JOURNAL OF CHEMICAL RESEARCH 2010 237
Cu(OAc)2.H2O (400 mg) and 1 (25 mg). The mixture turned into a
dark-blue solution after stirring. Two graphite electrodes with a
constant voltage (3V) were inserted and fixed in the side-necks of
flask. The mixture was stirred and the reaction progress was monitored
by TLC. After completion (ca 3h), to the dark-blue suspension was
added aqueous HCl (5 mL, 1M) and it soon turned red. The mixture
was extracted with EtOAc (15 mL), and the organic layer was succes-
sively washed with saturated aqueous NaHCO3 (8 mL) and water
(8 mL). The organic layer was dried and evaporated, and flash
chromatography of the crude afforded product 2 (19.5 mg, 85%). M.
p. 148–149 °C1; 1H NMR (300M Hz, CDCl3)7: δ 12.60 (s,1H), 12.49
(s,1H), 7.19 (s, 2H), 7.14 (s,1H), 5.21 (1H, dd, J = 8.0, 6.8), 4.91 (1H,
dd, J = 7.2, 4.0), 2.67–2.62 (m,1H), 2.39–2.30 (m, 1H), 1.76 (s,3H),
1.64 (s, 3H)
total conversion of reactant. More interestingly, the reaction
time (100% conversion) was shortened from 10h to 3h. The
reason could be that the strong affinity between shikonin and
Cu2+ made the electrolysis reaction equilibrium shift toward
the right. Once shikonin emerged in the electrolysis, it soon
complexed Cu2+ to yield a stable compound. The electrolytic
equilibrium shifted along with the conversion of the product
shikonin. The procedure is shown in Scheme 1.
In conclusion, we have solved the problem associated with
electrolytic deprotection, which was a difficulty in the total
synthesis of shikonin. The improvement has three advantages:
first, it made the reaction complete, as practically the yield
increased from 40 to 85%; second, owing to the 100%
conversion of reactant, the isolation of shikonin became much
easier since the reactant and product were similar in polarity.
Third, the reaction time was significantly shortened from 10h
to 3h.
This work is supported by National Natural Science Founda-
tion (No. 30973604) and Key Program of Basic Research of
Shanghai (No. 08JC1410800)
Experimental
Received 3 March 2010; accepted 2 April 2010
Paper 101034 doi: 10.3184/030823410X12709960181221
Published online 30 April 2010
Reagents and solvents were obtained from commercial suppliers and
were used without further purification. All melting points were
determined on XT34 binocular microscope (Beijing Tech Instrument
1
Co., China). H NMR spectra were recorded on Mercuryplus 400
(300 MHz) spectrometer, chemical shifts were reported in parts per
million relative to tetramethylsilane. Splitting patterns were designated
as s, singlet; d, doublet; t, triplet; q, quartet; m, multiplet; br, broad.
Chemical shifts were reported in parts per million relative to the
solvent resonance as the internal standard (CDCl3, δ = 7.16 ppm).
Analytical TLC and column chromatography were performed on
silica GF254, and silica gel H60, respectively.
References
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2
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6
7
V.P. Papageorgiou, Planta Med., 1980, 38, 193.
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General procedure
Shikonin (2): To a three-necked round-bottom flask was successively
added water (2.5 mL), acetonitrile (2.5 mL), LiClO4 (530 mg),
8
9
K.C. Nicolaou and D. Hepworth, Angew. Chem. Int. Ed., 1998, 6, 37.
V.P. Papageorgiou, US Patent, No.4282250, 1981-08-04