A Continuous Production of Norcantharidin Analogues
Letters in Drug Design & Discovery, 2011, Vol. 8, No. 6 573
Advance AMX 300 MHz spectrometer at 300.13 and 75.48
MHz, respectively. Chemical shifts are relative to TMS as
internal standard. All compounds returned satisfactory Mass
spectra were obtained using a micromass liquid chromatog-
raphy Z-path (LCZ) platform spectrometer. Mass to charge
ratios (m/z) are stated with their peak intensity as apercent-
age in parentheses. All mass spectra were obtained via the
ES method thus fragmentation patterns were not observed.
The University of Wollongong, Australia, Biomolecular
Mass Spectrometry Laboratory, analysed samples for
HRMS. The spectra were run on a micromass QTof2 spec-
trometer using polyethylene glycol or polypropylene glycol
as the internal standard.
(1S,4R)-3-(Benzylcarbamoyl)-7-oxabicyclo[2.2.1]heptane-
2-carboxylic acid (20)
1H NMR (DMSO-d6) (300 MHz): ꢀ 7.97 (t, J = 5.7 Hz,
1H), 7.62-7.59 (m, 1H), 7.43-7.37 (m, 2H), 7.31-7.23 (m,
2H), 4.73 (s, 1H), 4.49 (d, J = 4.1 Hz, 1H), 4.28-4.14 (m,
2H), 2.95 (d, J = 9.6 Hz, 1H), 2.85 (d, J = 9.6 Hz, 1H), 1.63-
1.41 (m, 4H); 13C NMR (DMSO-d6) (75 MHz): ꢀ 173.0,
172.2, 130.9, 128.1, 127.6, 126.2, 78.9, 77.1, 53.1, 51.9,
42.4, 28.0, 27.7; MP 170°C [8].
ACKNOWLEDGEMENTS
The authors acknowledge the financial support of the
Australian Research Council and the Australian Cancer Re-
search and Ramaciotti Foundations. MT acknowledges the
UNI-PRS postgraduate funding from the University of New-
castle. KAY acknowledges John Morris Scientific (Austra-
lia) for generous scholarship provision. SNM and EU ac-
knowledge the Lambton High School Work Experience re-
lease program.
In a Typical Synthesis of Acid-Ester Analogues [18]
A mixture of 5,6-dehydronorcantharidin (5) (0.05 M in
methanol) was stirred until dissolved. The corresponding
solution was then passed through the H-cube flow hydro-
genation apparatus under the conditions of 50 bar, 50°C, 1
mL/min, controlled H2, 10% Pd/C. The reaction eluant was
collected, and the solvent removed in vacuo to leave a white
solid which did not require further purification.
(1S,4R)-3-(Methoxycarbonyl)-7-oxabicyclo[2.2.1]heptane-
2-carboxylic acid (6)
1H NMR (acetone-d6) (300 MHz): ꢀ 4.78-4.77 (m, 2H),
3.55 (s, 3H), 3.10-3.00 (m, 2H), 1.70-1.55 (m, 4H); 13C
NMR (acetone-d6) (75 MHz): ꢀ 170.9, 170.7, 77.8, 77.4,
51.5, 50.9, 50.1, 28.2, 27.2; MP 140-141°C [18].
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(1S,4R)-3-(4-Methoxybenzylcarbamoyl)-7-
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1H NMR (DMSO-d6) (300 MHz): ꢀ 7.68 (t, J = 5.5 Hz,
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