973 (s), 1717 (vs), 1599 (s), 1478 (s), 1458 (s), 1396 (s), 1281 (s), 1148 (s), 1033 (s), 1010 (s), 984 (m). HRMS (ESI): m/z calcd for C23H33O5 [MH+]: 389.2323; found: 389.2324.
Experimental Procedure for 3-Hydroxy-6-(2-hydroxyethyl)-5,7-dimethyl-1-indanone (
22).
To a solution of 65 mg (0.17 mmol) 18b in 10 mL DMSO was added a mixture of 100 mL 0.01 M aq HEPES buffer solution (pH 7.5, I = 0.1 M NaCl) and 90 mg (2160 units) porcine liver esterase (EC 3.1.1.1, Sigma). The mixture was stirred 2 d at r.t. in which the reaction course was monitored by HPLC analysis (see below). After complete saponification of both ester groups the mixture was treated with 50 mL CH2Cl2, filtrated and the phases were separated. The organic phase was dried with MgSO4, evaporated and purified by FCC (CH2Cl2-MeOH, 10:1, R
f
= 0.39) affording 20.0 mg (90.8 mol, 54%) 22 as a white solid.
HPLC conditions: column: Eurospher 100 C-18 (Knauer), 5 µm, 250 × 4 mm; mobile phase: gradient MeOH-H2O (70:30 → 90:10) linear in 20 min, then 90:10 flow: 1 mL/min. peaks: t
R(22) = 2.6 min, t
R(18b) = 31.9 min.
Mp 143-145 °C. 1H NMR (300 MHz, DMSO-d
6): δ = 2.34 (dd, J
3 = 3.0 Hz, J
2 = 18.5 Hz, 1 H, CH2CH), 2.40, 2.56 (s, 3 H, Me-Carom), 2.84 (t, J
3 = 7.5 Hz, 2 H, CH2CH2OH), 2.90 (dd, J
3 = 7.0 Hz, J
2 = 18.5 Hz, 1 H, CH2CH), 3.41-3.46 (m, 2 H, CH2CH2OH), 4.78 (t, J
3 = 5.5 Hz, 1 H, CH2OH), 5.02-5.06 (m, 1 H, 3-CH), 5.57 (d, J
3 = 6.0 Hz, 1 H, OH), 7.31 (s, 1 H, CHarom). 13C NMR (75 MHz, DMSO-d
6): δ = 13.3, 21.0 (CH3-Carom), 32.1 (CH2CH2OH), 47.7 (2-CH2), 59.8 (CH2CH2OH), 65.6 (3-CH), 125.0 (CHarom), 131.5, 135.6, 137.1, 144.2, 155.6 (Cq), 204.3 (RCOR). IR (KBr): 3391 (br s), 2923 (m), 1687 (vs), 1596 (s), 1408 (m), 1326 (m), 1308 (s), 1260 (m), 1065 (s), 1025 (s), 804 (m). HRMS (ESI): m/z calcd for C13H17O3 [MH+]: 221.1172; found: 221.1173.